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Xpress Fat Loss Workouts Summary

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Contents: Ebooks, Training Program
Author: Nicholas Ong
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Highly Recommended

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Resting Metabolic Rate

The resting metabolic rate (RMR) is the energy expended by an individual who is resting but awake and fasted in comfortable ambient conditions. RMR, which includes the energy cost of maintaining the integrated systems of the body and the homeothermic temperature at rest, accounts for approx 60 to 70 of daily energy expenditure in sedentary adults (8) and is therefore the largest component of TDEE. There is a close relationship between RMR and body size this association has led to the development of widely used equations to predict RMR from height and weight (43-47). Three-quarters of the variation in RMR is determined by fat-free mass (48) and, to a lesser extent, by fat mass, gender, and age. Together, these four components explain 80 to 85 of the interindividual variance in RMR. Some of the remaining variance can be further explained by family membership therefore, genetic factors probably contribute (48,49). Interestingly, RMR adjusted for differences in fat-free mass, fat mass,...

Low Metabolic Rate

Obesity is associated with a high absolute metabolic rate, both in resting conditions and over 24 h (8,78), and therefore, cannot be caused by a low absolute metabolic rate, as is often proposed. Many investigators who have studied energy expenditure in humans have suggested that when a clear defect in energy expenditure is lacking in obese individuals, obesity can be only the result of excessive energy intake. It is important to note, however, that there is wide variability in the relationship between metabolic rate and body size, suggesting that, at any given body size, individuals can have high, normal, or low relative metabolic rates. Studies in adult nondiabetic Pima Indians found that a low relative metabolic rate (resting and 24-h) adjusted for differences in fat-free mass, fat mass, age, and sex was a risk factor for body weight gain (79). Specifically, 4 yr of follow-up in the same individuals identified that the risk of gaining 10 kg in body weight was approx 8 times greater...

Alterations in Carbohydrate Metabolism

The inflammatory response induces a metabolic state characterized by increased gluconeogenesis secondary to cytokine upregulation of the rate-limiting enzyme phospho-enolpyruvate carboxykinase118 even when exogenous carbohydrate intake is adequate. Serum levels of insulin, glucagon, and corticosteroids are all increased. The metabolic result is a syndrome of hyperinsulinemia, insulin resistance,119 depressed glycogenesis and fat catabolism,120 and enhanced peripheral glucose uptake and utilization. Precursor amino acids are deam-inated, the nitrogen is converted to urea (which is excreted in urine), and the glucose derived from the carbon backbone is oxidized for energy.

The Modification of the Endocrine System of Domestic Animals

The animals had an elevated basal metabolic rate and an associated high cardiac output, IGF-1 was elevated, and renal function was impaired. Bone growth was abnormal, particularly in the front limbs, and the internal organs of the transgenic sheep were significantly larger than controls. The animals showed obvious symptoms of diabetes, and all died within one year of birth.

Distribution of Cannabinoid Receptors

CB1 receptors are among the most abundant G protein-coupled receptors in the brain, having similar densities as receptors for GABA and glutamate-gated ion channels (5,9). The distribution of CB1 receptors in the central nervous system is heterogeneous, with higher densities in the basal ganglia, hippocampus, and cerebellum (10). Although CB1 expression in the hypothalamus, a key integrative area in the regulation of energy homeostasis, is relatively low, activation of hypothalamic CB1 has profound effects (9). Within the brain, CB1 receptors are expressed by glial astrocytes as well as by neurons (11). Activation of CB1 on astrocytes increases available energy to local neuronal circuits, and the administration of cannabinoid agonists increases overall energy metabolism in the brain (12).

Classification of Diabetes Mellitus

Type 2 diabetes is a more heterogeneous disease compared to type 1 diabetes. Most subjects with type 2 diabetes have a condition called insulin resistance. This is a state in which more than normal amounts of insulin are needed to produce a normal metabolic response to insulin.22 Insulin resistance is asymptomatic and may be found in subjects years before they develop type 2 diabetes.2324 As long as the pancreas is able to secrete increased amounts of insulin to counter the reduced response to insulin, blood glucose levels stay within the normal range in individuals with insulin resistance. If the pancreas is unable to keep up with the demand for higher insulin secretion rates, blood glucose concentrations start to rise and diabetes may ensue. Biochemical investigation has shown that insulin concentrations are higher than normal in subjects with insulin resistance and are normal in patients with type 2 diabetes of short duration.25 Thus, patients with type 2 diabetes have relative...

Thyroid Function Tests

Thyroxine (T4) is the most abundant thyroid hormone secreted by thyroid follicular cells. Thyroxine increases the body's metabolic rate, sensitizes the cardiovascular system in order to increase cardiac output, stimulates cellular differentiation, affects the maturation of the skeletal and central nervous systems, and is involved in other physiological processes.

Monocyte Chemoattractant Protein1

In summary, MCP-1 is a cytokine that is thought to promote macrophage recruitment into AT. The chronically elevated levels of insulin that are often seen with obesity may promote the synthesis and secretion of MCP-1 from adipocytes. Though more research is needed, these higher levels of MCP-1 may then have distinct metabolic effects, possibly contributing to the development of metabolic disease.

Gestation Lactation And Maternal Environment

To separate out the independent effects of genotype, obesity, and diet on offspring, we used rats that were selectively bred from the outbred Sprague-Dawley strain to be either prone or resistant to the development of diet-induced obesity (DIO) on a moderate (high-energy HE ) fat diet (50). Similar to the inheritance of much human obesity (21), the DIO and diet-resistant (DR) phenotypes are also inherited as polygenic traits (43,50,51). On a low-fat diet, DIO and DR rats are both lean. However, when the caloric density and fat content of the diet are increased, only DIO rats become obese, hyperinsulinemic, glucose-intolerant, hypertensive, and hyperlipidemic on the HE diet (50,52-55). The phenotype of the DIO and DR rats has remained stable for more than 35 generations (50,55), making these rats ideal for the separating the genetic from dietary factors influencing the development of obesity in offspring. When DIO dams were made obese on an HE diet throughout gestation and lactation,...

Postnatal Influences on Offspring

Both leptin and insulin can affect development during the postnatal period. Rat pups are born relatively undeveloped as compared with human infants. They have little body fat and produce very little leptin over the first 7 to 10 d of life (142). Depending on the doses given, pups may (90,143,144) or may not (89) respond to exogenous leptin administration by reducing their weight gain or adiposity during this period. It is likely that leptin given during this early postnatal period primarily increases metabolic rate rather than reducing food intake (145). Elevated leptin levels in the milk of obese dams might alter the metabolism of their pups through a similar mechanism, as leptin can be absorbed from the milk and enter the circulation of the pup during this early postnatal period (146-149). When leptin is administered orally to pups at 4 d of age, it not only reduces their adiposity and brown adipose tissue thermogenic capacity but also decreases their endogenous production of leptin...

And Protection During CEA

Regional anaesthesia is advocated by some clinicians because of the possibility of continuous neurological assessment and less haemodynamic instability. Disadvantages may include restlessness, anxiety and discomfort. It is well recognized that general anaesthetics have the ability to protect the brain during ischaemic conditions, mainly by decreasing oxygen demand (cerebral metabolic rate). Hypotension and tachycardia are frequent during general anaesthesia and often the administration of ai-adrenergic agonists such as phenylephrine is required, which in turn can lead to myocardial ischaemia.

Potential Explanations For The Antiobesity Effect Of A Vegetarian Diet

Vegetarian diets tend to contain significantly more carbohydrates, particularly complex carbohydrates. A high carbohydrate meal may actually speed up the resting metabolic rate, while a high fat meal seems to have little effect on metabolism. There is some evidence that overfeeding with carbohydrates but not with fat provokes an insulin-mediated ther-mogenesis that acts to retard weight gain.34 Toth and Poehlman35 found that young male vegetarians had an 11 higher resting metabolic rate than non-vegetarians in spite of similar energy intakes. The major dietary difference between the two groups was an increased ingestion of carbohydrate and a reduction in fat intake by the vegetarians. Restricting fat, however, is certainly not the total answer to the problem of obesity. In fact, Hervey-Bernio in a recent study indicated that those on a calorie-restricted program lose twice as much weight as those who simply restrict their fat intake.45 The quality and type of fat may also be...

In Vivo Antiplasmodial Activity

However, there are a number of caveats to consider. First, mice may not metabolise neem extracts in the same way as humans. Human metabolism may convert inactive compounds into active metabolites. Thus, trimethoprim is ineffective against murine malaria, but effective in humans.

Components Of Energy Expenditure And Their Relevance To Obesity

Total daily energy expenditure (TDEE) varies substantially in humans (42) such that two adults of the same size could have an EE that varies by 1500 kcal d. The largest determinants of TDEE are weight, height, age, and gender (42). Whereas both weight and height are positive determinants of TDEE, age is a negative predictor in adults. Across all ages, TDEE is approx 11 higher in males, after adjustments for body size (42). With the increasing prevalence of obesity, understanding the inherent interindividual variation in TDEE is important. The variability in daily energy requirements is related to the variability in the energy expended in its three major components resting metabolic rate, diet-induced thermogenesis, and activity thermogenesis (Fig. 2).

Activity Thermogenesis

Als exhibit a range of physical activity, which represents only 20 to 30 of total energy expenditure. Reduced physical activity as a cause of obesity is an obvious and attractive hypothesis. The energy expended in physical activity is quite variable, and the worldwide increase in obesity parallels the increase in sedentary lifestyles (66). However, until the introduction of the DLW method for measuring energy expenditure in free-living conditions (18,67), there has been no satisfactory method by which to assess the impact of physical activity on TDEE in humans. An increasing database of DLW in more than 1000 individuals confirms the wide variability in total energy expenditure in adults and children alike and, therefore, in physical activity (42,68-70). In a review of 574 DLW measurements, Black et al. compiled data to (1) establish the extremes of sustainable human energy expenditure (2) establish the average and range of habitual energy expenditure in relationship to age and sex and...

Energy Expenditure In The Etiology Of Obesity

Cross-sectional studies that compare lean and obese individuals have added little to our understanding of the physiological mechanisms predisposing to weight gain (76). An understanding of the etiology of human obesity demands longitudinal studies to reveal predictors or risk factors. Several studies have prospectively examined these predictors in the Pima Indian population in southwestern Arizona, a population where obesity is extremely prevalent (77) and, therefore, weight gain is common in young adults. In these individuals at least six metabolic parameters have been found to be predictive of weight gain. In particular, related to energy expenditure and relevant to understanding the etiology of obesity, are low metabolic rate, low activity thermogenesis, low sympathetic nervous system activity, and low fat oxidation.

Energy Expenditure In Children

The observation that obesity occurs more frequently in children of obese parents led to a variety of studies to determine how much of the genetic predisposition to obesity is related to energy metabolism. Stunkard et al. reported data on energy intake and energy expenditure in infants born to lean and overweight mothers and concluded that excessive energy intake, rather than low energy expenditure, is the cause of obesity in infants at high risk of obesity (101). Childhood obesity is a vastly unexplored area and more studies are needed to understand how eating behavior forms and solidifies in conjunction with the final maturation of the human brain from childhood to adulthood. A hallmark study (102) found that infants who were overweight at 12 mo of age had a 20 lower TDEE (measured by DLW) compared with normal-weight infants when measured 9 mo earlier (i.e., 3 mo of age). Similarly, low energy expenditure in 5-yr-old girls was negatively correlated with BMI at adolescence (103). In...

Molecular Mechanisms Of Energy Expenditure Variability

The study of obesity in human individuals is inherently difficult. This is because of factors related to the disease itself, including heterogeneity, age-dependent penetrance, uncontrollable gene-environment interactions, and gene-gene interactions. Ultimately, proof that a putative mechanism of energy expenditure actually has a role in maintaining caloric homeostasis must come through genetic studies in animal models and then through the discovery of genetic variability for these mechanisms in humans. It is likely that further gene discoveries in animal models will add to this knowledge and continue to identify novel pathways that are important in nutrient partitioning and energy balance in humans. Evidence that these mechanisms actually promote or limit the development of obesity by stimulating or decreasing energy expenditure or nutrient partitioning must be demonstrated. Some of the significant advances in our understanding of the regulation of energy balance have stemmed from...

Diacylglycerol Transferase

Triglyceride synthesis has been implicated to occur through the acyl CoA diacylglycerol transferases (DGATs), enzymes that catalyze the final reaction in the glycerol phosphate pathway. DGAT enzymes are highly expressed in tissues associated with triglyceride synthesis. In humans, an abundant expression of DGAT enzymes has been observed in adipose tissue and liver (142,143). Dgat1- - mice are leaner than wildtype mice and have smaller adipocytes (120,144). When fed a high-fat diet, Dgat1- -mice are resistant to obesity and are protected from diet-induced hepatic steatosis (120). These effects are likely caused in part by increased energy expenditure. Moreover, Dgat- - mice demonstrate an increase in spontaneous physical activity (145), increased expression of UCP-1 (144,146), and increased leptin sensitivity (144). An intact leptin pathway appears to be required for the effects of DGAT deficiency on energy metabolism. Although DGAT1 deficiency reverses obesity and insulin resistance...

The Characteristic Clinical Course of Retrogenic Dementias

Subsequent studies have supported these observations 103 , Azzarelli et a have studied this phenomenon in detail in neonates 102 , They concluded that, at the moment of insult, damaged brain areas are ones which have the greatest susceptibility to oxygen deprivation. Consequently, at any given developmental age, tissues having higher metabolic rates for glucose should be particularly sensitive to oxygen deprivation. Furthermore, they note that myelinization is related to increased neuronal oxidative activity in oligodendroglia. Hence, brain areas most involved in myelination are the most sensitive to hypoxic damage.

Energy Expenditure and Obesity

Energy expenditure is made up of three components basal metabolic rate (BMR), which can be estimated as resting energy expenditure (REE), which has also been called resting metabolic rate (RMR) thermic effect of food, which makes up only a small fraction of total daily energy expenditure and energy expended in physical activity (EEPA), which is by far the most variable among individuals. Although patients often complain that they have a low metabolic rate, careful studies have conclusively shown that REE is linearly related to lean body mass (72). This means that heavier people have higher REE than thin individuals, and as a result need to eat more on average each day to maintain their higher weight. It is likely that the rise in the prevalence of obesity is the result not only of increased EI associated within the modern food environment, but also of a reduction in the habitual levels of EEPA associated with a modern environment filled with technologies designed to reduce the need...

Electrophysiologic Changes During Ischemia

Significant metabolic changes occur in the ischemic inner wall (subendo-cardium),whereas the metabolic state of the outer wall (epicardium) remains nearly normal. This creates a difference in electrical potential between ischemic and normal tissue with the net result being that there is a current flow from normal cells in the epicardium toward the ischemic cells in the endocardium (Figure 10.1). This current flow takes place during mechanical systole, which, as you know from Chapter 1, occupies the time interval of the ST segment. Because the current is flowing away from ECG electrodes on the body surface overlying the affected ventricular wall, it is registered on the ECG as a negative needle deflection, resulting in ST depression. As you would surmise, these same electrophysiologic events can also alter T waves.

Gases Respiratory Care

The answer is b. (Schwartz, 7 e, p 447.) Shivering is the physiologic effort of the body to generate heat to maintain the core temperature. In healthy persons, shivering increases the metabolic rate by 3-5 times and results in increased oxygen consumption and carbon dioxide production. In critically ill patients these metabolic consequences are almost always counterproductive and should be prevented with other means employed to correct systemic hypothermia. In the presence of vigorous shivering, oxygen debt in the muscles and lactic acidemia develop.

Non Traditional Bioeletrical Signals

The eye has a standing electrical potential across it, as some kind of weak battery, with the front of the globe (cornea) positive and the back negative. This resting or standing potential is generated largely by the transepithelial potential across the retinal pigment. It varies from one to several millivolts (up to 10 in some cases), depending upon the state of retinal illumination, because light leads to a polarization change of the basal pigment membrane. Thus, it is not generated by excitable tissue but, rather, is attributed to the higher metabolic rate of the retina. Interestingly enough, the polarity of this potential difference in the eyes of invertebrates is opposite to that of vertebrates. In fact, this field may be detected with the eye in total darkness and or with the eyes closed. It was first observed by Emil du Bois-Raymond (1818-1896), in 1848, a renowned German physiologist (yes, with a French name). The standing eye potential is not really constant, but slowly...

Proposed Physiological Mechanisms

Meals that are high in GI challenge these regulatory mechanisms, as presented in Fig. 1. To illustrate the dynamic changes that occur following a meal, the postprandial period can be divided into early, middle, and late phases (60). During the early phase (0-2 h after a meal), hyperglycemia can be more than twofold greater following consumption of a high-GI food (e.g., potatoes) compared with a macronutrient-controlled portion of a low-GI food (e.g., legumes) (24,61). Exaggerated hyperglycemia accentuates release of gut hormones and promotes primary hyperinsulinemia, along with hypoglucagonemia. This hormonal milieu enhances the normal anabolic response to feeding described above. The middle postprandial phase (2-4 h after a meal) is marked by a decline in nutrient absorption from the gastrointestinal tract. However, persistent elevation of circulating insulin relative to glucagon stimulates continued glucose uptake by insulin-sensitive tissues, often causing a rapid drop in blood...

Body Weight Regulation

Data from animal research provide support for the proposed mechanism relating GI to nutrient partitioning and energy metabolism. In two experiments by Kabir et al. (74,75), rats were fed diets varying only in carbohydrate source (i.e, high-GI vs low-GI starch) for 3 wk. Based on 14C-glucose tracer studies, insulin-stimulated glucose oxidation was lower, whereas incorporation of glucose into lipid was higher, in rats fed the high-GI diet (74). Furthermore, the high-GI diet provoked changes in insulin-regulated lipogenic and gluconeogenic enzymes as demonstrated by higher fatty acid synthase activity in adipose tissue and lower mRNA for phosphoenolpyruvate carboxykinase in liver (75), respectively. In a study of body composition and energy metabolism, Pawlak et al. (76) fed rats identical diets that, like those in the previously cited studies, varied only in the GI of the carbohydrate source. The rats on the high-GI diet seemed to become more energy-efficient, as indicated by a...

Pharmacological Treatment

These advantages may only apply in mild to moderate depression, as doubts have been expressed about their efficacy in severe and melancholic depression 162-165 . In addition, the elderly may not tolerate SSRIs as well as younger people, being more prone to extrapyramidal symptoms and weight loss 166 . The choice of the SSRI may depend on the propensity of an individual agent to cause adverse effects, especially due to pharmacokinetic drug interactions caused by an inhibitory effect on the hepatic cytochrome P450 metabolic system. In this regard, sertraline and citalopram have the least inhibitory effect and may be the SSRIs of choice 167 .

Calories or Carbohydrates

The focus of the low-carbohydrate approach is on carbohydrate rather than the number of calories consumed. Given that individuals following this approach track the grams of carbohydrate from only a limited number of foods, it is appealing to many dieters because it reduces the burden of accounting for all foods consumed however, it may also reduce awareness of total calories consumed because the emphasis is placed on altering one's metabolic state rather than altering one's energy balance.

Steroid Contraception

These include fluid retention from decreased sodium excretion accelerated development of cholelithiasis increase in hepatic protein production (e.g., coagulation factors, carrier proteins, angiotensinogen) healthy lipid profile changes (increase in high-density lipoproteins HDL decrease in low-density lipoproteins LDL ) and increased venous and arterial thrombosis. Progestin-Mediated Metabolic Effects. These include mood changes and depression from decreased serotonin levels androgenic effects (e.g., weight gain, acne) and unhealthy lipid profile changes (decreased HDL, increased LDL).

The Importance of an Early Diagnosis in Alzheimers Disease

Longitudinal studies of a family carrying the Swedish APP 670 671 mutation also showed reduced glucose metabolism in the temporal lobe prior to impairment of neuropsychological tests and volume changes of the temporal lobes 3 . A reduced hippocampal volume has been reported in subjects at risk of autosomal dominant familiar AD 7 . Neocortical abnormalities in glucose metabolism have been reported to precede neuropsycho-logical impairments in attention, abstract reasoning, visual-spatial function 8 . Left and right cerebral metabolic rate of glucose, expressed as metabolic ratios, gave an 85 diagnostic accuracy, which was improved to 91 when combined with quantitative electroencephalogram 9 . The present limitation of routine single photon emission tomography (SPECT) is that the methods do not provide quantitative measures and the resolution is not as high as PET. Improvement of suitable clinical methods will certainly make functional imaging an important and useful...

Metabolic Basis For Enhancement Of Transdermal Drug Delivery

The concept of a biochemical approach for enhancing cutaneous permeability derives from the dynamic nature of the response to acute barrier disruption. The repair response, regardless of the manner of primary disruption, occurs quickly (over hours). A number of cellular and metabolic responses are required (see above), and if one or more are frustrated, the repair process is delayed (Tables 1 and 2) thus the enhanced window of opportunity for transdermal drug delivery. Through the use of pharmacological agents aimed at inhibiting epidermal lipid synthesis, LB secretion, ECP, or alteration of lamellar membrane composition, the repair response can be modulated. Regardless of the biochemical target, all of these methods alter lamellar bilayer structure by modifying the critical molar 1. Regardless of effectiveness of enhancer, metabolic response to barrier perturbations will result in rapid normalization of barrier function. 2. Strategies that interfere with metabolic response may...

Get at Least an Hour Each Day of Physical Activity

However, it is not clear why this is the case. Physical activity could be important simply because of its effects on energy balance. The more physical activity a person does, the more calories that can be consumed without weight gain. As energy requirements decrease with weight loss, a person who loses weight and does not increase physical activity may have to eat far less than before weight loss. Because food restriction is difficult for most people, increased physical activity may serve to allow the person to consume an amount of food that is sustainable. Alternatively, physical activity may have other metabolic effects that go beyond simply expending more energy. Some have suggested that there is a threshold of energy expenditure below which it is harder to match energy intake to energy expenditure (40). Perhaps the high levels of physical activity seen in NWCR participants help get them above this threshold and makes matching energy intake and expenditure easier. Finally, high...

Drugs on the Near and Distant Horizons

Leptin has been found to ameliorate many of the symptoms of lipodystrophy (86). Nine female patients with lipodystrophy and a serum leptin level of less than 4 mg mL were treated with recombinant methionyl human leptin for 4 mo. Eight of the women had diabetes. During treatment with leptin, the glycosylated hemoglobin decreased an average of 1.9 . During the 4 mo of therapy, triglyceride levels decreased by 60 . Liver volume was also reduced by an average of 28 , and resting metabolic rate also decreased significantly with therapy (87). A reduced body weight is associated with decreased 24-h energy expenditure and decreased leptin and thyroid hormone levels. When body weight was reduced by 10 , circulating T3, T4, and leptin concentrations were decreased. All these endocrine changes were reversed by administration of replacement doses of recombinant human methionyl leptin. Total energy expenditure increased in all subjects during treatment with leptin, indicating that decreased leptin...

Protein Differences Between Omnivores And Vegetarians Or Vegans

Increased thyroid activity is evident from the higher resting metabolic rate of vegans32 and of the elevated thyrotropin levels in vegans.33 This serves to explain why vegans are, on the average, leaner with lower body mass indexes (BMI).32 Also, the immune status in vegans is elevated compared with omnivore subjects in terms of significantly elevated cytokine 2 and gamma interferon levels.34

Defolliculation by Collagenase Treatment

Collagenase treatment adversely affects the metabolic rate of oocytes. The most noticeable is the marked depression in endogenous protein synthesis (4). A common remedy for this is to include a recovery period, usually overnight incubation, before oocytes are used for further experiments. However, such oocytes remain less robust than manually defolliculated oocytes. For example, although it is not uncommon to observe a germinal vesicle breakdown (GVBD) response within 2 to 3 h of the addition of progesterone to manually defolliculated oocytes, it typically takes twice as long to observe it for collagenase-treated oocytes. Also, it is our experience that collagenase-treated oocytes do not always respond to insulin to undergo GVBD. On the other hand, manually defolliculated oocytes almost always respond to insulin (1 M) to undergo GVBD.

Yeast recycling and immobilization

Most winemaking involves separate lots of grape juice fermented to dryness. This is known as batch fermentation. In contrast, most industrial fermentations are continuous fermentations, where nutrients are added at a relatively constant rate once the desired metabolic state of the colony has been reached. The ferment volume remains stable by removing liquid at the same rate that nutrient solution is added. Such fermentations can remain operational for weeks or months. Unfortunately, the technique is ill-suited to wine production, where quality often depends on compounds produced throughout the various stages of colony growth and decline. Because of the cost efficiencies of continuous fermentation, though, several techniques are under investigation to reduce the costs associated with inoculating each separate batch of must with yeast.

Functional Relationship of Glucagon and Insulin

Postprandial Blood Sugar

Insulin, associated with well-fed, absorptive metabolism, and glucagon, associated with fasting and post absorptive metabolism, usually oppose each other with respect to pathways of energy metabolism. Glucagon works through the cAMP system to activate protein kinase A favoring phosphorylation of rate-limiting enzymes, whereas insulin often activates protein phosphatases that dephosphorylate many of the same enzymes. An example of this opposition in glycogen metabolism is shown in Figure 1-9-5. Glucagon promotes phosphorylation of both rate-limiting enzymes (glycogen phosphorylase for glycogenosis and glycogen synthase for glycogen synthesis). The result is twofold in that synthesis slows and degradation increases, but both effects contribute to the same physiologic outcome, release of glucose from the liver during hypoglycemia. Insulin reverses this pattern, promoting glucose storage after a meal.

Physiological Activities

A puzzling observation made a decade ago was that glitazones, which were developed for the treatment of insulin resistance, are PPARg-selective ligands. The link between the promotion of adipocyte differentiation and lipid storage by PPARg and the antidiabetic effects of these compounds is not fully understood. One hypothesis is fat redistribution from muscle to adipose tissue more particularly to subcutaneous fat, which is itself more sensitive to insulin than visceral fat (Gurnell et al., 2003 Wajchenberg, 2000). Alternately, some data support the hypothesis that adiponectin, an adipokine with insulin-sensitizing property and a PPARg target gene, might be a crucial component connecting PPARg activation in the adipose tissue and the metabolic response of the peripheral organs (Gurnell et al., 2003). Other possibilities are the inhibition of hepatic neoglucogenesis or induction of a futile cycle, as mentioned above. Unexpectedly, PPARy+' heterozygous mice, rather than being prone to...

Acetyl CoA Carboxylase

To date more than 600 genetic markers and chromosomal regions have been associated or linked with human obesity phenotypes (154). These have been identified from human obesity cases owing to single-gene mutations, Mendelian disorders, transgenic and knockout models relevant to obesity, quantitative trait loci from animal crossbreeding, association studies with candidate genes, and linkages from genome scans. Future studies will no doubt report that additional genetic loci will prove to affect energy metabolism.

The Normal Physiology Of Sleep

The central nervous system is composed of the entire brain plus the spinal cord. During NREMS, many neurons in the central nervous system have a lower rate of activity than they do during waking, and the overall metabolic rate in the brain is lower than during waking. It is as if the brain is just active enough to keep things going at a basic, low level. It is almost as if it is idling (but as we shall see in Chapters 6 and 12, there is still a lot of mental processing going on). Yet, there are a few areas that are more active than they are during waking. These are the areas that assume control in order to actively produce NREMS.

Luis H Toledo Pereyra

Surgeon-investigators, through history, have introduced innumerable important advances to medicine. Their discoveries enriched cardiac surgery, transplantation, vascular surgery, total parenteral nutrition, metabolic response to trauma, hormonal control of cancer, angiogenesis and genetics, to mention several of them. Clyde Baker, dedicated surgeon-investigator scientist has recently summarized important developments in the history and philosophy of surgical research.3 He emphasized the obstacles the surgeon-investigator must overcome before reaching a stable career, namely, time, economics and discrimination, as well as the inherent factors associated with the surgical persona. Surgeon-discoverers have in common the innovative spirit reinforced by time commitment and an urgent need for accomplishment.

The Complete Disproof Of The Membrane Pump Theory And Its Ancillary Postulations

In 1952 I first presented results of my earlier study on the (would-be) energy requirement of the hypothetical sodium pump in metabolically inhibited frog muscle. To halt respiration, I used pure nitrogen (in addition to sodium cyanide). To halt glycolysis, the alternative route of energy metabolism, I used sodium iodoacetate.

Overview Of The Nuclear Receptor Superfamily

The receptors of the intermediary class are metabolic sensors. This group comprises receptors binding to a broad range of molecules with, as a corollary, a relatively poor affinity. Rather than responding to hormones secreted by endocrine glands with tight feedback controls, these receptors can bind to molecules that are components of metabolic pathways as substrates, intermediates, or end-products. In this class are the PPARs, which are involved in many aspects of lipid metabolism, and more generally in energy metabolism. They can bind a wide variety of fatty acids, from dietary lipids to lipids derivatives such as eicosanoids. The liver X receptors (LXRa and LXRb) recognize cholesterol metabolites such as oxysterols. Together with the farnesoid X receptor (FXR), which binds bile acid derivatives, they are closely involved in cholesterol metabolism. The pregnane X receptor (PXR) is activated by many endobiotic and xenobiotic compounds, a property shared with its close relative, the...

Obesity

Obesity has many different metabolic effects, some of which would tend to increase the risk of CHD. In particular, obesity increases serum total cholesterol while reducing HDL cholesterol, raises blood pressure, and induces glucose intolerance.44 Data from prospective studies also indicate that obesity is an important risk factor for CHD.45,46

Bacteria

Young bacterial cells of the same species are smaller than old bacterial cells of the same species and have a higher growth rate. Young bacterial cells increase in size only to reproduce. The higher growth rate of young bacterial cells as compared to old bacterial cells is due to the larger surface-to-volume ratio of young bacterial cells. The larger surface-to-volume ratio provides more surface area for the absorption of substrates and nutrients and, consequently, a higher metabolic rate of activity including growth and reproduction.

Hormone Tests

Healthy endocrine glands provide a constant source of hormones that are only secreted when needed to maintain homeostasis, a stable internal environment. Metabolic rate, blood pressure, metabolism of all nutrients, primary and secondary sex characteristics, and regulation of serum electrolytes are all affected by increases and decreases in hormone levels.

Metabolome analyses

Analogous to the proteome, metabolome can be defined as the metabolite complement (the low molecular weight intermediates of metabolism) of a cell, in a particular physiological state (Oliver et al., 1998 Tweeddale et al., 1998). Quite like the proteome and unlike the genome, its composition is relative to the physiological state of the cell, with the potential to be more dynamic between different states. Metabolites are the currencies of the cell mediating cellular activities. Defining the metabolome, or even a metabolite, is not as easy as it appears. A metabolite can be classified based on its origin as 'endogenous' (i.e. arising from within the cell) or 'exogenous' (i.e. arriving from outside the cell), and based on its function as primary (central to the metabolic needs of the cell) or secondary (of less importance to the cellular machinery). The boundaries between these classifications are not entirely clear-cut and are subject to interpretation. Xenobiotics and the...

Diuretics

The selection of a diuretic is based on the severity of the HF and whether the HF is related to systolic or diastolic dysfunction. Mild HF often responds to thiazides, such as hydrochlo-rothiazide (Esidrix, HydroDIURIL, Oretic, etc.), which require adequate renal function (creati-nine clearance > 30 mL per minute). Peripheral edema in mild HF also responds to the nonthi-azide diuretic indapamide (Lozol), which has fewer adverse electrolyte and metabolic effects than hydrochlorothiazide and can be used in patients with moderate renal failure (creatinine

Aspirin Salicylates

Salicylates are the most common cause of drug poisoning in the United States. Salicylates uncouple oxidative phosphorylation and increase the metabolic rate, resulting in tachypnea, tachycardia, fever, and hypoglycemia. The Krebs cycle is also inhibited, causing a metabolic acidosis. In addition, damage to hepatocytes occurs, causing liver toxicity, prolonged prothrombin time, platelet inhibition, and prolonged bleeding time.

Indirect Calorimetry

Open-circuit spirometry provides a relatively simple way to measure oxygen consumption at rest and during exercise. The individual inhales ambient air with a constant composition. Changes in oxygen and carbon dioxide percentages in the expired air compared with percentages in inspired ambient air reflect ongoing energy metabolism. With the addition of the volume of air breathed during a specific time period, respiratory gas exchange can be measured and energy expenditure calculated indirectly. Early measurements of resting metabolic rate were performed using mouthpieces or face masks, but these have now been replaced by ventilated hood systems to improve the comfort for the individual. During the past three decades, the indirect calorimetry method has been applied to confined rooms called respiratory or metabolic chambers (4-16). These chambers are large enough (12,000-40,000 L) for an individual to live in comfortably for several days. Respiratory chambers enable the measurement of...

Adrenergic Receptors

P3-adrenergic receptors ( 3-ARs), which are located in skeletal muscle (88) and both white (110) and brown (111) adipocytes, have been demonstrated to significantly regulate antiobesity and insulinsensitizing actions in rodents (see, e.g., refs. 112,113). Mice lacking 3-ARs have a modest increase in body fat, indicating that 3-ARs play a role in regulating energy balance. Acute treatment of normal animals with 3-selective agonists leads to increased serum FFA and insulin levels, increased whole-body energy expenditure, and decreased food intake, whereas when administered to 3-AR- - mice, each of these effects was completely absent, indicating that these responses are mediated exclusively by 3-ARs (114). Indeed, testing in humans of the first generation of 3-AR agonists, such as BRL 26830A (115,116) and CL 316243 (117), revealed encouraging antidiabetic and antiobesity characteristics including energy metabolism. However, some of these compounds shared substantial selectivity with the...

Leptin

In 1994, the genetic mutation causing massive obesity in ob ob mice was described (123). The gene encodes an adipocyte-derived hormone known as leptin, which acts primarily on the hypothalamus as a lipostat, thus tending to adjust the size of the body's energy stores. Mice homozygous for the ob mutation completely lack the presence of circulating leptin these animals develop severe, early-onset obesity, with many associated metabolic and hormonal abnormalities including hyperphagia, defective ther-mogenesis, infertility, and type 2 diabetes. The next experiments demonstrated that these metabolic and physiologic abnormalities were rapidly corrected by leptin administration, which caused significant reductions in food intake and increased energy expenditure resulting in weight loss after only a few days of leptin administration (124-126). These findings led to optimism that leptin therapy might be important for treating human obesity. The human gene encoding leptin has been screened in...

Cardiac arrhythmias

Increased ventricular ectopic activity has been documented after ingestion of substantial amounts of alcohol, although epidemiological studies have not shown a higher risk of sudden death in drinkers (Siscovick et al. 1986). Speculation about the mechanisms for the relation between heavier drinking and arrhythmias include myocardial damage, electrolyte disturbances or other metabolic effects, vagal reflexes, effects upon nerve or muscle cell conduction refractory times, catecholamines, and acetaldehyde. A Finnish report (Maki et al. 1998) involved study of men with recurrent alcohol-associated atrial fibrillation. In controlled analyses of a number of tests and measurements, there was some evidence for exaggerated sympathetic nervous system reaction in these people.

The Thyroid Gland

When thyroxin reaches the cells of the body, it stimulates them to use more oxygen. This increases the metabolic rate, or basal metabolism, of the body. Basal metabolism is defined as the amount of oxygen the body uses per unit of weight when the body is at rest. Thyroxin also functions to regulate the growth of organs aid in mental development aid in sexual development and aid in the metabolism of water, electrolytes, proteins, glucose, and lipids. The Basal Metabolic Rate test may be used to measure the effect of thyroxin on the body.

The Adrenal Glands

Glucocorticoids have several different metabolic effects. They cause deposition of glycogen in the liver, gluconeogenesis (conversion of amino acids to glucose), liberation of amino acids from proteins, mobilization of fats, decreased utilization of glucose, and an increase in blood glucose levels. Hydrocortisone is the principal example of a glucocorticoid. Hydrocortisone and cortisone both have sodium-retention effects. Both hydrocortisone and cortisone have anti-inflammatory actions and cause dissolution of lymphoid tissue. Synthetic steriods have more effect on inflammation than do naturally occurring steroids.

Heat Production

Most of the heat produced by the body comes from oxidation of the food we eat. Metabolic rate is the term for the rate at which the heat is produced. The rate at which heat is produced depends on the following (5) Certain hormones. Certain hormones may increase a person's metabolic rate, thus increasing that person's heat production.

Exercise

Because exercise expends calories, it is a logical part of any weight-loss program. Overweight persons are generally inactive, spending much of their day sitting or lying down (84,85). Many of them, particularly the heavier ones, have a real problem walking even short distances and climbing steps and tend to avoid situations that require such activities. By remaining as sedentary as they do, they are essentially almost at their resting metabolic rate for most of the day. These persons must be taught first to walk, then to walk faster, and then to run or bicycle or do aerobic dance. An exercise program must start slowly. If an obese person is pushed too rapidly, discomfort and avoidance occur. Careful observation for and treatment of skin intertrigo, dependent edema, and foot or joint injuries is mandatory. It is helpful to educate the patient about how many calories are spent in an individual exercise activity. Most tables of caloric expenditure with given levels of activity have been...

Weight Maintenance

Maintaining reduced weight once a loss has been achieved is very difficult. There is a persistent tendency to regain the weight , and there is experimental evidence that the metabolic rate is abnormally depressed after weight loss (92) and that lipogenic pathways enhancing the reaccretion of fat may be particularly efficient. Although the diet may be liberalized after the goal weight has been reached, it must be done gradually, with daily weight monitoring. A limitation of caloric intake will be required indefinitely (93). All the lifestyle changes learned during the weight-loss period need to be continued, including the exercise program. More long-term experience with the efficacy and safety of drugs for longer than 2 yr of use is necessary. Perri et al. (70,94,95) have reported the positive influence of frequent contact on weight maintenance.

Novel Therapeutics

Other novel substances are on the horizon which, when administered parenterally, have insulin-sparing or insulin-like effects. Leptin, also known as the obesity gene product, has been linked to lower glucose levels, improved insulin sensitivity, regulation of adipose stores, myocardial antihypertrophic effects, and enhanced P-cell function. Leptin can delay the onset of type 2 diabetes, inhibiting fat formation and speeding its depletion. Deficiency of leptin or leptin insensitivity has caused obesity and altered metabolic rates in humans and animals.

Cardiovascular Role

When stress, environment, or some other factor causes the body's temperature to be above normal, impulses stimulate the heat- losing center. Heat reducing mechanisms are set in motion. Blood vessels in the skin dilate (get bigger). More warm blood moves to the skin. The skin becomes warm, and the excess heat radiates out to the environment. The slower metabolic rate helps bring the temperature of the body down to normal.

Hyperthyroidism

Because the Irish physician, Robert Graves, first described hyper-thyroidism around 1835, this condition is usually referred to as Graves disease. Hyperthyroidism is increased secretion of thyroxine. Graves disease is characterized by anxious behavior, rapid pulse rate, increased appetite, weight loss, elevated metabolic rate, tremor of the hands, and exophthalmos (a condition in which the eyeballs slightly protrude from the sockets giving the patient a startled appearance). Graves's disease can be treated by the administration of Iodine 131 (I131) or by surgery. Surgery is the first choice of treatment in patients whose age is between 25 and 40 and the second choice of treatment in patients 0 to 25 years.

Early Diagnosis

Human aging is joined by various physical, social and cognitive-mnestic changes, which can considerably differ inter- and intra-individually. Cog-nitive-mnestic changes are caused by processes in the central nervous system, but they are also determined by genetic factors, education, profession, life style, intellectual and physical activity, and especially general physical condition. Reliable norms about cognitive and mnestic functions in elder people are usually lacking. Many tests just indicate norms for a group elder than 60 years. In gerontopsychological literature, sometimes an allocation in young olds'' (65-75 years), old olds'' (75-85 years) and eldest olds'' (> 85 years) is made, in order to take into account the heterogeneity of elder people. Furthermore, there are often problems in the design of neuropsychological studies. In the cross-sectional approach, age-dependent impairments are often overestimated, while in longitudinal studies they are underestimated. Since the...

Combination Therapy

Thiazide diuretics have been most often associated with aggravating glycemic control because, by induction of hypokalemia, they may inhibit insulin output from the pancreas. Indapamide (Lozol), in low doses, reduces blood pressure without worsening glycemic control or lipid profile. Long-term trials with indapamide did not show an increased incidence of diabetes compared with other diuretic agents. Additionally, low-dose thiazide therapy is generally not associated with adverse metabolic effects.

Glucose Transporter

Transgenic mouse models have been developed to directly assess how modulation of the glucose transporter may affect in vivo glucose disposal and energy metabolism. Disruption of GLUT4 gene has resulted in severely reduced adipose tissue deposits and growth retardation. Mice deficient in GLUT4 have increased blood glucose levels in the fed state, and are less sensitive to insulin action, indicating possible insulin resistance. GLUT4-null mice demonstrate that functional GLUT4 protein is not required for maintaining normal blood glucose levels, while GLUT4 is absolutely essential for sustained growth and normal cellular glucose and fat metabolism (177).

Stag watching

Table 6.3 Emergence times for arboreal marsupials in the Central Highlands of Victoria. The information is a synthesis of data presented by Lindenmayer et al. (1991 b, 1991e). A dash (-) indicates that insufficient data were available to calculate values. Values for field metabolic rates are from Nagy (1987) and are based on data for adult animals. Approximate values to the nearest 5m are given for nest entrance height and to the nearest 5 minutes for emergence time. Table 6.3 Emergence times for arboreal marsupials in the Central Highlands of Victoria. The information is a synthesis of data presented by Lindenmayer et al. (1991 b, 1991e). A dash (-) indicates that insufficient data were available to calculate values. Values for field metabolic rates are from Nagy (1987) and are based on data for adult animals. Approximate values to the nearest 5m are given for nest entrance height and to the nearest 5 minutes for emergence time. Metabolic rate (kj d)

Adiponectin

Interestingly, adiponectin proteins can bind to each other in varying numbers, and the resulting combinations appear to have differing levels of importance in terms of their effects on metabolic homeostasis. In particular, adiponectin circulates as low-molecular-weight (LMW) and high-molecular-weight (HMW) forms (27). The HMW form has been shown to be the most metabolically active, with its primary effects thought to be on the liver (28). Initially, a fragment of the adiponectin molecule lacking the N-termi-nus, referred to as the globular domain, was thought to have significant metabolic effects, as suggested by animal studies (29). However, its presence has not yet been confirmed and it most likely does not normally circulate in humans, leaving the physiological significance unclear (30). Very recently, a new family of highly conserved proteins, homologous to adiponectin, has been identified (64). In vitro models suggest that some of these adiponectin paralogs may have metabolic...

Uncoupling Protein

UCP-3 is abundantly expressed in skeletal muscle, an important tissue for thermogen-esis (53). Phenotypes of mice in which UCP-3 genes have been inactivated do not indicate that these homologs have a function in regulating either body temperature or body weight (134-137). In one study in which UCP-3 was overexpressed in skeletal muscle of transgenic mice, mice showed a resistance to diet-induced obesity and an improvement in insulin sensitivity (138). As the amount of UCP-3 in the muscle of the transgenic mice was at a level that had been shown previously, by the same group of investigators, to be toxic to the mitochondria of mammalian cells, it is possible that the mitochondria of the transgenic mice were leaky owing to toxicity from the high levels of UCP-3 (139). Consequently, the effects of the UCP-3 transgene expression were not indicative of normal physiological function. A recent study, in which UCP-3 was induced in human muscle by a high-fat diet and then the rate of recovery...

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