Costs Associated With Obesity

In addition to the impact of obesity on mortality and comorbid health, there are now a great deal of data demonstrating that obesity is responsible for increased medical costs, job absenteeism, and a reduced quality of life for both adults and adolescents (7,8). Obese individuals have more visits to primary care providers and are the recipients of more diagnostic and specialty services (9). In a study of more than 16,000 Medicare recipients, Daviglus et al. found that individuals who were...

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...

Genetics

Though accounting for a relatively small portion of obesity in the pediatric age group, a number of endocrine disorders and genetic syndromes can be causally linked to childhood obesity. Of note is that these disorders are generally accompanied by poor linear growth and developmental delay. Recent studies of large family pedigrees have also identified a number of genetic loci that appear to be associated with severe obesity (103). One such genetic locus found in some obese individuals is that...

Defining Obesity Body Mass Index

There is general agreement that BMI, which is the weight adjusted for height, is the best way to initially evaluate patients for obesity. BMI, generally expressed as kg m2, is easily determined using measured height and weight and a table such as the one provided in the NHLBI and North American Association for the Study of Obesity's (NAASO, the Obesity Society) Practical Guide on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (Table 1) (35). An individual...

Control Of Energy Intake

Food intake in mammals, including humans, occurs in distinct bouts or meals, and the number and size of meals over the course of a day comprises the meal pattern. Food intake is thought to be regulated by signals from the gut, brainstem, and hypothalamus. Most humans are quite habitual in that they eat approximately the same number of meals, and at the same time of day (24,25). Factors or signals that control when meals occur are different from those that control when they end i.e., different...

Energy Homeostasis and the Endocannabinoid System

In this chapter we review the endocannabinoid system. It represents a novelly described and quite different kind of intercellular signaling system within the body, and we focus on how it influences energy homeostasis as well as how it might be exploited to treat obesity and its complications. Although synthetic and plant-derived cannabinoids such as A9-tetrahydrocannabinol (A9-THC) have long been recognized to influence food intake, it is only relatively recently that endogenous cannabinoids...

Lots of Physical Activity

NWCR participants report engaging in very high levels of physical activity to maintain their weight loss. From self-reports we have estimated the average energy expenditure from physical activity to be about 2800 kcal wk (3). This would correspond to about 1 h each day of moderate-intensity physical activity. Walking was the most frequently reported form of physical activity. We asked a subsample of NWCR participants to wear pedometers. We found that the average number of steps per day was...

Short Term Weight Loss

It has been clearly established that effective behavioral weight-loss interventions result in approximately a 10 weight loss compared to initial body weight within 6 mo of initiating an intervention (12). These results appear to be achievable with the combination of a reduction in energy intake and an increase in energy expenditure (1). However, the contributions of each of these components (reduction in energy intake and increase in energy expenditure) are not equal, with the majority of...

The Dualcenters Hypothesis

Historically, the conceptual framework that dominated thinking about the role played by the hypothalamus in the control of food intake was the dual-centers hypothesis proposed by Stellar in 1954 (1). In the same year that the discovery of leptin refocused attention on the role of the hypothalamus in energy balance, Psychological Review honored this article as one of the 10 most influential articles it had published in a century of publications. Stellar eloquently argued that the hypothalamus is...

Reductions in Dietary Energy Density as a Weight Management Strategy

Blanck, PhD, Laura Kettel Khan, PhD, Mary K. Serdula, md, Jennifer D. Seymour, PhD, Beth C. Tohill, PhD, and Barbara J. Rolls, PhD Introduction What Is Energy Density Population-Based Studies Experimental Studies Clinical Interventions Practical Strategies to Reduce Energy Density Reducing caloric intake is the cornerstone of dietary therapy for long-term healthy weight management. Strategies individuals have typically used include limiting portion sizes, food...

Plasminogen Activator Inhibitor1

Plasminogen activator inhibitor (PAI)-1 is released by adipocytes, as well as other adipose tissue constituents, with visceral fat contributing higher amounts compared to subcutaneous depots (81). This adipokine acts as an inhibitor of fibrinolysis and proteinolysis (118), thereby helping to maintain vascular homeostasis. Higher levels of this protein promote increased susceptibility to clotting, a critical event in the pathogenesis of such conditions as myocardial infarction and stroke. Its...

Choose Foods Low in Energy Density

Will decrease the energy density of this snack to 0.96 kcal g and lower the calorie content to 130 kcal. The energy density of mixed dishes can also be reduced by adding water-rich ingredients such as fruits and vegetables or by reducing the amount of added fat. For example, the energy density of lasagna can be lowered by increasing the amount of vegetables in the dish (add chopped spinach, shredded carrots, or broccoli) and reducing the fat content (choose lower-fat meat and cheese, or simply...

Low Fat Diets Are Best for Preventing Weight Regain

Most successful weight-loss maintainers eat a low-fat, high-carbohydrate diet that is low in total calories. Even though there is great controversy in the literature over the best diet composition for maintaining a healthy body weight, the overwhelming majority of the NWCR participants report eating a diet with less than 30 fat and that is high in carbohydrate to keep their weight off. It is important to note that we did not see all NWCR participants eating a low-fat, high-carbohydrate diet to...

Persistence Sequelae and Costs of Pediatric Overweight

Increased body fatness can occur at any age and may or may not persist. The longer a child is overweight, the more likely it is that he or she will be overweight as an adult. At any point in time the positive predictive value of early obesity increases with the age of the child but never reaches 100 . One of the most significant risks of childhood obesity is that it is a strong predictor of adult obesity and the medical complications associated with obesity in adult life, such as diabetes,...

Can Physical Activity Prevent Weight Gain

Close examination of prevalence data indicates the need to focus intervention efforts on the prevention of weight gain. If effective, this will decrease the likelihood of a transition from normal weight to overweight or obesity, and decrease the transition from overweight to obesity. There is some evidence that LTPA can play a significant role in the prevention of weight gain this is mostly likely a result of the increase in energy expenditure resulting from an increase in LTPA. For example,...

Anabolic Effector Systems

Neuropeptide Y (NPY) is one of the most potent stimulators of food intake (115-117), and is proposed to be an anabolic effector that induces positive energy balance. NPY is a highly expressed peptide in the mammalian CNS (118,119), and is well conserved across species. Hypothalamic NPY neurons are found primarily in the arcuate (ARC) and dorsomedial nuclei, and in neurons such as the PVN (120-125). Endogenous release of NPY is regulated by energy balance. Specifically, in the ARC, food...

Barry E Levin md

Gestation, Lactation, and Maternal Environment Perinatal Environment and Brain Development Conclusions References Epidemiological studies suggest that maternal undernutrition, obesity, and diabetes during gestation and lactation can all produce obesity in offspring. Animal models provide a means of assessing the independent consequences of altering the pre- versus postnatal environments on a variety of metabolic, physiologic, and neuroendocrine functions that lead to the development of...

Exercise Lifestyle Modification

There is some evidence that lifestyle modification (diet and exercise) may be an effective adjunct to the treatment of PCOS. The use of hypocaloric diets improves the metabolic derangements in those patients, and low-calorie, low-fat diets have been shown to improve clinical parameters and lower insulin and testosterone levels in PCOS patients (169,170). Weight reduction has also been shown to increase noradrenalin sensitivity in PCOS patients, as PCOS patients have a marked reduction in the...

Laboratory Evaluation of the Obese Patient

Although one could make a case for obtaining a large number of biochemical tests in the evaluation of an obese patient, a more limited initial screen seems warranted. A fasting sample of blood for glucose total, LDL, and HDL cholesterol and triglyceride levels is clearly indicated. These tests, along with an appropriate history, will provide the information necessary for cardiovascular risk stratification and can be used to rule out diabetes or impaired fasting glucose (25,57). Some have...

Hirsutism

Hirsutism is defined as excess body hair in undesirable locations and, as such, is a subjective phenomenon that makes both diagnosis and treatment difficult. Most commonly hirsutism associated with PCOS tends to be an androgen-dependent, midline-predominant hair growth. It is important to note that other factors than androgen action may contribute to the development of hirsutism. Hyperinsulinemia that accompanies many benign forms of virilization can also stimulate the pilosebaceous unit...

Exercise Mode

The majority of clinical trials have incorporated aerobic forms of physical activity (i.e., brisk walking) into the weight loss interventions overweight obese individuals report that walking is the self-selected mode of physical activity for 80 to 90 of activity sessions (20). This may be a result of ease of participation for most individuals, the low cost of participation, and lack of need for special skills to participate in this form of physical activity. Despite these findings, additional...

Abnormal Glucose Metabolism and Type 2 Diabetes

Excess weight is the most important modifiable risk factor for the development of type 2 diabetes. The incidence of diabetes rises as obesity prevalence increases (15). The prevalence of reported diabetes is 2.9 times higher in overweight than in nonoverweight persons in the NHANES data (16). Obesity is associated with type 2 diabetes mellitus in both women (17) and men (18). Also, the longer that people are obese, the higher becomes their risk of developing diabetes (19). From 1990 to 1998,...

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...

P Hydroxydehydrogenase1

Cushing's disease or administration of exogenous glucocorticoids such as prednisone are often associated with increased weight gain, central adiposity, increased food intake, insulin resistance, and in certain individuals, increased likelihood of developing diabetes. However, in general, obese individuals do not have increased circulating levels of cortisol. Interestingly, over the past few years, research has demonstrated that certain enzymes can actually convert inactive cortisol metabolites...

Proglucagon Derived Peptides

Preproglucagon is a peptide made both in the periphery and in the CNS. Preproglucagon encodes two peptides with described central activity glucagon-like-peptide 1 (GLP-1) and glucagon-like-peptide 2 (GLP-2). Both peptides are made in the L-cells of the distal intestine and have well-described functions in the periphery, with GLP-1 critical for enhancing nutrient-induced insulin secretion (202) and GLP-2 playing an important role in maintenance of the gut mucosa (203). Preproglucagon is also...

Endocannabinoids And Regulation Of Energy Balance

Early animal studies demonstrated that systemic or oral administration of A9-THC potently increases food intake. Administration of CB1 antagonists, conversely, blocks the orexigenic action of exogenous cannabinoid agonists and also decreases food intake and body weight in laboratory animals (reviewed in ref. 16). Based on these promising observations, considerable research is currently under way to elucidate the mechanisms of action of endocannabinoids and to determine the feasibility of using...

Efficacy Of Lowcarbohydrate Diets On Insulin Sensitivity And Glycemic Control

A limited number of studies have compared the effects of low- and high-carbohydrate diets on insulin sensitivity. Differences in methodology preclude a pooled analysis of measures of glucose and insulin (32) however, there is some evidence to suggest that low-carbohydrate diets are effective in improving insulin sensitivity and glycemic control (10,11,48). Samaha et al. (10) measured fasting glucose and mean glycosylated hemoglobin levels in nondiabetic and diabetic participants and insulin...

Proposed Physiological Mechanisms

Elegant homeostatic regulatory mechanisms exert tight control over blood glucose concentrations during the postprandial period to ensure a smooth transition from the fed to the postabsorptive state. In the normal fed state, nutrients stimulate release of incretins, including glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), into the circulation from endocrine cells located in the gut. The incretins augment the effects of rising blood glucose in stimulating...

Insulin Hypothesis

The discovery of hyperinsulinemia (13) and insulin resistance in women with PCOS (14) led to a de-emphasis on the ovary as a diagnostic criterion, and resulted in the insulin hypothesis. In insulin resistance there is a defect of insulin receptor at the postbinding level, leading to abnormality of postreceptor insulin signaling and glucose transport (15). This leads to overproduction of insulin to compensate for the perceived lack of effect, and over time to P-cell exhaustion and ultimately...

Conclusions

The research and topics presented in this review are by no means the entirety of work into the CNS regulation of food intake and appetite. In fact, there are rich areas of investigation that we have been able to mention only briefly. The important conclusion from all of this work is, however, that the regulation system and specifically the CNS control of this regulation is diverse and yet exquisitely integrated. From signals arising in the gastrointestinal tract, to hormones that convey...

Daniel H Bessesen md

Division of Endocrinology, University of Colorado at Denver and Health Sciences Center, Denver, CO 2007 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. The content and opinions expressed in this book...

Distribution

The concentrations of ECs within the brain vary considerably by area (10,33). 2-AG is around two orders of magnitude more abundant than anandamide in most brain areas, with the highest levels of both occurring in the brainstem, hippocampus, and striatum (34) the two can be synthesized in the same tissues independent of one another (5). Both anandamide and 2-AG are also produced in several peripheral tissues, including skin, gut, liver, adipose tissue, and testis (26,34). Anandamide circulates...

Magnetic Resonance Imaging Quantification of Tissue Size

MRI does not employ ionizing radiation, but rather is based on the interaction between strong magnetic fields and hydrogen nuclei (protons), which are abundant in all biological tissues, and form the basis for generation of fat and muscle images (60,86). As MRI is not associated with any known adverse side effects, it is the method of choice for assessing whole-body tissue composition. However, the image acquisition time for MRI is significantly longer than CT and image analysis is more complex...

Laboratory and Diagnostic Studies

Laboratory and diagnostic studies should be conducted as part of the initial evaluation to assess the patient's risk or presence of comorbidities. Such laboratory studies should include a fasting lipid profile, fasting insulin and glucose, and liver function tests. Should the history and physical examination suggest the presence of pseudotumor, a head CT scan should be ordered and consultation with a pediatric ophthalmologist arranged. Orthopedic complaints should lead to the use of relevant...

Proglucagon Gene Products

Post-translational processing of preproglucagon results in the production of several peptides in the gut, pancreas, and brain (Fig. 2). These include oxyntomodulin (OXM) and GLP-1 and GLP-2 peptides, which are involved in the regulation of food intake. Prohormone convertase enzymes 1 and 2 cleave preproglucagon and produce different products, depending on the tissue. In the pancreas, glicentin-related pancreatic polypeptide (GRPP), glucagon, and GLP-1 and GLP-2 are produced. The latter two are...

PP Fold Family of Peptides

The PP fold family of peptides include peptide YY (PYY) and PP from the gut and NPY from the central nervous system. These peptides are structurally similar. They are all small (36 amino acid) peptides containing several tyrosine residues. They are characterized by a specific tertiary structure known as the PP fold, and they become biologically active following COOH-terminal amidation. The PP fold tertiary structure consists of a characteristic u-shape double helix one a and one polyproline,...

Costs

What about costs A careful cost analysis was done in the DPP (98). The direct medical cost of laboratory tests to identify one subject with impaired glucose tolerance was 39. Over three years, the direct medical costs of the interventions were 9 per participant in the placebo group and 780 in the ILS. The direct medical costs of care outside the DPP were 432 less per participant in the ILS compared with the placebo. Indirect costs were 174 less in the ILS than placebo. From the perspective of a...

Physical Examination

A careful general physical examination is useful in the evaluation of the obese child. Such an examination yields identification of physical findings that may suggest an underlying endocrine syndrome or genetic disorder. The physical examination should include an overall assessment of the child's body habitus and notation of the pattern of fat distribution. Careful measurement of the height and weight of the child is important to rule out underlying short stature, which may indicate an...

Applying MI to Obesity Conceptual and Pragmatic Issues

There are several aspects of obesity counseling that pose unique challenges for the MI counselor. First, for pediatric obesity, depending on the age of the patient, the intervention may occur directly with the parent(s), directly with the child, or both. There is some evidence that older obese children do not benefit from the involvement of their parents, whereas parent involvement may be beneficial for younger children (46). However, it is not known at what ages youth and parents should be...

Anti Obesity Drugs

Apart from diet, combination with pharmacological treatment with metformin or with weight-reducing agents has been used when required for further weight reduction. It has been reported that the combination of a low-calorie diet with metformin treatment induced greater reduction of body weight and visceral obesity in women with PCOS compared with a low-calorie diet and placebo treatment (136). Weight-reducing agents have been shown to increase the effect of lifestyle modification in reducing the...

Clinical Use Of Cb1 Antagonists Sr 141716

The selective CB1 antagonist SR 141716 (rimonabant or Acomplia Sanofi-Synthelabo), when administered to marijuana smokers, caused weight loss in overweight and obese subjects without causing adverse side effects (118). Based on this and the promising studies on animals (reviewed previously), SR 141716 has been used in randomized, double-blind clinical trials to determine its efficacy in treating obesity and related metabolic complications. Several Phase III clinical trials named RIO (Rimonabant...

Bariatric Surgical Procedures

Weight loss surgeries fall into one of two categories restrictive and restrictive-malabsorptive (see Chapter 19 for illustrations of surgeries). Restrictive surgeries limit the amount of food the stomach can hold and slow the rate of gastric emptying. The vertical banded gastroplasty (VBG) is the prototype of this category but is currently performed on a very limited basis owing to a lack of effectiveness in long-term trials. Laparoscopic adjustable silicone gastric banding (LASGB) has replaced...

Hypothalamic Circuitry Central Pathways

In addition to neuroregulation, discussed in the previous chapter, the hypothalamus integrates chemical and humoral signals from the gut, and hormonal signals from the periphery (adipose tissue), for the regulation of appetite and energy homeostasis. It contains several nuclei the lateral nuclei, ventromedial nucleus (VMN), dorsomedial nucleus (DMN), paraventricular nucleus (PVN), perifornical, and arcuate nuclei and anatomically, it is in close proximity to the brain stem, amygdala, and higher...

Melanocortins

The action of leptin, and possibly insulin, on feeding behavior is transduced by the melanocortin signaling pathway in the hypothalamus (227). The arcuate nuclei in the hypothalamus contain two distinct populations of neurons that highly express the leptin receptor. These neurons are the POMC and agouti-related protein (AgRP) NPY neurons, which project onto neurons in the paraventricular and lateral hypothalamic area known to express the melanocortin receptors. The POMC-containing neurons...

Algorithm For Using Currently Available Drugs

Guidance on the use of medications to treat obesity can be found in a variety of sources (7-9). One algorithm recently proposed is by the American College of Physicians (9). It provides an organized approach and a framework to comment on drugs for the treatment of obesity. As a document prepared by physicians, it emphasizes the medical model in which drugs are used to treat symptoms. However, the algorithm shown in Fig. 1, from a National Heart, Lung, and Blood Institute (NHLBI) report, is a...

Adipose Tissue

White adipocytes express CB1 receptors (16,17,20), and in vitro experiments demonstrate that the CB1 agonist WIN-55,212 stimulates adipocyte differentiation and increases the activity of lipoprotein lipase both actions are blocked by pretreatment with SR 141716 (16). These findings imply that EC activity in white fat has the potential to facilitate growth of new fat cells as well as an enhanced ability to remove fat from circulating lipoproteins and deposit it into fat cells. Furthermore, as...

Inflammatory Alterations In Adipose Tissue With Obesity

The profile of adipokines synthesized and secreted in adipose tissue changes dramatically as individuals become obese. one of the first clues that adiposity alters adipose tissue function was that adiposity was associated with increased expression of inflammatory cytokines, in particular TNF-a and interleukin (IL)-6 (65). TNF-a is a member of a family of secreted proteins that are characteristically produced by immune cells. Cytokines can exert their effect locally via paracrine autocrine...

Contributors

Vian Amber, MBChB, MSc, PhD, MRCPath Department of Metabolic Medicine, Imperial College London, Hammersmith Campus, London, UK Yuhua Bao, PhD RAND Corporation, Santa Monica, CA Stephen C. Benoit, PhD Department of Psychiatry, Obesity Research Center, University of Cincinnati, Cincinnati, OH Daniel H. Bessesen, md Division of Endocrinology, University of Colorado at Denver and Health Sciences Center, Denver, CO George L. Blackburn, md, PhD Division of Nutrition, Center for the Study of Nutrition...

Syndecan3

Syndecan-3, a neuronal heparan sulfate proteoglycan (HSPG), was recently identified as a modulator of feeding behavior by acting as a coreceptor for the melanocortin receptors in the hypothalamus (240). Syndecan-3 expression is regulated by nutritional status ablation of the gene leads to reduced food intake and resistance to high-fat diet-induced obesity (241). The finding was quite unexpected, but provides a novel mechanism for regulating body weight. Syndecan-3 is a member of a family of...

Conclusion

Although historically adipocytes have been thought of basically as a reservoir of triglyceride, it is clear that AT can synthesize and secrete local as well as systemic mediators of metabolism. Thus, AT can be viewed as an endocrine organ. In lean individuals small adipocytes secrete adipokines, such as leptin and adiponectin, which promote healthy metabolic homeostasis. However, with the onset of obesity, a macrophage-mediated profile is observed in AT. Multiple cytokines, such as TNF-a and...

Tumor Necrosis Factora

Of recent intense study, TNF-a has been at the center of attention as a mediator of obesity. Earlier observations in the literature revealed that adipose tissue expression of TNF-a was positively correlated with insulin resistance in humans (67-69) and that as humans became obese, adipose tissue expression of TNF-a increased (67). It is now known that the vast majority, approx 95 , of TNF-a in adipose tissue of obese individuals is synthesized by macrophages, with only a small percentage...

Biliopancreatic Diversion

BPD is a malabsorptive procedure in which a distal gastrectomy and Roux-en-Y configuration are created with a short common limb. The duodenal switch (DS) procedure is similar to BPD, but a duodenojejunostomy is performed to limit marginal ulceration (Fig. 2). BPD is effective in inducing weight loss, particularly in super-obese patients (BMI > 50) (37), but can cause significant complications (38). It involves gastric resection and diversion of the biliopancreatic juices to the terminal ileum...

MI Studies Addressing Dyslipidemia and Diabetes Dietary Intervention Study in Children

The Dietary Intervention Study in Children (DISC) was a multicenter, randomized controlled trial sponsored by the National Heart, Lung, and Blood Institute to assess the efficacy of dietary counseling to decrease elevated serum lipids (LDL-C). Children with elevated LDL-C entered the initial clinical trial when they were 8 to 10 yr of age (34). As the intervention cohort moved into adolescence, the investigators elected to add an MI-based intervention to renew adherence to the prescribed diet...

Protein Sparing Modified Fast

Sometimes referred to as very-low-calorie diets (VLCD) or liquid diets, the protein-sparing modified fast (PSMF) is used on an inpatient or outpatient basis only for adolescents and adults suffering from very severe obesity. Studies published in the 1980s suggested that inpatient modified fasting could be used safely in treating severely obese patients (89) as long as careful monitoring of electrolytes and cardiac status was included in the treatment protocol. Little has appeared in the...

Peripheral Signals

Insulin from the pancreas, leptin from adipose tissue, and gut peptides (PYY3-36, GLP-1, CCK, and OXM) from the gastrointestinal tract (GIT) are known anorexigenic hormones peptides. They directly inhibit NPY AgRP and stimulate POMC CART in the arcuate nucleus (11). Reciprocal to this is the orexigenic gut peptide ghrelin. Ghrelin stimulates NPY AgRP and inhibits POMC CART (discussed in Ghrelin Mechanism of Action), thereby promoting meal initiation and increasing food intake. Whereas leptin...

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...

Assessing Weight History

The pattern of weight change over time in an individual patient often gives important clues as to likely causes of weight gain, past successes and challenges in weight loss, and the reasons that the person is seeking assistance with their weight at this time. Asking questions about the history of weight gain including maximum lifetime weight, factors that were associated with periods of weight gain, and previous periods of weight loss with a focus on events that precipitated previous...

Cannabinoid Receptors

CB1 was the first cannabinoid receptor to be characterized it is found in the central nervous system, adipose tissue, the liver and many other tissues (2,3). CB2 receptors were subsequently identified and are localized mainly in the immune system and they share a 48 homology with CB1 (4-6). Both are 7-transmembrane-spanning G-j o receptors (negatively coupled to adenylyl cyclase and positively coupled to mitogen-activated protein kinase) (3,5). CB1 receptors are also positively coupled to...

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...

Medications That Cause Obesity

Far more common, however, is weight gain associated with the introduction of medications to treat comorbid illnesses (50). These include antidiabetic medications (sulfonylureas, thiazolidinediones, insulin) as well as a wide range of psychotropic medications. The antipsychotic drugs clozapine, olanzepine, risperidone, and quetiapine have all been associated with weight gain, as well as abnormalities in glucose homeo-stasis (51). A number of antidepressant medications, incuding amitriptyline,...

Recast Obesity as a Behavioral Rather than Medical Condition Flip Nexus of Care to Behavioral Professionals

To prevent it, consult a mosquito controller. Documenting the severe medical consequences of obesity can help motivate patients, practitioners, and policy makers to attend to the epidemic. However, despite its numerous and severe physiologic medical sequelae, the origins of obesity (and the recent increase in its prevalence) are largely social and behavioral. This raises questions about our current treatment paradigm. The medical profession has been (perhaps...

Importance Of Evaluating Obesity In Clinical Practice

The prevalence of obesity has increased dramatically over the past 30 yr. From 1985 to 2004, the Centers for Disease Control and Prevention (CDC) determined the prevalence of obesity by self-report across the country through the Behavioral Risk Factor From Contemporary Endocrinology Treatment of the Obese Patient Edited by R. F. Kushner and D. H. Bessesen Humana Press Inc., Totowa, NJ Surveillance System (BRFSS). Despite the fact that self-reported weights underestimate the true prevalence of...

Orexigenic Gut Peptides Ghrelin

Ghrelin, the endogenous ligand for the growth hormone secretagog receptor (GHS-R), was discovered in 1999 (96,97). It is produced from preproghrelin peptide in the oxyntic gland in the fundus of the stomach, but not in the pylorus (97). Ghrelin is also produced, though to a lower extent, in the small and large intestine (96). Various ghrelin variants are produced from alternative splicing, but the mature molecule is a 28-amino-acid peptide with an octanoyl acyl group on its third amino acid...

Defining Pediatric Overweight and Obesity

What is pediatric obesity The Expert Committee on the Evaluation and Treatment of Childhood Obesity has defined pediatric obesity as excess body weight (adipose tissue) associated with adverse health or psychological outcomes (11). BMI is used to assess the presence or risk of overweight. Children among whom the BMI exceeds the 95th percentile for age and gender are considered overweight. Those whose BMI falls between the 85th and 94th percentile for age and gender are considered at risk for...

Possible Mechanisms Underlying Obesity And Diabetes Trends And Disparities

What are the underlying causes for these trends Among researchers there has been an increasing consensus that changes in dietary and physical activity patterns are driven by changes in the environment and by the changing incentives that people face (1,2). Many factors have been suggested as causes of the obesity epidemic and related health disparities automobiles, television, fast food, computer use, vending machines, suburban housing developments, food portion sizes, and countless others....

Medications For Obesity Treatment Approved Medications

Sibutramine is approved by the Food and Drug Administration for long-term use in the treatment of obesity. Sibutramine has been evaluated extensively in several multicenter trials lasting 6 to 24 mo a meta-analysis of some of these trials is shown in Table 2 (10-13). In a 6-mo dose-ranging study of 1047 patients, 67 treated with sibutramine achieved a 5 weight loss from baseline, and 35 lost 10 or more (14). Meta-Analysis of Net Weight Loss With Sibutramine (Placebo Drug) Meta-Analysis of Net...

Poor Timing Of Fat Oxidation In Obesity Glucose Induced Fat Inhibition

More than a decade ago, the author's laboratory began to assess substrate competition in type 2 diabetes and obesity from the perspective of whether fat oxidation is appropriately regulated during fasting conditions. Using arteriovenous limb balance methods to assess oxygen and carbon dioxide exchange across the leg, we observed an elevated RQ across the leg after an overnight fast in type 2 DM (20), which denoted a decreased reliance on fat oxidation. Furthermore, there was reduced fractional...

European Weight Loss Drugs

The DPP allowed the use of drugs in the ILS arm. The drug orlistat was used as a rescue operation in individuals who were unable to achieve their goal or to maintain it over time. At the time (and also at present) the only two drugs that were approved in the United States for long-term weight loss were orlistat and sibutramine. Sibutramine is a norepi-nephrine and serotonin reuptake inhibitor. As a result of its effect on norepinephrine, it has cardiovascular side effects. These include a...

Introduction

The rise and fall of the popularity of low-carbohydrate diets is another indication that the public takes a short-term rather than a long-term approach to weight management. Many people seem willing to try each new popular diet, which usually involves relatively From Contemporary Endocrinology Treatment of the Obese Patient Edited by R. F. Kushner and D. H. Bessesen Humana Press Inc., Totowa, NJ extreme diet changes, and often these diets seem to work for many people at least for a while (1,2)....

Socioeconomic Disparities In Obesity And Diabetes

So far, we have discussed overall trends. At every point in time, obesity and diabetes rates are higher in some populations than in others. Populations with higher rates generally include groups with less education, lower household income, blacks, and Native Americans, but there are some noticeable variations and interactions depending on whether we distinguish between moderate and severe obesity. For example, obesity as defined by a BMI of over 30 has been higher among men than women (although...

Micronutrient Deficiency

Thiamine (vitamin Bj) is absorbed mainly in the jejunum, by both active and passive diffusion. Because the biological half-life of the vitamin is rather short (in the range of 9 to 18 d) and only a small percentage of a high dose is absorbed (27), patients are at risk of developing deficiency syndromes after bariatric surgery. Over the past two decades, numerous case reports of thiamine deficiency have been reported following both restrictive and restrictive-malabsorptive surgeries (28-45). An...

Are Nwcr Participants Different From The Average Person Trying To Lose Weight

One potential criticism of the NWCR is that we have just captured people for whom weight loss is easy and that NWCR participants are somehow different from most overweight and obese people who try to lose weight. Although we cannot conclusively determine whether or not this is the case, we do find that the majority of NWCR participants were overweight as children or adolescents and that most have at least one overweight or obese parent. It is generally thought that those with a family history...

David E Kelley md

History of Concept of Insulin Resistance The Good Side of Glucose-FFA Substrate Competition Metabolic Challenge of Maintaining Macronutrient Balance Poor Timing of Fat Oxidation in Obesity Biochemical Determinants of Metabolic Inflexibility The development of obesity induces resistance to the effect of insulin to stimulate uptake of glucose and suppress release of fatty acids. These metabolic impairments are inter-related and competition between glucose and fatty acids is a key aspect of the...

Indirect Calorimetry to Measure Energy Expenditure

Another tool that can be used clinically to measure energy expenditure is indirect calorimetry. The indirect calorimeter measures air flow and the difference in the concentration of oxygen between inspired and expired air to determine oxygen consumption, which is then used to calculate energy expenditure in kcal h. When measured in the resting state, indirect calorimetry gives an estimate of REE RMR that can be used to estimate daily energy requirements. For most people, total daily energy...

Role Of Allied Health Professionals In Assessment Of The Obese Patient

The evaluation proposed here is extensive. It may be unrealistic to expect a busy clinician to obtain, evaluate, and counsel around all the information that could be discussed with an obese patient. An alternative is to identify individuals with unique skills and specialized resources in the clinical environment who can be brought into service during the evaluation and treatment of these patients. Examples include registered dieticians to assist in evaluation of the diet, exercise physiologists...

Introduction To Adipose Tissue

Adipose tissue (AT) is composed of adipocytes and a diverse population of nonadipocytes that are commonly referred to as stromal-vascular cells (SVC). Adipose tissue has traditionally been considered a passive storage energy depot that serves as a long-term reservoir for fuel stored as triglyceride. However, laboratory, clinical, and epidemiological studies over the past decade have redefined and greatly expanded our understanding of the physiological role of AT. We now appreciate that AT is an...

James O Hill PhD Holly R Wyatt md Suzanne Phelan PhD and Rena RWing PhD

Characteristics of Subjects Predictors of Success in Losing Weight Predictors of Weight-Loss Maintenance Predictors of Weight Regain Are There Lessons to Be Learned from the NWCR Exceptions to Each Weight-Loss Maintenance Strategy Are NWCR Participants Different from the Average Person Trying to Lose Weight What to Do and How to Do It References The National Weight Control Registry (NWCR) is a registry of more than 6000 individuals who have succeeded in long-term weight loss. This is the...

Three Communication Styles Route to Integration

A challenge for practitioners is understanding how to fit MI into their everyday practice. Some view it as a highly specialized skill developed and best delivered by psychologists, which is difficult for the typical physician to integrate effectively. Yet, it is also striking how brief consultations by skilled physicians can approach the spirit and even the letter of MI. One resolution to this intimidation factor, proposed by MI Values List for Counseling Parents of Overweight Children MI...

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...

CNS Regulation of Food Intake

CNS regulation of food intake was originally thought to be controlled by the VMH and the LHA however, several challenges were made to this early hypothesis. The first was a realization that there are limitations to our understanding of the neurocircuitry using the lesions as an experimental approach to understanding CNS function. Conclusions made about larger lesion studies were difficult to interpret because lesions usually destroyed all fibers in the nuclei, not just those fibers of specific...

Angela P Makris phd rd and Gary D Foster phd

Efficacy of Low-Carbohydrate Diets on Weight Loss Efficacy of Low-Carbohydrate Diets on Fasting Lipids Efficacy of Low-Carbohyrate Diets on Imflammatory Biomarkers Efficacy of Low-Carbohydrate Diets on Lipoprotein Subfractions Efficacy of Low-Carbohydrate Diets on Blood Pressure Efficacy of Low-Carbohydrate Diets on Insulin Sensitivity and Glycemic Control Conclusion References Traditionally, the gold standard for obesity treatment has been the combination of a low-fat, low-calorie diet with...

Endocrine Causes of Obesity

Many patients are concerned that they have a metabolic or glandular cause for their obesity. This may be a reflection of the frustration that some of these individuals feel over the difficulties that they have had in battling a weight problem over many years. They may be looking for a medical explanation of why they have not succeeded in their goal of losing weight. Endocrine causes of serious obesity are not common. The three most commonly cited are hypothyroidism, Cushing's syndrome, and...

References

Knochenhauer ES, Key TJ, Kahsar-Miller M, et al. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States a prospective study. J Clin Endocrinol Metab 1998 83(9) 3078 -3082. 2. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935 29 181-191. 3. Yen S,,Vela S, Rankin J. Inappropriate secretion of follicle-stimulating hormone and luteinizing hormone in polycystic ovarian disease. J Clin...

George L Blackburn md PhD and Vivian M Sanchez md

Mechanisms of Action in Weight-Loss Surgery Safety and Effectiveness Conclusion Acknowledgments References Weight-loss surgery is the only effective treatment for severe, medically complicated, and refractory obesity. It reverses, eliminates, or significantly ameliorates numerous life-threatening medical comorbidities that occur as part of the pathophysiology of obesity. Rapid changes in surgical technology and in demand for weight-loss surgery have made the field one of medicine's most...

Function as Retrograde Neurotransmitter

Many CNS CB1 receptors are localized presynaptically on GABAergic interneurons (33,38). Endocannabinoids released from postsynaptic membranes therefore must diffuse or be transported retrogradely, back across the synaptic cleft, in order to interact with CB1 and thereby decrease the release of presynaptic neurotransmitter, as diagrammed in Fig. 2. The generally accepted model is that when electrical activity in the form of repeated action potentials and consequent depolarization in the...

Leanne M Redman PhD and Eric Ravussin PhD

Methods of Measuring Energy Expenditure Components of Energy Expenditure and Their Relevance to Obesity Energy Expenditure in the Etiology of Obesity Energy Expenditure in Children Molecular Mechanisms of Energy Expenditure Variability Body weight is dependent on an intricate balance between energy intake and energy expenditure. When energy intake exceeds energy expenditure weight is gained, and the majority of this excess energy is stored as body fat. Whether the culprit of weight gain is...

Romana Dmitrovic md and Richard S Legro md

Oligomenorrhea Amenorrhea Hyperandrogenemia Hyperandrogenism Polycystic Ovaries on Ultrasound Long-Term Consequences Polycystic ovary syndrome (PCOS) is a common but poorly understood endocrinopathy diagnosed by the combination of oligomenorrhea, hyperandrogenism, and polycystic ovaries. Many of the women with PCOS are also uniquely and variably insulin-resistant. This can manifest as hyperinsulinemia, glucose intolerance, and frank diabetes. Affected women are plagued by infertility, menstrual...

History Of Concept Of Insulin Resistance

If it can be argued that there is ambiguity concerning whether substrate competition is always adverse for metabolism or whether it is glucose or FFA that causes problems, then this note of ambiguity might also be extended to a consideration of IR itself. Insulin resistance has been an enigma since it was initially described 75 yr ago (1). It is customary that a pathophysiological process like IR is regarded as a mechanism of disease. But there is another perspective. There is an emerging body...

Ciliary Neurotrophic Factor and Axokine

Ciliary neurotrophic factor (CNTF) is a neuronal survival factor shown to induce weight loss in rodents and humans (222,223). CNTF leads to a reduction in food intake and body weight apparently via activating pathways that mimic leptin, though unlike leptin, CNTF is active in leptin-resistant diet-induced obese mice (224). Interestingly, CNTF-treated rodents and humans lose weight and maintain the reduced body weight for a long period after cessation of treatment. The implication of these...

Drugs No Longer Under Investigation or Withdrawn

Short-term studies with phenylpropanolamine were reviewed in 1992 weight loss was similar to the short-term weight loss seen with prescription obesity drugs (113). The longest study of phenylpropanolamine lasted 20 wk. There was a 5.1-kg weight loss in the drug group and 0.4-kg weight loss in the placebo group, meeting the FDA criteria for a prescription weight loss drug of a greater than 5 weight loss compared with placebo (114). Although phenylpropanolamine had a long history of safety in...

Acetyl CoA Carboxylase

Acetyl CoA carboxylase (ACC), which exists in at least two isoforms in humans, is responsible for synthesizing malonyl coenzyme A, a potent inhibitor of fatty acid oxi dation. ACC1 is expressed mainly in lipogenic tissue such as liver and adipose, and ACC2 in the heart and skeletal muscle (148). In humans both isoforms have central roles in fatty acid biosynthesis and oxidation (149). Although mice lacking ACC1 die young, the ACC2-null mice have a normal life span and, compared with wild-type...

George A Bray md and Frank L Greenway md

Algorithm for Using Currently Available Drugs Medications for Obesity Treatment Conclusions References Obesity is increasing in prevalence and its medical liabilities are largely related to central adiposity and the associated insulin resistance. The present drugs available for the treatment of obesity and metabolic syndrome are few in number and limited in efficacy. This chapter reviews the drugs approved by the US Food and Drug Administration (FDA) to treat obesity, drugs approved by the FDA...

Neuroregulation of Appetite

Benoit, PhD, and Deborah J. Clegg, PhD Central Signals Related to Energy Homeostasis This chapter reviews current literature on hormonal and neural signals critical for the regulation of individual meals and body fat. Body weight is regulated via an ongoing process called energy homeostasis, or the long-term matching of food intake to energy expenditure. Reductions from an individual's normal weight owing to a lack of sufficient food lowers levels of adiposity...

Magnetic Resonance Spectroscopy Quantification of Ectopic

Unlike CT or MRI, proton magnetic resonance spectroscopy (H1 MRS) is able to partition the lipid signal into separate intra- and extramyocellular lipid (IMCL and EMCL) components within the skeletal muscle. As it has been suggested that IMCL is an important fat depot that is associated with deleterious effects on insulin sensitivity, it may be important to accurately quantify this depot. Briefly, the principles of MRS are very similar to those of MRI, and in many cases MRS can be acquired using...

Corticotropin Releasing Hormone and Urocortin

Corticotropin-releasing hormone (CRH) is synthesized in the PVN and LHA and is negatively regulated by levels of glucocorticoids. CRH is a key controller of the hypo-thalamic-pituitary axis (HPA), which regulates glucocorticoid secretion from the adrenal gland. Administration of CRH into the ventricular system potently reduces food intake, increases energy expenditure, and reduces body weight (195,196). As previously mentioned, when animals are overfed, they voluntarily reduced their food...

Adiponectin

Adiponectin, also called gelatin-binding protein (GBP)28 (19), adipocyte complement-related protein (Acrp30) (20), AdipoQ (21), and adipose most abundant gene transcript 1 (apMI) (22), was discovered at approximately the same time as leptin, in 1995. Similar to leptin, adiponectin is expressed exclusively by mature adipocytes, and increases dramatically with differentiation of preadipocytes to adipocytes (23). However, unlike leptin, its expression does not increase with obesity, but as will be...

Insulin Sensitizing Agents

Drugs developed initially to treat type 2 diabetes have also been utilized to treat PCOS. None of these agents are currently FDA-approved for the treatment of PCOS or for related symptoms such as anovulation, hirsutism, or acne. These include metformin (117-119), thiazolidinediones, and an experimental insulin sensitizer drug, d-chiro-inositol (120). Metformin was approved for the treatment of type 2 diabetes by the FDA in 1994, but was used clinically for almost 20 yr before that in other...

Prenatal Influences on Offspring

It is not surprising that major alterations in the metabolic milieu in which a fetus grows can markedly affect its development. Cross-fostering studies in which pups are placed with surrogate dams shortly after birth suggest that prenatal factors account for 61 to 96 of the variance in body weight gain in male and 35 to 92 in female offspring (68). Offspring of dams fed a high-fat diet during gestation became more obese than those whose dams were fed a low-fat diet, even if the high-fat...

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...

Catabolic Effector Systems

Catabolic systems are those that are activated during positive energy balance. These systems oppose those previously described, which are activated during negative energy balance. When animals or humans consume calories in excess of their requirements, body weight is gained. Additionally, if animals are forced to consume calories in excess of their needs, voluntary food intake drops to near zero and the animals gain body weight (187,188). These data provide further evidence that body weight is...