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...

What Is Energy Density

Energy density is the amount of energy in a particular weight of food. It is generally presented as the number of calories in a gram (kcal g). Foods with a low energy density provide less energy relative to their weight than foods with a high energy density. Therefore, for the same amount of energy, a larger, more satisfying portion size of food can be consumed of a food low in energy density, compared with a food high in energy density. Energy density values, which are influenced by the...

Nicole H Rogers MS Martin S Obin PhD and Andrew S Greenberg md

Inflammatory Alterations in Adipose Tissue With Obesity Role of Regional Adipose Tissue Depots in Metabolism Pathology-Associated Changes in Adipokines Conclusion References Adipose tissue (AT) is composed of adipocytes and a diverse population of nonadipocytes that are commonly referred to as stromal-vascular cells. Adipose tissue has traditionally been considered a passive storage energy depot that, indeed, does serve as a long-term reservoir for fuel stored as triglyceride. However,...

The Endocannabinoid System

The endocannabinoid system includes cannabinoid receptors called CB1 and CB2 that are located on cell membranes, along with the endogenous ligands that bind to them and the enzymes that synthesize, degrade, and or reuptake the ligands. Key ligands include the endogenous agonists anandamide and 2-arachidonoyl-glycerol 2-AG . Exogenous compounds can also access and bind to the same receptors, and numerous plant-derived and synthetic CB1 and CB2 agonists and antagonists are available for research...

Drugs on the Near and Distant Horizons

Rimonabant is an orally active antagonist at the cannabinoid-1 receptor that is in the late stages of development, with approval by the FDA and a launch anticipated in 2006. The development of axokine has been terminated. Pramlintide and exenatide have been recently approved for the treatment of diabetes. Both these drugs give weight loss. There are other drugs in phase II, phase I, and earlier in development. There is less information about these compounds, but they generally fall into one of...

John M Jakicic phd Amy D Otto phd rd ldn Kristen Polzien phd and Kelli K Davis ms

Contribution of Physical Activity to Total Energy Expenditure Can Physical Activity Prevent Weight Gain Physical Activity for Weight Loss and Prevention of Weight Regain Development of Exercise Prescription for Weight Control Conclusion Acknowledgments References There is an increasing prevalence of overweight and obesity in the United States and other developed countries. This can have significant public health implications because of the association of excess body weight with increased risk...

CNS Regulation by Adiposity Signals and Effector Pathways

These challenges to the dual-centers hypothesis led to new models for understanding the role of the hypothalamus in the control of food intake. Other research has focused on emphasizing factors and signaling pathways that control long-term energy balance. Adult mammals typically match their caloric intake to their caloric expenditure in a remarkably accurate fashion. In the 1950s Kennedy postulated that animals could regulate their energy balance by monitoring the major form of energy storage...

Pericardial

Another emerging depot of potential interest is pericardial fat, the fat depot that lies within the pericardial sac surrounding the heart. In human studies this fat depot is associated with increased risk for coronary artery disease 126,127 , and may be a source of production for several inflammatory cytokines, which themselves are established antecedents for disease 128 . In animal models, increases in the size of the fat pads around the heart have been shown to increase ventricular stiffness...

Treatment of Infertility

Clomiphene citrate CC has traditionally been the first-line treatment agent for infertility in women with PCOS. It is a nonsteroidal agent and a member of a large family of triphenylethylene derivatives, which includes clorotrianisene and tamoxifen both of which compare favorably to CC in inducing ovulation . It is a racemic mixture of two isomers, zuclomiphene longer-acting and enclomiphene more potent in inducing ovulation 140 . Clomiphene has a long half-life only 51 of the oral dose is...