Effective Therapy For Obesity Research Articles

Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases.

The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system. Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities. Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).

Bariatric surgery and long-term nutritional issues.

Bariatric surgery is recognized as a highly effective therapy for obesity since it accomplishes sustained weight loss, reduction of obesity-related comorbidities and mortality, and improvement of quality of life. Overall, bariatric surgery is associated with a 42% reduction of the cardiovascular risk and 30% reduction of all-cause mortality. This review focuses on some nutritional consequences that can occur in bariatric patients that could potentially hinder the clinical benefits of this therapeutic option. All bariatric procedures, to variable degrees, alter the anatomy and physiology of the gastrointestinal tract; this alteration makes these patients more susceptible to developing nutritional complications, namely, deficiencies of macro- and micro-nutrients, which could lead to disabling diseases such as anemia, osteoporosis, protein malnutrition. Of note is the evidence that most obese patients present a number of nutritional deficits already prior to surgery, the most important being vitamin D and iron deficiencies. This finding prompts the need for a complete nutritional assessment and, eventually, an adequate correction of pre-existing deficits before surgery. Another critical issue that follows bariatric surgery is post-operative weight regain, which is commonly associated with the relapse of obesity-related co-morbidities. Nu-tritional complications associated with bariatric surgery can be prevented by life-long nutritional monitoring with the administration of multi-vitamins and mineral supplements according to the patient’s needs.

Mesenchymal stromal cell-based therapies reduce obesity and metabolic syndromes induced by a high-fat diet

Obesity is an alarming global health problem that results in multiaspect metabolic syndromes in both genders and most age groups. The lack of effective therapies for obesity and its associated metabolic syndrome is an urgent societal issue. To elucidate whether mesenchymal stromal cell (MSC)-based therapies can ameliorate high-fat diet-induced obesity and compare the effectiveness of several methodological approaches, we transplanted human MSCs, MSC-derived brown adipocytes (M-BA), and MSC lysateinto obese mice. All 3 MSC-based treatments improved obesity-associated metabolic syndromes including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, glucose intolerance, and inflammation in obese mice after repeated administration for10weeks. MSC-based treatments altered the ratio of adiponectin to leptinand regulated the expression of Pparα and Pparγ, which are involved in maintaining energy homeostasis, in major metabolic tissues. Among treatments, M-BA showed the strongest beneficial effect. Importantly, M-BA administrationnot only reduced obesity-associated metabolic syndromes but also reduced body weight and hyperlipidemia, indicating that it is an effective therapyfor obesity. Together, our findings revealed the therapeutic potential of MSCs for the treatment of metabolic syndrome.

Endoscopic Sleeve Gastroplasty Alters Gastric Physiology andInduces Loss of Body Weight in Obese Individuals.

Although bariatric surgery is the most effective therapy for obesity, only a small proportion of candidates undergo this surgery. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure that reduces the size of the gastric reservoir. We investigated its durability and effects on body weight and gastrointestinal function in a prospective study of obese individuals. Twenty-five obese individuals (21 female; mean body mass index, 35.5 ± 2.6 kg/m2; mean age, 47.6 ± 10 years) underwent ESG with endoluminal creation of a sleeve along the gastric lesser curve from September 2012 through March 2015 at the Mayo Clinic in Rochester, Minnesota. Subjects were followed for a median period of 9 months. We measured changes in body weight and recorded adverse events; patients were assessed by endoscopy after 3 months. Four participants underwent pre-ESG and post-ESG analyses to measure solid and liquid gastric emptying, satiation (meal tolerance), and fasting and postprandial levels of insulin, glucose, and gut hormones. Subjects had lost 53% ± 17%, 56% ± 23%, 54% ± 40%, and 45% ± 41% of excess body weight at 6,9, 12, and 20 months, respectively, after the procedure (P < .01). Endoscopy at 3 months showed intact gastroplasty in all subjects. After ESG, physiological analyses of 4 participants showed a decrease by 59% in caloric consumption to reach maximum fullness (P= .003), slowing of gastric emptying of solids (P= .03), and a trend toward increased insulin sensitivity (P= .06). Three patients had serious adverse events (a perigastric inflammatory collection, a pulmonary embolism, and a small pneumothorax) but made full recoveries with no need for surgical interventions. No further serious adverse events occurred after the technique was adjusted. ESG delays gastric emptying, induces early satiation, and significantly reduces body weight. ESG could be an alternative to bariatric surgery for selected patients with obesity. ClincialTrials.gov number: NCT01682733.

The nutritional composition and anti-obesity effects of an herbal mixed extract containing Allium fistulosum and Viola mandshurica in high-fat-diet-induced obese mice

Obesity is a serious public health issue and plays a critical role in the pathogenesis of hypertension, dyslipidemia, and diabetes [1]. This study investigated the nutritional composition and anti-obesity effects of an herbal extract containing Allium fistulosum and Viola mandshurica (AFE+VME) in high-fat-diet (HFD)-induced obese mice. In traditional oriental medicine, A. fistulosum and V. mandshurica are considered to be effective in promoting blood circulation to remove blood stasis [2]. The nutritional analysis revealed that this mixed extract is high in carbohydrate (72.2 g/100 g) and protein (11.5 g/100 g); low in fat (1.7 g/100 g); rich in vitamins E (4.8 mg/100 g), B1 (14.8 mg/100 g), B2 (1.0 mg/100 g), niacin (7.9 mg/100 g), and folic acid (1.57 mg/100 g); and rich in minerals such as calcium (600 mg/100 g), iron (106.1 mg/100 g), and zinc (5.8 mg/100 g). The oral administration of AFE+VME in mice reduced body weight, tissue weight, adipocyte size, and lipid accumulation in the liver compared with HFD control mice. AFE+VME also decreased serum triglyceride, total cholesterol, and leptin concentrations. Furthermore, AFE+VME markedly increased the mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), uncoupling protein-2 (UCP-2), and adiponectin and decreased leptin expression in the epididymal adipose tissue. Our results suggest that the extract containing A. fistulosum and V. mandshurica improved lipid metabolism via the up-regulation of PPAR-γ, UCP-2, and adiponectin expression and the down-regulation of leptin in HFD-induced obese mice. Therefore, the extract containing A. fistulosum and V. mandshurica may be a potentially effective therapy for obesity and its related metabolic disorders.

The nutritional composition and anti-obesity effects of an herbal mixed extract containing Allium fistulosum and Viola mandshurica in high-fat-diet-induced obese mice.

BackgroundIn traditional oriental medicine, A. fistulosum and V. mandshurica are considered to be effective in promoting blood circulation. Therefore, in this study, we investigated whether a solution containing both A. fistulosum and V. mandshurica (AFE + VME) extracts has synergistic effects on the treatment of hyperlipidemia and obesity.MethodsAnti-obesity effects of an herbal extract containing Allium fistulosum and Viola mandshurica (AFE + VME) were investigated in high-fat diet (HFD)-induced obese mice. AFE + VME was orally administrated to mice with the HFD at a dose of 200 mg/kg/day for 8 weeks. We observed the effects of mixed extract on body weight, fat mass, serum lipid levels, and mRNA expression levels of lipid metabolism-related genes in the adipose tissue of mice.ResultsThe nutritional analysis revealed that this mixed extract is high in carbohydrate (72.2 g/100 g) and protein (11.5 g/100 g); low in fat (1.7 g/100 g); rich in vitamins E (4.8 mg/100 g), B1 (14.8 mg/100 g), B2 (1.0 mg/100 g), niacin (7.9 mg/100 g), and folic acid (1.57 mg/100 g); and rich in minerals such as calcium (600 mg/100 g), iron (106.1 mg/100 g), and zinc (5.8 mg/100 g). The oral administration of AFE + VME in obese mice reduced body weight, tissue weight, adipocyte size, and lipid accumulation in the liver compared with HFD control mice. AFE + VME also decreased serum triglyceride, total cholesterol, and leptin concentrations. Furthermore, AFE + VME markedly increased the mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), uncoupling protein-2 (UCP-2), and adiponectin and decreased leptin expression in the epididymal white adipose tissue. Our results suggest that the extract containing A. fistulosum and V. mandshurica improved lipid metabolism via the up-regulation of PPAR-γ, UCP-2, and adiponectin expression and the down-regulation of leptin in HFD-induced obese mice.ConclusionsTherefore, the extract containing Allium fistulosum and Viola mandshurica may be a potentially effective therapy for obesity and its related metabolic disorders such as hyperlipidemia and insulin resistance.

Mo1524 Endoscopic Sleeve Gastroplasty Using a Modified Plication Method for Weight Loss

Bariatric surgery is the most effective therapy for obesity and metabolic syndrome. Emerging endoscopic techniques such as endoscopic sleeve gastroplasty are minimally invasive and can mimic the anatomic alterations achieved by surgical sleeve gastrectomy.

A novel chemical uncoupler ameliorates obesity and related phenotypes in mice with diet-induced obesity by modulating energy expenditure and food intake

Decreasing mitochondrial coupling efficiency has been shown to be an effective therapy for obesity and related metabolic symptoms. Here we identified a novel mitochondrial uncoupler that promoted uncoupled respiration in a cell type-specific manner and investigated its effects on modulation of energy metabolism in vivo and in vitro. We screened a collection of mitochondrial membrane potential depolarising compounds for a novel chemical uncoupler on isolated skeletal muscle mitochondria using a channel oxygen system. The effect on respiration of metabolic cells (L6 myotubes, 3T3-L1 adipocytes and rat primary hepatocytes) was examined and metabolic pathways sensitive to cellular ATP content were also evaluated. The chronic metabolic effects were investigated in high-fat diet-induced obese mice and standard diet-fed (SD) lean mice. The novel uncoupler, CZ5, promoted uncoupled respiration in a cell type-specific manner. It stimulated fuel oxidation in L6 myotubes and reduced lipid accumulation in 3T3-L1 adipocytes but did not affect gluconeogenesis or the triacylglycerol content in hepatocytes. The administration of CZ5 to SD mice increased energy expenditure (EE) but did not affect body weight or adiposity. Chronic studies in mice on high-fat diet showed that CZ5 reduced body weight and improved glucose and lipid metabolism via both increased EE and suppressed energy intake. The reduced adiposity was associated with the restoration of expression of key metabolic genes in visceral adipose tissue. This work demonstrates that a cell type-specific mitochondrial chemical uncoupler may have therapeutic potential for treating high-fat diet-induced metabolic diseases.

Bariatric surgery: a cure for diabetes?

To review the basic mechanisms of caloric intake reduction of bariatric surgery and its clinical and metabolic outcomes. To describe novel bariatric procedures, their effects on glucose homeostasis and insulin sensitivity and to explain the proposed mechanisms for type 2 diabetes mellitus (T2DM) resolution. The effects of surgically induced weight loss on T2DM have elucidated in part the role of proximal and distal gastrointestinal bypass on insulin sensitivity. A dual mechanism for improvement in glucose homeostasis after bariatric surgery has been proposed that appears to be weight loss independent. Bariatric surgery is the most effective therapy for obesity and obesity-related comorbidities today that provide high rates of resolution of T2DM with improvements in insulin resistance and β-cell function. Novel bariatric procedures offer a unique opportunity to understand the pathophysiology of T2DM and to identify potential pharmacologic targets for effective T2DM treatments and a potential cure.

Decreased dopamine type 2 receptor availability after bariatric surgery: Preliminary findings

Background: Diminished dopaminergic neurotransmission contributes to decreased reward and negative eating behaviors in obesity. Bariatric surgery is the most effective therapy for obesity and rapidly reduces hunger and improves satiety through unknown mechanisms. We hypothesized that dopaminergic neurotransmission would be enhanced after Roux-en-Y-Gastric Bypass (RYGB) and Vertical Sleeve Gastrectomy (VSG) surgery and that these changes would influence eating behaviors and contribute to the positive outcomes from bariatric surgery. Methods: Five females with obesity were studied preoperatively and at ∼ 7 weeks after RYGB or VSG surgery. Subjects underwent positron emission tomography (PET) imaging with a dopamine type 2 (DA D2) receptor radioligand whose binding is sensitive to competition with endogenous dopamine. Regions of interest (ROI) relevant to eating behaviors were delineated. Fasting enteroendocrine hormones were quantified at each time point. Results: Body weight decreased as expected after surgery. DA D2 receptor availability decreased after surgery. Regional decreases (mean ± SEM) were caudate 10 ± 3%, putamen 9 ± 4%, ventral striatum 8 ± 4%, hypothalamus 9 ± 3%, substantia nigra 10±2%, medial thalamus 8±2%, and amygdala 9 ± 3%. These were accompanied by significant decreases in plasma insulin (62%) and leptin (41%). Conclusion: The decreases in DA D2 receptor availability after RYGB and VSG most likely reflect increases in extracellular dopamine levels. Enhanced dopaminergic neurotransmission may contribute to improved eating behavior (e.g. reduced hunger and improved satiety) following these bariatric procedures.

Brown Fat in Humans: Turning up the Heat on Obesity

The looming pandemic of obesity and overweight, driven by ready access to high-calorie food and an increasingly sedentary way of life, poses a severe threat to global public health. The pathological accumulation of excess dysfunctional adipose tissue that characterizes obesity is a major risk factor for many other diseases, including type 2 diabetes, cardiovascular disease, hypertension, stroke, arthritis, and various types of cancer (1). A basic, but often misunderstood, concept is that weight gain is caused by a fundamental energy imbalance, when energy intake from food chronically exceeds energy expended by physical activity and metabolic processes (Fig. 1). Humans have evolved efficient biological mechanisms to acquire and defend their energy stores. A therapy for weight loss must, therefore, involve a decrease in food intake and/or an increase in energy expenditure. FIG. 1. BAT contributes to energy expenditure. Weight gain and obesity are caused by chronic periods of positive energy balance. Energy intake comes from food consumption, whereas the major contributors to expenditure are exercise and basic metabolic processes. The studies reviewed here suggest that BAT activity could impact daily energy expenditure. BAT dissipates energy as heat and can thus counteract weight gain. Interindividual variability in the amount or function of this tissue may impact body weight. In addition, therapeutic expansion/activation of this tissue may prove to be an effective therapy for obesity. WAT, white adipose tissue. In addition to the better-known white adipose tissue that specializes in lipid storage and undergoes pathological expansion during obesity, mammals are also equipped with thermogenic brown adipose tissue (BAT). BAT evolved in mammals to dissipate large amounts …

Arginine metabolism and nutrition in growth, health and disease

L-Arginine (Arg) is synthesised from glutamine, glutamate, and proline via the intestinal-renal axis in humans and most other mammals (including pigs, sheep and rats). Arg degradation occurs via multiple pathways that are initiated by arginase, nitric-oxide synthase, Arg:glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine, and agmatine with each having enormous biological importance. Arg is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system. There is compelling evidence that Arg regulates interorgan metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that Arg is a nutritionally essential amino acid (AA) for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics. Moreover, a growing body of evidence clearly indicates that dietary supplementation or intravenous administration of Arg is beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver and immune functions, as well as facilitating wound healing, enhancing insulin sensitivity, and maintaining tissue integrity. Additionally, Arg or L-citrulline may provide novel and effective therapies for obesity, diabetes, and the metabolic syndrome. The effect of Arg in treating many developmental and health problems is unique among AAs, and offers great promise for improved health and wellbeing of humans and animals.

Anti‐obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid

Obesity has become a prevailing epidemic throughout the globe. Effective therapies for obesity become attracting. Food components with beneficial effects on "weight loss" have caught increasing attentions. Conjugated linoleic acid (CLA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) belong to different families of polyunsaturated fatty acids (PUFA). However, they have similar effects on alleviating obesity and/or preventing from obesity. They influence the balance between energy intake and expenditure; and reduce body weight and/or fat deposition in animal models, but show little effect in healthy human subjects. They inhibit key enzymes responsible for lipid synthesis, such as fatty acid synthase and stearoyl-CoA desaturase-1, enhance lipid oxidation and thermogenesis, and prevent free fatty acids from entering adipocytes for lipogenesis. PUFA also exert suppressive effects on several key factors involved in adipocyte differentiation and fat storage. Despite their similar effects and shared mechanisms, they display differences in the regulation of lipid metabolism. Moreover, DHA and EPA exhibit "anti-obesity" effect as well as improving insulin sensitivity, while CLA induces insulin resistance and fatty liver in most cases. A deeper and more detailed investigation into the complex network of anti-obesity regulatory pathways by different PUFA will improve our understanding of the mechanisms of body weight control and reduce the prevalence of obesity.

ELECTROACUPUNCTURE TREATMENT OF OBESITY WITH PSYCHOLOGICAL SYMPTOMS

The aim was to study the effect of placebo EA, electroacupuncture (EA), and diet on obesity and accompanying psychological symptoms. One hundred and sixty-five volunteer women participated in the study. There were three groups: (i) Placebo EA, (ii) EA, and (iii) diet restriction group. EA was performed by using three ear and six body points. There was a 4.8% reduction in weight of patients with EA application, whereas patients with a diet restriction and placebo EA had a 2.5% and 2.7% weight reduction, respectively. There were significant decreases in phobia, anger, anxiety, obsession, paranoid symptoms, and depression in the EA groups compared to those of the placebo EA and diet groups. It was suggested that electroacupuncture may be an effective therapy for obesity including the psychological signs and symptoms in women.

DIETARY THERAPY FOR OBESITY IS A FAILURE AND PHARMACOTHERAPY IS THE FUTURE: A POINT OF VIEW

1. We confront an escalating epidemic of obesity. The precipitating factors are undoubtedly environmental and include increasingly immobilizing occupations and technologies and an abundance of food in many societies. This understanding has led to the view that the obesity epidemic is entirely environmental and that obesity should be treated primarily by behavioural (particularly dietary) therapy. That is, a prominent view is that common human obesity is an environmental disease and is not, like hypertension and hypercholesterolaemia, a complex, multifactorial disease resulting from the interaction of genetic and environmental variance. 2. In the first part of the present article, I argue that this view has obscured a strong genetic-biological contribution to body mass and adiposity in humans. This is supported by studies of adopted children and twins and by rare Mendelian forms of human obesity. 3. In the second part of the present article, I argue that behavioural therapy for maintenance of weight loss is, overall, a failure. The overwhelming majority of people who lose weight by dieting regain it in several years. Many have blamed this on patients' lack of will-power and discipline, but there is mounting evidence that biological mechanisms contribute substantially to relapse from weight loss during dietary therapy. These include a compensatory decrease in energy expenditure during dieting and compensatory adaptations that would be expected to increase appetite. 4. We live in an era of evidence-based medicine; the evidence does not support the efficacy of diet therapy for maintenance of weight loss in obesity. This has been true for decades, despite efforts to improve behavioural therapy. Despite what we want to happen, this will not likely improve, because the failure of diet therapy for the maintenance of weight loss in obesity is probably primarily biological, not behavioural. 5. In the third part of the article, I argue that drugs will increasingly dominate the treatment of obesity. We are in the midst of a revolution in understanding the biological regulation of appetite and metabolism that began with the pioneering discovery of leptin. In my judgement, this will lead inevitably to the development of safe, effective therapy for obesity. 6. This transformation from behavioural to pharmacological therapy proved true with hypertension and hypercholesterolaemia. Pharmacological therapy for hypertension and hypercholesterolaemia followed the discovery of the pathways regulating arterial pressure and cholesterol biosynthesis, respectively, and behavioural therapy for these diseases is now secondary. Despite the skepticism, I predict that the same transformation will occur in the treatment of obesity. This is not to argue against the need for environmental modification to slow the escalating epidemic of obesity, but it is to suggest that future effective treatment of common human obesity should recognize the limitations of dietary therapy for maintenance of weight loss and the promise of pharmacological therapy.

Peptide YY Levels Are Elevated After Gastric Bypass Surgery

Mechanisms that promote effective and sustained weight loss in persons who have undergone Roux-en-Y gastric bypass surgery are incompletely understood but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut-derived hormone with anorectic properties. We sought to determine whether gastric bypass surgery alters PYY levels or response to glucose. PYY and ghrelin levels after a 75-gram oral glucose tolerance test were measured in 6 morbidly obese patients 1.5 +/- 0.7 (SE) years after gastric bypass compared with 5 lean and 12 obese controls. After substantial body weight loss (36.8 +/- 3.6%) induced by gastric bypass, the PYY response to an oral glucose tolerance test was significantly higher than in controls (p = 0.01). PYY increased approximately 10-fold after a 75-gram glucose load to a peak of 303.0 +/- 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly higher than fasting levels for all subsequent time-points. In contrast, PYY levels in obese and lean controls increased to a peak of approximately 2-fold, which was only borderline significant. Ghrelin levels decreased in a symmetric but opposite fashion to that of PYY. Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut-derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY(3-36) replacement could represent an effective therapy for obesity.

Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Sibutramine in Obese Hypertensive Patients

Objectives: To compare weight loss efficacy, safety and tolerability of sibutramine and placebo in mildly to moderately obese hypertensive subjects; to assess the effect of weight loss on blood pressure. Design: Randomized, double-blind, parallel-group; 3-week placebo run-in and 12-week treatment phase. Setting: Nine hospital outpatient clinics and general practices in the Netherlands. Participants: 127 men and women, 18–65 years old, with body mass indices (BMI) ranging from 27 to 40 kg/m² and stabilized hypertension – mean resting diastolic blood pressure of 90–120 mm Hg – with or without antihypertensive medication. Interventions: Sibutramine 10 mg once daily; placebo. Main outcome measures: Body weight, blood pressure, routine laboratory and clinical safety monitoring. Results: Of 113 evaluable patients, 54 received sibutramine and 59 placebo. Weight reduction was significantly greater with sibutramine from week 2 onwards (last observation carried forward): mean, 4.4 kg with sibutramine and 2.2 kg with placebo (p = 0.002); mean percentage weight reduction, 4.7 and 2.3%, respectively (p < 0.001); mean BMI reduction, 1.6 and 0.8 kg/m², respectively (p < 0.01). Reduction in excessive body weight was associated with a reduction in blood pressure in both groups, although the mean reduction in supine diastolic blood pressure was numerically, but not statistically significantly, greater in the placebo group (5.7 mm Hg) compared with the sibutramine group (4.0 mm Hg; p = 0.21). Similar reductions were seen in supine systolic blood pressure. Both treatments were well tolerated. Conclusions: Sibutramine 10 mg once daily is a useful, effective therapy for obesity in the presence of stable hypertension.

The Pathophysiology of Obesity

Effective therapy for obesity would result in an improved quality of life and possibly even an increased life expectancy for many individuals. To understand why current therapy for obesity is inadequate, it is necessary to review what is known about the regulation of body composition. In individuals of normal weight, energy balance is maintained at a body fat content of less than 25% by adjustments in both energy intake and energy expenditure. Obese individuals are able to achieve long-term energy balance only at a higher body fat content. Both obese and normal weight individuals respond to any deviation of body fat content from its customary value with counterregulatory changes in energy expenditure and appetite. This review will elaborate upon these observations both to explain the limitations of current weight loss therapy and to suggest a strategy for targeting available therapy until the physiology of energy balance is better understood.

Pharmacological approaches to treating the obese patient

It should be obvious from the foregoing discussion that, at the present time, there is not an acceptably safe and effective pharmacological treatment for obesity. This patent inadequacy of present drug regimens has spawned the investigation into the diverse pharmacological approaches reviewed in this paper as well as investigation into the intestinal bypass operation (see Chapter 10). We feel that the eventual, safe and effective therapy for obesity will come from the pharmacological realm. Glucose-blocking drugs, growth hormone analogues, and hydroxycitrate are but three of the potentially safe and effective approaches to the problem for the future. It will be truly fascinating to watch the development in the treatment of obesity and, specifically, the pharmacological treatment for this problem over the next five to ten years.