A survey of opinions on the causes of and effectiveness for treatment of obesity was carried out on data provided by questionnaires from 57 physicians and scientists involved in obesity research. Responses were grouped by region (Europe, North America, and South America), gender, age (30-50 and over 50 years), and professional training (MD or PhD). Metabolic factors were considered the most important cause of obesity overall with physical inactivity only slightly behind. There were no gender differences, but the older group thought physical inactivity was a more important cause than the younger group. Weight cycling overall was not considered very important, although it was significantly more important among the Ph.D. group. Low-fat diets were considered the most effective treatment, with the older group of respondents rating low-fat diet more highly than their younger colleagues. Exercise was viewed as a more important treatment among North Americans, and medications as less in the treatment of obesity. All groups viewed serotonergic and thermogenic drugs as the most effective treatments whose usefulness would increase during the next 10 years.

Age Factors↗

PubMed1995

Evaluation of drugs for treating obesity.

Criteria for the evaluation of new drugs to treat obesity are important as guides for designing clinical trials to test these agents. These criteria must be developed in relation to the realities of obesity, which is a chronic disease associated with morbidity and mortality that is increased by visceral fat deposits. The observation that patients regain weight after stopping drug treatment for obesity argues for the proposition that drugs work only when taken and NOT that the drugs are ineffective. The analogy between the development of treatments for obesity to those for the treatment of hypertension is used to highlight potential areas for new developments. Several features of an ideal drug for the treatment of obesity are suggested. Criteria for evaluating new drugs include both primary and secondary endpoints. The primary endpoint for an anti-obesity drug should be weight loss, possibly by category of success. Losses of total body fat or visceral fat might be alternative primary endpoints. Secondary endpoints include reduction in risk factors for associated diseases and improvement in the quality of life. In trials where vigorous placebo designs including highly aggressive behavior modification or very-low-calorie diets were used, it may be difficult or impossible to detect a response to a drug.

Appetite Depressants↗

PubMed1995

Sibutramine: a novel new agent for obesity treatment.

Sibutramine is a novel new pharmacologic agent which is a specific reuptake inhibitor for norepinephrine and serotonin. Preclinical data show that sibutramine and its two metabolites reduce food intake of animals eating either high or low carbohydrate diets and of obese Zucker rats. An 8-week clinical trial showed a dose-dependent decrease on body weight. Sibutramine, 5 and 20 mg/day, produced a dose-related weight loss in obese subjects compared to placebo in an 8-week trial. In doses varying from 1 to 30 mg, sibutramine also produced a dose-dependent decrease in weight in the healthy obese population when used in 6-,8-,12-24- and 52-week trials. Although the majority of the weight loss occurred during the first 12 weeks of treatment, weight loss had not plateaued in by 24 weeks in the higher doses. Side effects were mild. This drug shows promise as an antiobesity drug.

Adolescent↗

PubMed1995

Topical fat reduction.

The fat on women's thighs is more difficult to mobilize due to increased alpha-2 adrenergic receptor activity induced by estrogen. Lipolysis can be initiated through adipocyte receptor stimulation (beta adrenergic) or inhibition (adenosine or alpha-2 adrenergic) or by inhibition of phosphodiesterase. Since many women desire regional thigh fat loss, a series of clinical trials were initiated using one thigh as a double-blinded control. Trial #1: Five overweight women had injections of isoproterenol at intervals around the thigh three times a week for 4 weeks with diet and walking. Trial #2: Five overweight woman had ointment containing forskolin, yohimbine and aminophylline applied to the thigh five times a week for 4 weeks after hypertonic warm soaks with a diet and walking. Trial #3: Eighteen overweight women were divided into three groups of six and trial #2 was repeated with each agent alone vs. placebo using forskolin, yohimbine or aminophylline in separate ointments. Trial #4: Thirty overweight women had 10% aminophylline ointment applied to the thigh five times a week for 6 weeks with diet and walking. Chemistry panel, theophylline level and patch testing were performed. Trial #5: Twelve women had trial #4 repeated with 2% aminophylline cream without a diet or walking. Trial #6: Trial #5 was repeated with 0.5% aminophylline cream. All trials except yohimbine ointment gave significantly more girth loss from the treated thigh (p < 0.05 to p < 0.001). Chemistry panel showed no toxicity. Theophylline was undetectable and patch testing was negative. We conclude that topical fat reduction for women's thighs can be achieved without diet or exercise.

Adipose Tissue↗

PubMed1995

Nutrient intake is modulated by peripheral peptide administration.

Many peptides have been shown to modulate nutrient intake. In most cases, these peptides decrease food intake, but in a few cases they have been demonstrated to stimulate feeding. Infusion of insulin peripherally will decrease food intake unless hypoglycemia occurs where the reduced glucose is a stimulus to feeding. Other pancreatic hormones including glucagon, amylin, pancreatic polypeptide, and enterostatin reduce food intake. Of the gastrointestinal hormones, cholecystokinin has been the most widely studied and reduces food intake in a number of species, including human beings. Gastrin-releasing peptide and its relative bombesin have been shown to decrease food intake in experimental animals and man. Somatostatin reduces food intake in experimental animals, but no clinical studies are available. Four pituitary peptides also modify food intake. Vasopressin decreases feeding. In contrast, injections of desacetyl melanocyte stimulating hormone (dMSH), growth hormone, and prolactin are associated with increased food intake. Finally, there are a group of miscellaneous peptides which modulate feeding. beta-casomorphin, a hepta peptide produced during the hydrolysis of casein, stimulates food intake in experimental animals. In contrast, the other peptides in this group including calcitonin, apolipoprotein A-IV, the cyclized form of histidyl-proline, several cytokines, and thyrotropin-releasing hormone decrease food intake. Many of these peptides act on gastrointestinal or hepatic receptors which relay messages to the brain via the afferent vagus nerve. As a group they provide a number of leads for potential drug development.

Animals↗

PubMed1995

Association of body mass with dietary restraint and disinhibition.

The relationship of disinhibition and dietary restraint with body mass was studied in a sample of 293 women. Results suggested that higher body mass was associated with an interaction of disinhibition and dietary restraint. The association of disinhibition with higher body mass was moderated by increased dietary restraint. Symptoms of an eating disorder were more strongly associated with disinhibition than with dietary restraint. These results suggest that dieting may moderate the increased body mass associated with overeating. Psychological and eating problems associated with dietary restraint were found to be of less significance than those associated with disinhibition.

Adolescent↗

PubMed1995

Peripheral 3-hydroxybutyrate and food intake in a model of dietary-fat induced obesity: effect of vagotomy.

We have examined the effect of peripheral 3-hydroxybutyrate injections on food intake and the contribution of the vagus nerve in the resistance to dietary fat-induced obesity in a rodent model. S 5B/Pl rats, which are resistant to dietary-fat induced obesity, and Osborne-Mendel rats, which are sensitive, were adapted to reverse light cycle. Food intake was measured for 24 h following the injection of 3-hydroxybutyrate, lactate, or glycerol (all 5 mMol/kg0.75, SC) at the onset of dark. Three-hydroxybutyrate reduced food intake (p < 0.0001) in S 5B/Pl rats only. Lactate reduced food intake slightly (p < 0.009) in both strains and glycerol had no effect on food intake. In a second experiment, S 5B/Pl and Osborne-Mendel rats were adapted to a high-fat diet and were then subjected to either selective hepatic vagotomy or sham operation. Vagotomy had no effect on weight gain of Osborne-Mendel rats but allowed weight gain in S 5B/Pl rats (p < 0.0001). Even in vagotomized S 5B/Pl rats, however, blood 3-hydroxybutyrate levels were inversely associated (r = -0.50) with food intake. These data suggest that the hepatic vagus nerve may contribute to the resistance of S 5B/Pl rats to dietary-fat induced obesity, but the data do not rule out a strictly central role for the regulation of food intake by 3-hydroxybutyrate in this strain.

3-Hydroxybutyric Acid↗

PubMed1995

Bombesin-induced hypothermia in rats tested at normal ambient temperatures: contribution of the sympathetic nervous system.

Rats infused centrally with bombesin become hypothermic at normal ambient temperatures when acutely deprived of food, but not while allowed unrestrained access to food. Ad lib-fed rats, tested at normal ambient temperatures, become hypothermic after receiving intracerebroventricular (ICV) bombesin when they have ventromedial hypothalamic lesions or when administered insulin or 2-deoxy-D-glucose peripherally. All of these conditions have been linked to reductions of sympathetic nervous system activity to brown adipose tissue (BAT), a major thermogenic mechanism of many homeotherms. A between group design was used to examine the effects of ICV bombesin infusions on the response to peripheral injections of a) the sympathetic ganglionic blocker chlorisondamine (2.5 mg/kg, IP) in ad lib-fed rats, b) the nonspecific beta-agonist isoproterenol (30 mg/kg, IP) in food-deprived rats, and c) the combination of isoproterenol and chlorisondamine in ad lib-fed rats. Ad lib-fed rats receiving ICV bombesin (100 ng/5 microliters), in combination with peripheral chlorisondamine injection, became hypothermic 60 min postbombesin administration (-2.84 +/- 0.33 degrees C), while ad lib-fed rats receiving ICV bombesin infusion and peripheral injections of saline did not (-0.08 +/- 0.37 degrees C). Isoproterenol blocked hyperthermia in ad lib-fed rats injected with chlorisondamine and ICV bombesin. Food-derived rats receiving ICV bombesin infusion and peripheral saline injection exhibited hypothermia 60 min postbombesin administration (-2.51 +/- 0.29 degrees C). Peripheral injections of isoproterenol prevented bombesin-induced hypothermia in food-deprived rats. These data suggest that bombesin induces hypothermia at normal ambient temperatures when the sympathetic nervous system drive to BAT cannot be (or is not) activated.

Adipose Tissue, Brown↗

PubMed1995

Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin-dependent diabetes mellitus.

BACKGROUND: Acarbose delays release of glucose from complex carbohydrates and disaccharides by inhibiting intestinal alpha-glucosidases, thereby attenuating postprandial increments in blood glucose and insulin. This multicenter, double-blind, placebo-controlled study compared the efficacy and safety of diet alone, acarbose, tolbutamide, and acarbose-plus-tolbutamide in non-insulin-dependent diabetes mellitus (NIDDM) patients. PATIENTS AND METHODS: A total of 290 patients with NIDDM and fasting plasma glucose levels of at least 140 mg/dL were randomized to receive treatment TID with acarbose 200 mg, tolbutamide 250 to 1,000 mg, a combination of both drugs, or placebo. A 6-week run-in period was followed by double-blind treatment for 24 weeks, then a 6-week follow-up period. RESULTS: All active treatments were superior (P < 0.05) to placebo in reducing postprandial hyperglycemia and HbA1c levels. The ranking in order of efficacy was: acarbose-plus-tolbutamide, tolbutamide, acarbose, and placebo. The postprandial reductions in glucose were approximately 85 mg/dL for acarbose-plus-tolbutamide, 71 mg/dL for tolbutamide, 56 mg/dL for acarbose, and 13 mg/dL for placebo. Tolbutamide was associated with increases in body weight and postprandial insulin levels when taken alone, but these were ameliorated when tolbutamide was taken in combination with acarbose. Acarbose alone or in combination with tolbutamide caused significantly more gastrointestinal adverse events (mainly flatulence and soft stools or diarrhea) than tolbutamide or placebo, but these were generally well tolerated. Clinically significant elevations in hepatic transaminase levels occurred in 3 patients in the acarbose group and 2 in the acarbose-plus-tolbutamide group. Transaminase levels returned to normal when therapy was discontinued. CONCLUSIONS: Acarbose was effective and well tolerated in the treatment of NIDDM. Control of glycemia was significantly better with acarbose compared with diet alone. Acarbose-plus-tolbutamide was superior to tolbutamide alone.

Acarbose↗

PubMed1995

Regulation of beta 3-adrenergic receptor mRNA by sympathetic nerves and glucocorticoids in BAT of Zucker obese rats.

Impaired brown adipose tissue (BAT) thermogenesis in the genetically obese Zucker fatty (fa/fa) rat is restored to normal by adrenalectomy. We investigated the role of the sympathetic nervous system in modulating the effects of adrenalectomy by studying beta3-adrenergic receptor (AR) and uncoupling protein (UCP) mRNA levels in unilaterally sympathectomized interscapular BAT of lean and obese rats. UCP mRNA levels were increased by adrenalectomy. Sympathetic denervation prevented this adrenalectomy-induced increase in lean rats but not in obese rats. beta 3-AR mRNA was decreased in BAT of obese rats. Adrenalectomy decreased and denervation increased beta 3-AR mRNA in lean rats but the opposite response was observed to both of these manipulations in obese rats. beta 3-AR mRNA and UCP mRNA were negatively correlated in lean rats but positively correlated in obese rats. Norepinephrine increased UCP mRNA levels in denervated BAT of both lean and obese rats and decreased beta 3-AR mRNA in lean rats but not obese rats. These data suggest that the regulation of the beta 3-AR gene in response to sympathetic stimuli and glucocorticoids is abnormal in the obese rat.

Adipose Tissue, Brown↗

PubMed1995

Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases abdominal fat in obese, older men.

OBJECTIVE: To compare the effects of testosterone enanthate (TE), anabolic steroid (AS) or placebo (PL) on regional fat distribution and health risk factors in obese middle-aged men undergoing weight loss by dietary means. DESIGN: Randomized, double-blind, placebo-controlled clinical trial, carried out for 9 months with primary assessments at 3 month intervals. Due to adverse blood lipid changes, the AS group was switched from oral oxandrolone (ASOX) to parenteral nandrolone decaoate (ASND) after the 3 month assessment point. SUBJECTS: Thirty healthy, obese men, aged 40-60 years, with serum testosterone (T) levels in the low-normal range (2-5 ng/mL). MAIN OUTCOME MEASURES: Abdominal fat distribution and thigh muscle volume by CT scan, body composition by dual energy X-ray absorptiometry (DEXA), insulin sensitivity by the Minimal Model method, blood lipids, blood chemistry, blood pressure, thyroid hormones and urological parameters. RESULTS: After 3 months, there was a significantly greater decrease in subcutaneous (SQ) abdominal fat in the ASOX group compared to the TE and PL groups although body weight changes did not differ by treatment group. There was also a tendency for the ASOX group to exhibit greater losses in visceral fat, and the absolute level of visceral fat in this group was significantly lower at 3 months than in the TE and PL groups. There were significant main effects of treatment at 3 months on serum T and free T (increased in the TE group and decreased in the ASOX group) and on thyroid hormone parameters (T4 and T3 resin uptake significantly decreased in the ASOX group compared with the other two groups). There was a significant decrease in HDL-C, and increase in LDL-C in the ASOX group, which led to their being switched to the parenteral nandrolone decanoate (ASND) after 3 months. ASND had opposite effects on visceral fat from ASOX, producing a significant increase from 3 to 9 months while continuing to decrease SQ abdominal fat. ASND treatment also decreased thigh muscle area, while ASOX treatment increased high muscle. ASND reversed the effects of ASOX on lipoproteins and thyroid hormones. The previously reported effect of T to decrease visceral fat was not observed, in fact, visceral fat in the TE group increased slightly from 3 to 9 months, although SQ fat continued to decrease. Neither TE nor AS treatment resulted in any change in urologic parameters. CONCLUSIONS: Oral oxandrolone decreased SQ abdominal fat more than TE or weight loss alone and also tended to produce favorable changes in visceral fat. TE and ASND injections given every 2 weeks had similar effects to weight loss alone on regional body fat. Most of the beneficial effects observed on metabolic and cardiovascular risk factors were due to weight loss per se. These results suggest that SQ and visceral abdominal fat can be independently modulated by androgens and that at least some anabolic steroids are capable of influencing abdominal fat.

Adipose Tissue↗

PubMed1994

A case for drug treatment of obesity.

Several brain receptor systems can modulate food intake. Thus, in a new strategy against obesity, the patient takes submaximal doses of two drugs that act by differing mechanisms.

Adrenergic beta-Agonists↗

PubMed1994

Commentary on classics in obesity. 1. Quetelet: quantitative medicine.

Explore the source record for details and available documents.

Body Height↗