Wiley

Recent progress in the molecular pharmacology of 5‐HT receptors and the development of selective ligands for various 5‐HT receptor subtypes has advanced our understanding of the role of 5‐HT mechanisms in the control of food intake and body weight The most intensively investigated 5‐HT receptor subtypes have been the 5‐HT_1A receptor, the 5‐HT_1B receptor andthe5‐HT_2C receptor. The overall pattern of results to date suggests that selective 5‐HT_2C agonists may be novel anorectic drugs and prove useful in the treatment of obesity. However, a number of issues remain unresolved, particularly regarding potential side‐effects, as the 5‐HT_2C receptor agonist mCPP has been reported to induce anxiety and nausea in humans, actions that would clearly limit its therapeutic utility. In addition, the possible role of recently cloned 5‐HT receptor subtypes such as 5‐ht₅,5‐ht₆ and 5‐ht₇ remains unexplored and the development of selective ligands for these sites has the potential to lead to new treatments for obesity.

Objectives: The activity of adipose 11β‐hydroxysteroid dehydrogenase (11β‐HSD) 1 is increased in obese subjects, and animal data suggest that increased cortisol formation in adipose tissue contributes to the development of the metabolic syndrome. The aim of this study was to determine whether up‐regulation of human adipose 11β‐HSD1 in obesity can also be found at the gene expression level.

Research Methods and Procedures: 11β‐HSD gene expression in subcutaneous adipose tissue biopsies of 70 postmenopausal women was studied by real‐time reverse‐transcription polymerase chain reaction. The influence of weight reduction and in vitro effects of several modulators of adipocyte gene expression on 11β‐HSD genes in human adipocytes were also studied.

Results: The 11β‐HSD1 gene was highly expressed in human adipose tissue. 11β‐HSD2 mRNA was also detectable at lower levels. Adipose 11β‐HSD1 gene expression was increased by two‐fold and was positively correlated with waist circumference and homeostasis model assessment index of insulin resistance. 11β‐HSD2 gene expression was reduced by half in obese women. Weight reduction did not change gene expression levels of 11β‐HSD1 or 11β‐HSD2. Cortisol increased 11β‐HSD1 gene expression in isolated human adipocytes in vitro, whereas estradiol, triiodothyronine, angiotensin II, and pioglitazone had no influence.

Discussion: Our data suggest that increased expression of the 11β‐HSD1 gene is associated with metabolic abnormalities in obese women and that increased expression of this gene may contribute to the previously reported increased local conversion of cortisone to cortisol in adipose tissue of obese individuals.

Objective: The longitudinal relationship between the consumption of energy‐dense snack (EDS) foods and relative weight change during adolescence is uncertain. Using data from the Massachusetts Institute of Technology Growth and Development Study, the current analysis was undertaken to examine the longitudinal relationship of EDS food intake with relative weight status and percentage body fat and to examine how EDS food consumption is related to television viewing.

Research Methods and Procedures: One hundred ninety‐six nonobese premenarcheal girls 8 to 12 years old were enrolled between 1990 and 1993 and followed until 4 years after menarche. At each annual follow‐up visit, data were collected on percentage body fat (%BF), BMI z score, and dietary intake. Categories of EDS foods considered were baked goods, ice cream, chips, sugar‐sweetened soda, and candy.

Results: At study entry, girls had a mean ± SD BMI z score of −0.27 ± 0.89, consumed 2.3 ± 1.7 servings of EDS foods per day, and consumed 15.7 ± 8.1% of daily calories from EDS foods. Linear mixed effects modeling indicated no relationship between BMI z score or %BF and total EDS food consumption. Soda was the only EDS food that was significantly related to BMI z score over the 10‐year study period, but it was not related to %BF. In addition, a significant, positive relationship was observed between EDS food consumption and television viewing.

Discussion: In this cohort of initially nonobese girls, overall EDS food consumption does not seem to influence weight status or fatness change over the adolescent period.

Trong nghiên cứu này, khi được sử dụng như một chất bổ sung cho chế độ ăn thấp năng lượng, tác nhân giao cảm ephedrine, kết hợp với các methylxanthine như caffeine, cải thiện khả năng giảm mỡ bằng hai cơ chế: ức chế sự thèm ăn trung ương và kích thích chi tiêu năng lượng ngoại biên thông qua quá trình oxy hóa mỡ. Sự giảm cân trung bình được ghi nhận là 16,6 kg sau 6 tháng khi E+C được sử dụng như một bổ sung cho chế độ ăn kiêng hiệu quả, cao hơn 3,4 kg so với nhóm placebo. Việc điều trị thêm 24 tuần với E+C đã ngăn chặn sự tái phát. Trong những tuần đầu của điều trị, E+C đã bù đắp cho hiệu ứng hạ huyết áp do việc giảm năng lượng và giảm cân, nhưng hiệu ứng này tạm thời, và sau 8 tuần, huyết áp không khác biệt so với nhóm placebo. E+C không có tác động tiêu cực đến chuyển hóa glucose và lipid, nhưng đã được chứng minh là ngăn chặn sự giảm xuống của HDL-cholesterol do giảm cân. Trong một thử nghiệm so sánh, sự giảm cân do E+C đạt mức tương tự như dexfenfluramine. Cần tiếp tục nghiên cứu về các tác nhân giao cảm và methylxanthine để xác định các kết hợp có hiệu quả và an toàn hơn. Hơn nữa, cần có thêm các thử nghiệm dài hạn và nghiên cứu trên nam giới.

Obesity causes serious medical complications and impairs quality of life. Moreover, in older persons, obesity can exacerbate the age‐related decline in physical function and lead to frailty. However, appropriate treatment for obesity in older persons is controversial because of the reduction in relative health risks associated with increasing body mass index and the concern that weight loss could have potential harmful effects in the older population. This joint position statement from the American Society for Nutrition and NAASO, The Obesity Society reviews the clinical issues related to obesity in older persons and provides health professionals with appropriate weight‐management guidelines for obese older patients. The current data show that weight‐loss therapy improves physical function, quality of life, and the medical complications associated with obesity in older persons. Therefore, weight‐loss therapy that minimizes muscle and bone losses is recommended for older persons who are obese and who have functional impairments or medical complications that can benefit from weight loss.

In developed countries, there is a general increase in body weight and body mass index (BMI) with age, until ∼60 years of age, when body weight and BMI begin to decline. The proportion of intra‐abdominal fat, which is related to increased morbidity and mortality, progressively increases with age. There is also a progressive decline in energy intake and daily total energy expenditure (165 kcal/decade in men and 103 kcal/decade in women in developed countries), which is primarily due to a decrease in physical activity, and to a lesser extent, a decrease in basal metabolic rate. The decrease in physical activity is more pronounced in those with chronic disabilities and diseases. The BMI–mortality curves have been reported to move upward (greater overall mortality), become flatter (less effect of BMI on mortality), and in some cases shift to the right (minimum mortality occurs at a higher BMI), for a variety of possible reasons. Weight loss in the elderly has been reported to increase, decrease, or not alter mortality, but the studies are confounded by numerous methodological problems. It has been argued that there may be little benefit in encouraging weight loss in extreme old age (short life expectancy), especially when there are no obesity‐related complications or biochemical risk factors and when strong resistance and distress arise from changes in lifelong habits of eating and exercise. In contrast, weight loss in the elderly can reduce morbidity from arthritis, diabetes and other conditions, reduce cardiovascular risk factors, and improve well‐being. BMI also predicts morbidity in those without disease. Furthermore, increased physical activity in the elderly, which is an important component of weight management, can produce beneficial effects on muscle strength, endurance, and well‐being.

This article reviews information on discriminatory attitudes and behaviors against obese individuals, integrates this to show whether systematic discrimination occurs and why, and discusses needed work in the field. Clear and consistent stigmatization, and in some cases discrimination, can be documented in three important areas of living: employment, education, and health care. Among the findings are that 28% of teachers in one study said that becoming obese is the worst thing that can happen to a person; 24% of nurses said that they are “repulsed” by obese persons; and, controlling for income and grades, parents provide less college support for their overweight than for their thin children. There are also suggestions but not yet documentation of discrimination occurring in adoption proceedings, jury selection, housing, and other areas. Given the vast numbers of people potentially affected, it is important to consider the research‐related, educational, and social policy implications of these findings.

Objective: To evaluate interactions among leptin, adiponectin, resistin, ghrelin, and proinflammatory cytokines [tumor necrosis factor receptors (TNFRs), interleukin‐6 (IL‐6)] in nonmorbid and morbid obesity.

Research Methods and Procedures: We measured these hormones by immunoenzyme or radiometric assays in 117 nonmorbid and 57 morbidly obese patients, and in a subgroup of 34 morbidly obese patients before and 6 months after gastric bypass surgery. Insulin resistance by homeostasis model assessment, lipid profile, and anthropometrical measurements were also performed in all patients.

Results: Average plasma lipids in morbidly obese patients were elevated. IL‐6, leptin, adiponectin, and resistin were increased and ghrelin was decreased in morbidly obese compared with nonmorbidly obese subjects. After adjusting for age, gender, and BMI in nonmorbidly obese, adiponectin was positively associated with HDLc and gender and negatively with weight (β = −0.38, p < 0.001). Leptin and resistin correlated positively with soluble tumor necrosis factor receptor (sTNFR) 1 (β = 0.24, p = 0.01 and β = 0.28, p = 0.007). In the morbidly obese patients, resistin and ghrelin were positively associated with sTNFR2 (β = 0.39, p = 0.008 and β = 0.39, p = 0.01). In the surgically treated morbidly obese group, body weight decreased significantly and was best predicted by resistin concentrations before surgery (β = 0.45, p = 0.024). Plasma lipids, insulin resistance, leptin, sTNFR1, and IL‐6 decreased and adiponectin and ghrelin increased significantly. Insulin resistance improved after weight loss and correlated with high adiponectin levels.

Discussion: TNFα receptors were involved in the regulatory endocrine system of body adiposity independently of leptin and resistin axis in nonmorbidly obese patients. Our results suggest coordinated roles of adiponectin, resistin, and ghrelin in the modulation of the obesity proinflammatory environment and that resistin levels before surgery treatment are predictive of the extent of weight loss after bypass surgery.

Objective: Treatment of male rodents with estradiol (E₂) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin‐concentrating hormone (MCH) and the appetite‐inhibiting, fat‐derived hormone leptin in mediating E₂‐induced anorexia.

Research Methods and Procedures: We studied the effect of E₂ treatment (implantation of either E₂ pellet or matching placebo) in male C57Bl/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin‐deficient ob/ob mice). We also studied the effect of E₂ treatment in the context of high‐fat diet.

Results: We confirmed E₂ dose‐dependent anorexia in male wild type mice fed a normal chow diet. E₂ treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E₂‐implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E₂‐induced hypophagia, we performed E₂ pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E₂‐induced anorexia. E₂‐implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E₂‐induced anorexia. High‐fat diet significantly exacerbated the effect of E₂ treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week.

Discussion: The anorectic effects of E₂ were independent of MCH and leptin. Our results suggested that E₂ may have effects on nutrient preferences.