Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats. Am J Physiol Endocrinol Metab 280: E130-E142, 2001.-In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulinstimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic ␤-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.ob gene product; high-fat diet; glucose tolerance; glucose uptake and transport; GLUT-4 protein LEPTIN, THE PRODUCT of the ob gene (62), has received a great deal of attention since its discovery in 1994, due to the ability of this 16-kDa protein hormone to reduce visceral adipose deposition (21,37). This biological activity is important from a public health perspective, as increases in visceral fat have been associated with "insulin resistance syndrome" or Syndrome X (39). Attenuation of insulin resistance will decrease the incidence of metabolic abnormalities such as hypertriglyceridemia, reduced high-density lipoproteins, elevated apolipoprotein B levels, and hypertension. Furthermore, reduced visceral fat deposition may also prevent the development of non-insulin-dependent diabetes (17).It is believed that leptin exerts its primary effect by acting on receptors in the hypothalamus, possibly via inhibition of neuropeptide Y release (47). However, leptin receptor isoforms are expressed in tissues other than the hypothalamus (12, 29, 51), and insulin action (e.g., phosphatidylinositol 3-kinase activity, skeletal muscle glucose uptake and transport) is improved in these tissues after leptin treatment (3,56,57,60). Improvements in insulin-stimulated glucose disposal after chronic leptin administration were initially demonstrated by Barzilai et al. (3) and Sivitz et al. (44). Barzilai et al. (3) reported that 8 days of leptin treatment increased whole body glucose uptake in SpragueDawley rats as assessed by the euglycemic clamp technique. In an extension to these findings, we (60) found that 14...

Research Methods and Procedures:The national representative sample of the Mexican urban adult population included 8462 women and 5929 men aged 20 to 69 years from 417 towns of Ͼ2500 people. Body mass index (BMI), calculated from measured weight and height, was classified using the World Health Organization categories of underweight (BMI Ͻ 18.5 kg/m 2 ), normal weight (BMI 18.5 to 24.9 kg/m 2 ), pre-obesity (PreOB ϭ BMI 25 to 29.9 kg/m 2 ) and obesity (OB ϭ BMI 30ϩ kg/m 2 ). Estimates for Mexican Americans were calculated from U.S. survey data. Results: Overall, 38% of the Mexican urban adult population were classified as pre-obese and 21% as obese. Men had a higher prevalence of pre-obesity than women did at all ages, but women had higher values of obesity. Both preobesity and obesity increased with age up to the age range brackets of 40 to 49 or 50 to 59 years for both men and women. Both pre-obesity and obesity prevalence estimates were remarkably similar to data for Mexican Americans from 1982 through 1984. Comparison with other large surveys showed that countries differed more in the prevalence of obesity than of pre-obesity, leading to differences in the PreOB/OB ratio, and that countries also differed in the gender ratio (female/male) for both pre-obesity and obesity. Discussion: Pre-obesity and obesity were high in our population and increased with age. Our approach of characterizing large surveys by PreOB/OB and gender ratios appeared promising.

The Maya and mestizo population of Yucatan showed a high prevalence of obesity and abnormal waist circumference not accompanied by a comparable higher hypertension frequency. This finding requires further confirmation.

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