Obesity: Planet Earth

Tchernof A, Poehlman ET, Després JP. · Department of Medicine, University of Vermont, Burlington, VT 05401, USA. · Diabetes Metab. · Pubmed #10705099 links to  free full text

Abstract: Endocrine changes resulting from the menopause transition dramatically modify women's hormonal milieu. The consequences of these changes not only lead to cessation of reproduction and accompanying symptoms in women, but also dramatically impact long-term health. Loss of estrogen has been associated with the development of cardiovascular disease. Central distribution and accumulation of adipose tissue, and the concomitant insulin resistant dyslipidemic state have emerged as important components of a cluster of metabolic abnormalities that are strongly related to coronary heart disease. Thus, estrogen deficiency may affect cardiovascular disease risk by mediating changes in body fat distribution. This article is an update of the literature in the area of menopause, hormone replacement therapy, and body fat distribution. Cross-sectional studies using anthropometric measurements of abdominal fat distribution most often failed to detect an effect of the menopause transition that was independent of advancing age and degree of obesity. The use of radiologic techniques such as DEXA and computed tomography, however, led to the conclusion that the menopause transition accelerates the selective deposition of intra-abdominal fat. Available longitudinal data also support an increase in central body fatness occurring with menopause. Most intervention trials on hormone replacement therapy and body fat distribution showed that the treatment prevented the increase in central adiposity that was noted in postmenopausal women receiving no treatment or placebo. These results are supported by retrospective studies that showed a lower WHR in hormone users vs non-users. Mechanisms potentially explaining the menopause-related acceleration in abdominal fat accumulation include changes in regional adipose tissue metabolism in the face of a positive energy imbalance. As some inconsistencies were found among studies, further investigations using longitudinal and intervention designs, as well as more precise methodologies to measure body fat distribution, are needed to clearly establish the effects of menopause and hormone replacement on abdominal body fat distribution and the concomitant increase in cardiovascular disease risk.

Stumvoll M, Wahl HG, Jacob S, Rettig A, Machicao F, Häring H. · Department of Endocrinology and Metabolism, Eberhard-Karls-Universität, D-72076 Tübingen, Germany. · J Lipid Res. · Pubmed #11714847 links to  free full text

Abstract: Free fatty acids released during triglyceride lipolysis play an important role in obesity-associated insulin resistance of glucose disposal. Individual sensitivity of lipolysis to the suppressive effect of insulin varies greatly among healthy subjects. It is possible that genetic factors contribute to this variation. Among the many proteins involved in the regulation of lipolysis, hormone-sensitive lipase (HSL) represents a prime candidate for genetic variants contributing to the biological variation of insulin sensitivity of lipolysis. We determined the insulin sensitivity of lipolysis (suppression of isotopically [primed-continuous infusion of d5 glycerol] measured glycerol rate of appearance) and of glucose disposal, using a three-step (n = 20) or standard (n = 53) hyperinsulinemic euglycemic clamp in 73 healthy, unrelated subjects. To assess the possible role of genetic polymorphisms, we directly sequenced the coding region of the HSL gene and the noncoding exon B from these subjects. We identified two silent mutations and three amino acid polymorphisms: Arg262Met (prevalence, 5%), Glu620Asp (prevalence, 31%) and Ser681Ile (prevalence, 22%). The latter two are located in the regulatory domain of HSL but neither had a significant impact on insulin sensitivity of lipolysis or glucose disposal (with and without adjustment for obesity and age as covariates; all P values > 0.20). We conclude that a number of genetic polymorphisms in HSL exist, some of which are highly prevalent. Neither of the polymorphisms we identified in the coding region, however, contributed measurably to the biological variation of insulin sensitivity in our lean, healthy population.

Poehlman ET. · Department of Medicine, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA. · Acta Obstet Gynecol Scand. · Pubmed #12190834 No free full text.

Abstract: OBJECTIVES: The effects of menopause transition on metabolic and cardiovascular disease risk in women are unclear. It is unknown whether estrogen deficiency, aging, or a combination of both factors are independent contributors to a worsening health profile in women. We considered the effects of menopause transition and hormone replacement therapy on body composition, regional body fat, energy expenditure, and insulin sensitivity. METHODS: A brief review of current literature that has considered the role of menopause transition and hormone replacement therapy on body composition, energy expenditure, and insulin sensitivity with an emphasis on longitudinal investigations. RESULTS: Preliminary evidence suggests that natural menopause is associated with reduced energy expenditure during rest and physical activity, an accelerated loss of fat-free mass, and increased central adiposity and fasting insulin levels. Hormone replacement therapy has been shown to attenuate these changes. Longitudinal and longer intervention studies are needed to confirm these initial findings. CONCLUSIONS: Menopause transition may represent a risky period in a woman's life, 'triggering' adverse metabolic and cardiovascular processes that predispose women to a greater incidence of obesity-related comorbidities. Dietary, exercise, and hormonal interventions specifically targeted at premenopausal women may help mitigate the worsening cardiovascular and metabolic risk profile associated with menopause.

Komazawa N, Matsuda M, Kondoh G, Mizunoya W, Iwaki M, Takagi T, Sumikawa Y, Inoue K, Suzuki A, Mak TW, Nakano T, Fushiki T, Takeda J, Shimomura I. · Department of Social and Environmental Medicine, Graduate School of Frontier Bioscience, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan. · Nat Med. · Pubmed #15489860 No free full text.

Abstract: Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enhanced insulin sensitivity with induced phosphorylation of Akt in adipose tissue. AdipoPten-KO mice also showed marked hyperthermia and increased energy expenditure with induced mitochondriagenesis in adipose tissue, associated with marked reduction of p53, inactivation of Rb, phosphorylation of cyclic AMP response element binding protein (CREB) and increased expression of Ppargc1a, the gene that encodes peroxisome proliferative activated receptor gamma coactivator 1 alpha. Physiologically, adipose Pten mRNA decreased with exposure to cold and increased with obesity, which were linked to the mRNA alterations of mitochondriagenesis. Our results suggest that altered expression of adipose Pten could regulate insulin sensitivity and energy expenditure. Suppression of adipose Pten may become a beneficial strategy to treat type 2 diabetes and obesity.

Accili D, Valenti L. · No affiliation provided · Nat Med. · Pubmed #15516912 No free full text.

This publication has no abstract.

Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. · Department of Medicine and Pathophysiology, Graduate School of Medicine, and Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. · Science. · Pubmed #15604363 links to  free full text

Abstract: Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.

Sjöstrand M, Gudbjörnsdottir S, Strindberg L, Lönnroth P. · Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, S-41345 Göteborg, Sweden. · Diabetes. · Pubmed #15616023 links to  free full text

Abstract: Obese subjects exhibit a delay in insulin action and delivery of insulin to muscle interstitial fluid during glucose/insulin infusion. The aim of the present study was to follow the distribution of insulin to skeletal muscle after an oral glucose load in obese subjects. We conducted an oral glucose tolerance test (OGTT) in 10 lean and 10 obese subjects (BMI 23 +/- 0.6 vs. 33 +/- 1.2 kg/m(2); P < 0.001). Insulin measurements in muscle interstitial fluid were combined with forearm arteriovenous catheterization and blood flow measurements. In the obese group, interstitial insulin was significantly (35-55%) lower than plasma insulin (P < 0.05) during the 1st h after the OGTT, whereas in lean subjects, no significant difference was found between interstitial and plasma insulin levels during the same time period. The permeability surface area product for glucose, representing capillary recruitment, increased in the lean group (P < 0.05) but not in the obese group (NS). Obese subjects had a significantly higher plasma insulin level at 90-120 min after oral glucose (398 +/- 57 vs. 224 +/- 37 pmol/l in control subjects; P < 0.05). The significant gradient between plasma insulin and muscle interstitial insulin during the first hour after OGTT suggests a slow delivery of insulin in obese subjects. The hindered transcapillary transport of insulin may be attributable to a defect in insulin-mediated capillary recruitment.

Oliveira AC, Oliveira AM, Adan LF, Oliveira NF, Silva AM, Ladeia AM. · Bahian School of Medicine and Public Health, Science Development Foundation of Bahia, Salvador, Bahia, Brazil. · Obesity (Silver Spring). · Pubmed #18356840 No free full text.

Abstract: OBJECTIVE: Metabolic syndrome (MS) is on the rise in youth. As high-sensitivity C-reactive protein (hs-CRP) is associated with cardiovascular/metabolic disorders, we evaluated the association between MS and its components and hs-CRP in a sample of Brazilian overweight and obese youth. METHODS AND PROCEDURES: A total of 407 students (229 girls, 273 with excessive weight, 11.3+/-3.2 years) were evaluated. Measurement included BMI, waist circumference (WC), blood pressure, lipids, insulin, and hs-CRP. Excessive weight was defined using BMI z -score; MS by the modified National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: Subjects were classified into two groups: with MS (n=72) and without (n=335). hs-CRP means and medians were higher in MS group (1.41 mg/l vs. 1.06 mg/l, P<0.001; 2.21 mg/l vs. 1.23 mg/l, P<0.001). Associations between hs-CRP quartiles and insulin resistance (IR) (P<0.001), MS (P<0.001), WC (P<0.000), BMI z-score (P<0.001), hypertension (P<0.001), hypertriglyceridemia (P<0.001), and low HDL-c (P=0.023) were significant; adjustment of hs-CRP for BMI z-score eliminated the previous association, except for the number of MS components (nMSc) (P<0.001). Adjusting for homeostasis model assessment method of IR (HOMA-IR) did not eliminate the relation between hs-CRP and MS components. Furthermore, increases in BMI z-score and nMSc were associated with an increased hs-CRP. Excessive weight (odds ratio (OR), 7.9; confidence interval (CI), 4.7-13.4; P=0.000), hypertension (OR, 2.3; CI, 1.3-4.2; P=0.003), and hypertriglyceridemia (OR, 2.3; CI, 1.5-3.7; P<0.001) were independently associated with hs-CRP. DISCUSSION: In youth, hs-CRP is strongly related with MS and its components, and is also determined by the body composition. This association indicates a precocious proinflammatory state.

Mechanick JI, Kushner RF, Sugerman HJ, Gonzalez-Campoy JM, Collazo-Clavell ML, Guven S, Spitz AF, Apovian CM, Livingston EH, Brolin R, Sarwer DB, Anderson WA, Dixon J, Anonymous00003, Anonymous00004, Anonymous00005. · No affiliation provided · Endocr Pract. · Pubmed #18463039 No free full text.

This publication has no abstract.

Mechanick JI, Kushner RF, Sugerman HJ. · Mount Sinai School of Medicine, New York, New York, USA. · Endocr Pract. · Pubmed #18754175 No free full text.

This publication has no abstract.