Alina Gavrila

Anatomical Localization, Gene Expression Profiling, and Functional Characterization of Adult Human Neck Brown Fat

The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1). BAT was once thought to have a functional role in rodents and human infants only, but it has been recently shown that in response to mild cold exposure, adult human BAT consumes more glucose per gram than any other tissue. In addition to this nonshivering thermogenesis, human BAT may also combat weight gain by becoming more active in the setting of increased whole-body energy intake. This phenomenon of BAT-mediated diet-induced thermogenesis has been observed in rodents and suggests that activation of human BAT could be used as a safe treatment for obesity and metabolic dysregulation. In this study, we isolated anatomically defined neck fat from adult human volunteers and compared its gene expression, differentiation capacity and basal oxygen consumption to different mouse adipose depots. Although the properties of human neck fat vary substantially between individuals, some human samples share many similarities with classical, also called constitutive, rodent BAT.

Human Immunodeficiency Virus Type 1-Related Lipoatrophy and Lipohypertrophy Are Associated with Serum Concentrations of Leptin

The relationship between the adipocyte-derived hormone leptin, insulin resistance, and fat redistribution in patients with human immunodeficiency virus (HIV) infection has not been established. We classified a cohort of HIV type 1 (HIV-1)-infected patients with >or=6 months of antiretroviral exposure as having no lipodystrophy (51 patients [43% of the cohort]), lipoatrophy (23 patients [19% of the cohort]), mixed lipodystrophy (29 patients [24% of the cohort]), or lipohypertrophy (17 patients [14% of the cohort]), on the basis of physical examination, anthropometric measurements, and the findings of dual-emission x-ray absorptiometry and computed tomography. Measurements of insulin resistance were higher for patients with each category of lipodystrophy, compared with those observed for patients with no lipodystrophy (P<.001). Mean leptin levels (+/- standard deviation) were lowest in patients with lipoatrophy (1.76+/-1.20 ng/mL), highest in patients with lipohypertrophy (9.10+/-6.86 ng/mL), and significantly different from those in patients without lipodystrophy (3.14+/-2.30 ng/mL; both P<.01). In this cohort of antiretroviral-experienced HIV-infected patients, a low serum level of leptin was independently associated with insulin resistance in patients with lipoatrophy, after controlling for total and regional body fat.

Improvement in Highly Active Antiretroviral Therapy—Induced Metabolic Syndrome by Treatment with Pioglitazone but Not with Fenofibrate: A 2 × 2 Factorial, Randomized, Double-Blinded, Placebo-Controlled Trial

We designed a 2 x 2 factorial, randomized, double-blinded, placebo-controlled trial to evaluate the effects of treatment with pioglitazone and/or fenofibrate in patients with highly active antiretroviral therapy (HAART)-induced metabolic syndrome. We found that the administration of pioglitazone, but not fenofibrate, improved insulin resistance, blood pressure, and lipid profile over a 12-month period.

Exercise and Vitamin E Intake Are Independently Associated with Metabolic Abnormalities in Human Immunodeficiency Virus—Positive Subjects: A Cross-Sectional Study

We investigated the relationship among habitual exercise, diet, and the presence of metabolic abnormalities (body fat redistribution, dyslipidemia, and insulin resistance) in a cross-sectional study of 120 human immunodeficiency virus (HIV)-infected subjects with use of bivariate and multivariate regression-analysis models. Total and aerobic exercise were significantly and negatively associated with fasting plasma triglyceride levels in the entire sample and in the fat redistribution group. Inverse associations between total or aerobic exercise and insulin resistance were suggestive but did not achieve statistical significance. Diastolic blood pressure was significantly and inversely associated with supplemental or total but not habitual dietary intake of vitamin E. In conclusion, exercise and vitamin E intake were independently and negatively associated with several phenotypic manifestations of HIV-associated metabolic syndrome, whereas other macro- or micronutrients did not have comparable significance.

Leptin, Adiponectin, Resistin, Ghrelin

In parallel with the continuous increase in the prevalence of obesity, intense research activity has been recently conducted to better understand energy balance and the regulation of metabolism and body weight. This review discusses the potential role of four recently discovered molecules involved in metabolism and energy homeostasis: leptin, adiponectin, resistin, and ghrelin.

Adiponectin and the Cardiovascular System

Adiponectin, a recently discovered protein produced exclusively by adipocytes, is thought to be a possible mediator between obesity, insulin resistance, and cardiovascular disease (CVD). Although its function is not entirely known, body fat distribution, insulin, sex hormones, tumor necrosis factor (TNF)-α, and peroxisome proliferator-activated receptor (PPAR)-α may contribute to its regulation. Along with being associated with cardiovascular risk factors such as diabetes and dyslipidemia, deficiency in adiponectin may also directly compromise endothelial action and promote atherosclerosis.