Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study

BACKGROUND: The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women. METHODS: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis. RESULTS AND DISCUSSION: In multivariate analysis, women who were overweight (BMI > 25 to ≤ 30 kg/m(2)) had a 2-fold increase, and obese women (BMI > 30 kg/m(2)) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI ≤25 kg/m(2)) women. When the models for the different measures of adiposity were assessed by multiple R(2), models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance. CONCLUSION: Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin

Role of Mcpip1 in obesity‐induced hepatic steatosis as determined by myeloid and liver‐specific conditional knockouts

Monocyte chemoattractant protein‐induced protein 1 (MCPIP1, alias Regnase 1) is a negative regulator of inflammation, acting through cleavage of transcripts coding for proinflammatory cytokines and by inhibition of NFκB activity. Moreover, it was demonstrated that MCPIP1 regulates lipid metabolism both in adipose tissue and in hepatocytes. In this study, we investigated the effects of tissue‐specific Mcpip1 deletion on the regulation of hepatic metabolism and development of nonalcoholic fatty liver disease (NAFLD). We used control Mcpip1(fl/fl) mice and animals with deletion of Mcpip1 in myeloid leukocytes (Mcpip1(fl/fl)LysM(Cre)) and in hepatocytes (Mcpip1(fl/fl)Alb(Cre)), which were fed chow or a high‐fat diet (HFD) for 12 weeks. Mcpip1(fl/fl)LysM(Cre) mice fed a chow diet were characterized by a significantly reduced hepatic expression of genes regulating lipid and glucose metabolism, which subsequently resulted in low plasma glucose level and dyslipidemia. These animals also displayed systemic inflammation, demonstrated by increased concentrations of cytokines in the plasma and high Tnfa, Il6, IL1b mRNA levels in the liver and brown adipose tissue (BAT). Proinflammatory leukocyte infiltration into BAT, together with low expression of Ucp1 and Ppargc1a, resulted in hypothermia of 22‐week‐old Mcpip1(fl/fl)LysM(Cre) mice. On the other hand, there were no significant changes in phenotype in Mcpip1(fl/fl)Alb(Cre) mice. Although we detected a reduced hepatic expression of genes regulating glucose metabolism and β‐oxidation in these mice, they remained asymptomatic. Upon feeding with a HFD, Mcpip1(fl/fl)LysM(Cre) mice did not develop obesity, glucose intolerance, nor hepatic steatosis, but were characterized by low plasma glucose level and dyslipidemia, along with proinflammatory phenotype. Mcpip1(fl/fl)Alb(Cre) animals, following a HFD, became hypercholesterolemic, but accumulated lipids in the liver at the same level as Mcpip1(fl/fl) mice, and no changes in the level of soluble factors tested in the plasma were detected. We have demonstrated that Mcpip1 protein plays an important role in the liver homeostasis. Depletion of Mcpip1 in myeloid leukocytes, followed by systemic inflammation, has a more pronounced effect on controlling liver metabolism and homeostasis than the depletion of Mcpip1 in hepatocytes