Journal Article

Sexual Dimorphic Regulation of Body Weight Dynamics and Adipose Tissue Lipolysis

Mahmoodzadeh, Shokoufeh, Böhm, Christian, Spranger, Joachim, Wardat, Sami, Foryst-Ludwig, Anna, Bloch, Mandy, Maurer, Lukas, Wiedmer, Petra, Benz, Verena, Kintscher, Ulrich

2012

Overview

Successful reduction of body weight (BW) is often followed by recidivism to obesity. BW-changes including BW-loss and -regain is associated with marked alterations in energy expenditure (EE) and adipose tissue (AT) metabolism. Since these processes are sex-specifically controlled, we investigated sexual dimorphisms in metabolic processes during BW-dynamics (gain-loss-regain). Obesity was induced in C57BL/6J male (m) and female (f) mice by 15 weeks high-fat diet (HFD) feeding. Subsequently BW was reduced (-20%) by caloric restriction (CR) followed by adaptive feeding, and a regain-phase. Measurement of EE, body composition, blood/organ sampling were performed after each feeding period. Lipolysis was analyzed ex-vivo in gonadal AT. Male mice exhibited accelerated BW-gain compared to females (relative BW-gain m:140.5±3.2%; f:103.7±6.5%; p<0.001). In consonance, lean mass-specific EE was significantly higher in females compared to males during BW-gain. Under CR female mice reached their target-BW significantly faster than male mice (m:12.2 days; f:7.6 days; p<0.001) accompanied by a sustained sex-difference in EE. In addition, female mice predominantly downsized gonadal AT whereas the relation between gonadal and total body fat was not altered in males. Accordingly, only females exhibited an increased rate of forskolin-stimulated lipolysis in AT associated with significantly higher glycerol concentrations, lower RER-values, and increased AT expression of adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Analysis of AT lipolysis in estrogen receptor alpha (ERα)-deficient mice revealed a reduced lipolytic rate in the absence of ERα exclusively in females. Finally, re-feeding caused BW-regain faster in males than in females. The present study shows sex-specific dynamics during BW-gain-loss-regain. Female mice responded to CR with an increase in lipolytic activity, and augmented lipid-oxidation leading to more efficient weight loss. These processes likely involve ERα-dependent signaling in AT and sexual dimorphic regulation of genes involved in lipid metabolism.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adipocytes / Adipose tissue / Adipose Tissue - metabolism / Animals / Biology / Body composition / Body fat / Body Weight / Body weight loss / Diabetes / Diet / Diet, High-Fat / Dietary restrictions / Drug dosages / Endocrinology / Energy expenditure / Estrogen Receptor alpha - metabolism / Estrogens / Fatty acids / Feeding / Female / Females / Food / Forskolin / Gain-Loss / Gender differences / Gene expression / Gene regulation / Glycerol / High fat diet / Homeostasis / Laboratory animals / Ligands / Lipase / Lipid metabolism / Lipolysis / Male / Males / Medicine / Metabolism / Mice / Mice, Inbred C57BL / Musculoskeletal system / Nutrition research / Obesity / Obesity - metabolism / Oxidation / Pharmacology / Phase measurement / Phosphorylation / Physiological aspects / Research design / Rodents / Sex / Sex differences / Sex Factors / Signaling / Studies / Triglycerides / Type 2 diabetes / Weight control / Weight Gain / Weight Loss / Weight reduction / Womens health