Endocrine Abstracts

Recent data suggest that not only caloric density but also macronutrient composition of diets can influence metabolism, body composition and the development of metabolic disorders. A limitation of previous studies was that effects were studied predominantly in males. To better understand potential differences in the response of males and females to manipulations of dietary macronutrients, our studies were undertaken in both sexes. As a dietary model, we used regular chow diet (CH), low carbohydrate-high fat diets of normal (LCHF-1) and low (LCHF-2) protein content as well as a high carbohydrate-high fat diet (HCHF). Purified diets (% of metabolizable energy, fat/protein/carbohydrate: Chow (CH, 16.7/19.0/64.3), protein matched LCHF-1 (78.7/19.1/2.2), ketogenic LCHF-2 (92.8/5.5/1.7) and HCHF (61.9/18.7/19.4)) were pair-fed isoenergetically for 4 weeks to male and female Wistar rats (12 weeks at start, n=7/group). At study end (6 h fasting, dark phase), blood samples and organs were collected. Compared to CH, all isoenergetically fed diets high in fat led to reduced body weight (BW) gain. This effect was seen in both sexes and was independent of carbohydrate content. However, despite lower BW, animals fed LCHF-1 and LCHF-2 but not HCFC exhibited a significant (*P<0.05; ***P<0.001) increase in visceral fat (%; g/g BW) in both sexes (male CH: 0.93±0.07, LCHF-1: 1.22±0.07***, LCHF-2: 1.26±0.07***, HCHF: 1.08±0.06, female CH: 0.65±0.05, LCHF-1: 0.93±0.08, LCHF-2: 1.03±0.09***, HCHF: 0.64±0.05). Notably, subcutaneous fat mass increased significantly only in males. Higher serum leptin was seen in all animals fed HF-diets (male CH: 2837±374, LCHF-1: 4094±366, LCHF-2: 4646±617*, HCHF: 4599±411*, female CH: 904±193, LCHF-1: 2433±434*, LCHF-2: 2355±446*, HCHF: 2157±311). In white adipose tissues (WAT) a pronounced increase in adipokine mRNA expression (leptin, adiponectin) was seen only in males. Furthermore, surrogate markers of lipid synthesis (FASN), transport (LPL) and storage (ATGL) in subcutaneous WAT were also increased only in male individuals on HF. These data strongly suggest that macronutrients affect lipid metabolism differently in males and females. If macronutrients also affect transformation of subcutaneous WAT into beige fat in a sex specific manner is currently under investigation.