The Same Metabolic Response to FGF21 Administration in Male and Female Obese Mice Is Accompanied by Sex-Specific Changes in Adipose Tissue Gene Expression.

Elena Makarova,Anastasia Dubinina,Tatiana Jakovleva,Antonina Kazantseva,Nadezhda Bazhan,Konstantin Baranov,Natalia Balybina

doi:10.3390/ijms221910561

Abstract

The preference for high-calorie foods depends on sex and contributes to obesity development. Fibroblast growth factor 21 (FGF21) beneficially affects taste preferences and obesity, but its action has mainly been studied in males. The aim of this study was to compare the effects of FGF21 on food preferences and glucose and lipid metabolism in C57Bl/6J male and female mice with diet-induced obesity. Mice were injected with FGF21 or vehicle for 7 days. Body weight, choice between standard (SD) and high-fat (HFD) diets, blood parameters, and gene expression in white (WAT) and brown (BAT) adipose tissues, liver, muscles, and the hypothalamus were assessed. Compared to males, females had a greater preference for HFD; less WAT; lower levels of cholesterol, glucose, and insulin; and higher expression of Fgf21, Insr, Ppara, Pgc1, Acca and Accb in the liver and Dio2 in BAT. FGF21 administration decreased adiposity; blood levels of cholesterol, glucose, and insulin; hypothalamic Agrp expression, increased SD intake, decreased HFD intake independently of sex, and increased WAT expression of Pparg, Lpl and Lipe only in females. Thus, FGF21 administration beneficially affected mice of both sexes despite obesity-associated sex differences in metabolic characteristics, and it induced female-specific activation of gene expression in WAT.

Highlights

We evaluated the effect of Fibroblast growth factor 21 (FGF21) on the metabolism and taste preferences of both male and female mice with diet-induced obesity
Adipose tissue is a direct target of the action of FGF21 [51], and it is in adipose tissue that we found a sex-specific response to FGF21 administration in the expression of genes related to lipid metabolism
In female mice with diet-induced obesity, as well as in male mice, FGF21 administration beneficially affected glucose and lipid metabolism and taste preferences, despite significant sex differences in adiposity rates and metabolic characteristics. In both females and males, FGF21 inhibited the consumption of HFD, and this effect was associated with the inhibition of Agoutirelated protein (Agrp) expression in the hypothalamus

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Obesity is a serious problem in modern society. Over the past few decades, the main factor contributing to the development of obesity has been overeating [1]. The preference for palatable, high-calorie food induces overeating and contributes to the epidemic prevalence of obesity [2,3]. In this regard, it is of particular interest to search for drugs that correct metabolic disorders associated with obesity and shift taste preferences toward food products with a balanced composition of macronutrients

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