Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet

In animals, obesity caused by consumption of a sweet-fat diet (SFD) is the most adequate mouse model of human diet-induced obesity. Fibroblast growth factor 21 (FGF21) reduces body weight, beneficially affects taste preferences, and corrects glucose metabolism in obese mice. Sex is known to influenc...

Full description

Saved in:
Bibliographic Details
Main Authors: N. М. Bazhan, T. V. Jakovleva, A. Yu. Kazantseva, N. E. Kostina, P. E. Orlov, N. Yu. Balybina, K. О. Baranov, E. N. Makarova
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2023-07-01
Series:Вавиловский журнал генетики и селекции
Subjects:
Online Access:https://vavilov.elpub.ru/jour/article/view/3771
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832575018039508992
author N. М. Bazhan
T. V. Jakovleva
A. Yu. Kazantseva
N. E. Kostina
P. E. Orlov
N. Yu. Balybina
K. О. Baranov
E. N. Makarova
author_facet N. М. Bazhan
T. V. Jakovleva
A. Yu. Kazantseva
N. E. Kostina
P. E. Orlov
N. Yu. Balybina
K. О. Baranov
E. N. Makarova
author_sort N. М. Bazhan
collection DOAJ
description In animals, obesity caused by consumption of a sweet-fat diet (SFD) is the most adequate mouse model of human diet-induced obesity. Fibroblast growth factor 21 (FGF21) reduces body weight, beneficially affects taste preferences, and corrects glucose metabolism in obese mice. Sex is known to influence FGF21 effects in different models of diet-induced and hereditary obesity. In mice with SFD-induced obesity, the effects of FGF21 have been studied only in males. The aim of this study was to compare the effects of FGF21 on body weight, food preferences and glucose and lipid metabolism in C57Bl/6J male and female mice with SFD-induced obesity. Mice were fed with a diet consisting of standard chow, lard and cookies for 10 weeks, then they were injected with FGF21 (1 mg per 1 kg) or vehicle for 7 days. Body weight, weights of different types of food, blood parameters, glucose tolerance, gene and protein expression in the liver, gene expression in the white, brown adipose tissues, and the hypothalamus were assessed. FGF21 administration reduced body weight, did not alter total energy consumption, and activated orexigenic pathways of hypothalamus in mice of both sexes. However, sex dimorphism was found in the realization of the orexigenic FGF21 action at the transcriptional level in the hypothalamus. Metabolic effects of FGF21 were also sex-specific. Only in males, FGF21 exerted beneficial antidiabetic action: it reduced fatty acid and leptin plasma levels, improved glucose-tolerance, and upregulated hepatic expression of Ppargc1, Fasn, Accα, involved in lipid turnover, gene Insr and protein glucokinase, involved in insulin action. Only in obese females, FGF21 induced preference of standard diet to sweet food. Thus, in mouse model of obesity induced by consumption of a sweet-fat diet, the catabolic effect of FGF21 was not sex-specific and hormonal, transcriptional and behavioral effects of FGF21 were sex-specific. These data suggest elaboration of different approaches to use FGF21 analogs for correction of metabolic consequences of obesity in different sexes.
format Article
id doaj-art-58ef981040e84fad918499dad84d10c5
institution Kabale University
issn 2500-3259
language English
publishDate 2023-07-01
publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
record_format Article
series Вавиловский журнал генетики и селекции
spelling doaj-art-58ef981040e84fad918499dad84d10c52025-02-01T09:58:12ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592023-07-0127433334110.18699/VJGB-23-401358Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat dietN. М. Bazhan0T. V. Jakovleva1A. Yu. Kazantseva2N. E. Kostina3P. E. Orlov4N. Yu. Balybina5K. О. Baranov6E. N. Makarova7Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesIn animals, obesity caused by consumption of a sweet-fat diet (SFD) is the most adequate mouse model of human diet-induced obesity. Fibroblast growth factor 21 (FGF21) reduces body weight, beneficially affects taste preferences, and corrects glucose metabolism in obese mice. Sex is known to influence FGF21 effects in different models of diet-induced and hereditary obesity. In mice with SFD-induced obesity, the effects of FGF21 have been studied only in males. The aim of this study was to compare the effects of FGF21 on body weight, food preferences and glucose and lipid metabolism in C57Bl/6J male and female mice with SFD-induced obesity. Mice were fed with a diet consisting of standard chow, lard and cookies for 10 weeks, then they were injected with FGF21 (1 mg per 1 kg) or vehicle for 7 days. Body weight, weights of different types of food, blood parameters, glucose tolerance, gene and protein expression in the liver, gene expression in the white, brown adipose tissues, and the hypothalamus were assessed. FGF21 administration reduced body weight, did not alter total energy consumption, and activated orexigenic pathways of hypothalamus in mice of both sexes. However, sex dimorphism was found in the realization of the orexigenic FGF21 action at the transcriptional level in the hypothalamus. Metabolic effects of FGF21 were also sex-specific. Only in males, FGF21 exerted beneficial antidiabetic action: it reduced fatty acid and leptin plasma levels, improved glucose-tolerance, and upregulated hepatic expression of Ppargc1, Fasn, Accα, involved in lipid turnover, gene Insr and protein glucokinase, involved in insulin action. Only in obese females, FGF21 induced preference of standard diet to sweet food. Thus, in mouse model of obesity induced by consumption of a sweet-fat diet, the catabolic effect of FGF21 was not sex-specific and hormonal, transcriptional and behavioral effects of FGF21 were sex-specific. These data suggest elaboration of different approaches to use FGF21 analogs for correction of metabolic consequences of obesity in different sexes.https://vavilov.elpub.ru/jour/article/view/3771fgf21obesitysex differencesliveradipose tissuehypothalamusfood intakegene expression
spellingShingle N. М. Bazhan
T. V. Jakovleva
A. Yu. Kazantseva
N. E. Kostina
P. E. Orlov
N. Yu. Balybina
K. О. Baranov
E. N. Makarova
Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet
Вавиловский журнал генетики и селекции
fgf21
obesity
sex differences
liver
adipose tissue
hypothalamus
food intake
gene expression
title Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet
title_full Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet
title_fullStr Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet
title_full_unstemmed Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet
title_short Studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet-fat diet
title_sort studying sex differences in responses to fibroblast growth factor 21 administration in obese mice consuming a sweet fat diet
topic fgf21
obesity
sex differences
liver
adipose tissue
hypothalamus
food intake
gene expression
url https://vavilov.elpub.ru/jour/article/view/3771
work_keys_str_mv AT nmbazhan studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet
AT tvjakovleva studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet
AT ayukazantseva studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet
AT nekostina studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet
AT peorlov studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet
AT nyubalybina studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet
AT kobaranov studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet
AT enmakarova studyingsexdifferencesinresponsestofibroblastgrowthfactor21administrationinobesemiceconsumingasweetfatdiet