Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice

Abstract Dysregulation of energy metabolism, including hyperglycemia, insulin resistance and fatty liver have been reported in a substantial proportion of lean children. However, non-obese murine models recapitulating these features are lacking to study the mechanisms underlying the development of m...

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Main Authors: Amélie Joly, Jean-Louis Thoumas, Anne Lambert, Estelle Caillon, François Leulier, Filipe De Vadder
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Nutrition & Metabolism
Subjects:
Online Access:https://doi.org/10.1186/s12986-024-00879-9
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author Amélie Joly
Jean-Louis Thoumas
Anne Lambert
Estelle Caillon
François Leulier
Filipe De Vadder
author_facet Amélie Joly
Jean-Louis Thoumas
Anne Lambert
Estelle Caillon
François Leulier
Filipe De Vadder
author_sort Amélie Joly
collection DOAJ
description Abstract Dysregulation of energy metabolism, including hyperglycemia, insulin resistance and fatty liver have been reported in a substantial proportion of lean children. However, non-obese murine models recapitulating these features are lacking to study the mechanisms underlying the development of metabolic dysregulations in lean children. Here, we develop a model of diet-induced metabolic dysfunction without obesity in juvenile mice by feeding male and female mice a diet reflecting Western nutritional intake combined with protein restriction (mWD) during 5 weeks after weaning. mWD-fed mice (35% fat, 8% protein) do not exhibit significant weight gain and have moderate increase in adiposity compared to control mice (16% fat, 20% protein). After 3 weeks of mWD, juvenile mice have impaired glucose metabolism including hyperglycemia, insulin resistance and glucose intolerance. mWD also triggers hepatic metabolism alterations, as shown by the development of simple liver steatosis. Both male and female mice fed with mWD displayed metabolic dysregulation, which a probiotic treatment with Lactiplantibacillus plantarum WJL failed to improve. Overall, mWD-fed mice appear to be a good preclinical model to study the development of diet-induced metabolic dysfunction without obesity in juveniles.
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spelling doaj-art-cae283d4c8d14be3b8ae1814a81f4bf12024-12-08T12:21:02ZengBMCNutrition & Metabolism1743-70752024-12-0121111110.1186/s12986-024-00879-9Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile miceAmélie Joly0Jean-Louis Thoumas1Anne Lambert2Estelle Caillon3François Leulier4Filipe De Vadder5Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5242, UCBL Lyon-1Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5242, UCBL Lyon-1Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5242, UCBL Lyon-1Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5242, UCBL Lyon-1Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5242, UCBL Lyon-1Institut de Génomique Fonctionnelle de Lyon, École Normale Supérieure de Lyon, CNRS UMR 5242, UCBL Lyon-1Abstract Dysregulation of energy metabolism, including hyperglycemia, insulin resistance and fatty liver have been reported in a substantial proportion of lean children. However, non-obese murine models recapitulating these features are lacking to study the mechanisms underlying the development of metabolic dysregulations in lean children. Here, we develop a model of diet-induced metabolic dysfunction without obesity in juvenile mice by feeding male and female mice a diet reflecting Western nutritional intake combined with protein restriction (mWD) during 5 weeks after weaning. mWD-fed mice (35% fat, 8% protein) do not exhibit significant weight gain and have moderate increase in adiposity compared to control mice (16% fat, 20% protein). After 3 weeks of mWD, juvenile mice have impaired glucose metabolism including hyperglycemia, insulin resistance and glucose intolerance. mWD also triggers hepatic metabolism alterations, as shown by the development of simple liver steatosis. Both male and female mice fed with mWD displayed metabolic dysregulation, which a probiotic treatment with Lactiplantibacillus plantarum WJL failed to improve. Overall, mWD-fed mice appear to be a good preclinical model to study the development of diet-induced metabolic dysfunction without obesity in juveniles.https://doi.org/10.1186/s12986-024-00879-9Metabolic dysfunctionLeanJuvenileMASLD
spellingShingle Amélie Joly
Jean-Louis Thoumas
Anne Lambert
Estelle Caillon
François Leulier
Filipe De Vadder
Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice
Nutrition & Metabolism
Metabolic dysfunction
Lean
Juvenile
MASLD
title Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice
title_full Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice
title_fullStr Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice
title_full_unstemmed Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice
title_short Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice
title_sort protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice
topic Metabolic dysfunction
Lean
Juvenile
MASLD
url https://doi.org/10.1186/s12986-024-00879-9
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