Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet

Abstract Introduction Known for its neuroprotective properties, the ketogenic diet (KD) recently has been shown to prevent weight loss induced by chronic stress in rats, although the mechanisms remain to be elucidated. The obesity-resistant BALB/c mouse is susceptible to chronic stress–induced weigh...

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Main Authors: Ana L. Cantú-Ruiz, Diana Caballero-Hernández, Isaias Gutierrez-Leal, Ana C. Martínez-Torres, Ricardo Gomez-Flores, Patricia Tamez-Guerra, Reyes Tamez-Guerra, Cristina Rodríguez-Padilla
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Language:English
Published: BMC 2025-07-01
Series:BMC Nutrition
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Online Access:https://doi.org/10.1186/s40795-025-01129-8
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author Ana L. Cantú-Ruiz
Diana Caballero-Hernández
Isaias Gutierrez-Leal
Ana C. Martínez-Torres
Ricardo Gomez-Flores
Patricia Tamez-Guerra
Reyes Tamez-Guerra
Cristina Rodríguez-Padilla
author_facet Ana L. Cantú-Ruiz
Diana Caballero-Hernández
Isaias Gutierrez-Leal
Ana C. Martínez-Torres
Ricardo Gomez-Flores
Patricia Tamez-Guerra
Reyes Tamez-Guerra
Cristina Rodríguez-Padilla
author_sort Ana L. Cantú-Ruiz
collection DOAJ
description Abstract Introduction Known for its neuroprotective properties, the ketogenic diet (KD) recently has been shown to prevent weight loss induced by chronic stress in rats, although the mechanisms remain to be elucidated. The obesity-resistant BALB/c mouse is susceptible to chronic stress–induced weight loss, providing a useful model to study the interactions between diet and stress. Objective This study aimed to evaluate the potential of a ketogenic diet to prevent chronic stress-induced weight loss in the obesity-resistant BALB/c mouse strain. Method BALB/c mice of both sexes, were divided into groups: (1) standard chow, (2) KD, (3) standard chow + stress, and (4) KD + stress. The stress groups were subjected to a restraint stress protocol for 23 d, 4 h a day. Morphometric changes, glucose tolerance, plasmatic corticosterone levels, and circulating ketone bodies were evaluated. Results Levels of β-hydroxybutyrate increased in the KD group in both sexes. However, under stress, the increase in ketone bodies was lower in female mice. Compared with standard chow-fed groups, females on a KD gained significant body weight, an effect lost in females under stress, with decreasing fat tissue deposits. In male mice, although no changes in body weight were observed in the KD group, the mass of adipose tissue depots increased and remained unchanged under stress. Under chronic stress both standard chow and KD-fed mice lost weight. Under KD, female and male BALB/c mice exhibited decreased water and food intake, as well as reduced glucose tolerance, under resting and chronic stress conditions. Conclusions There is an interplay between chronic stress and ketogenic metabolism in BALB/c mice. In female mice, chronic stress interferes with ketogenesis, lowering beta-hydroxybutyrate levels and preventing weight gain whereas the KD inhibits chronic stress-induced glucose tolerance, this in a sex-dependent manner.
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spelling doaj-art-6cb4c465c92a43eb97ef971d4d0cc2792025-08-20T03:45:51ZengBMCBMC Nutrition2055-09282025-07-0111111010.1186/s40795-025-01129-8Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic dietAna L. Cantú-Ruiz0Diana Caballero-Hernández1Isaias Gutierrez-Leal2Ana C. Martínez-Torres3Ricardo Gomez-Flores4Patricia Tamez-Guerra5Reyes Tamez-Guerra6Cristina Rodríguez-Padilla7Universidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaUniversidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaUniversidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaUniversidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaUniversidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaUniversidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaUniversidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaUniversidad Autónoma de Nuevo León, Facultad de Ciencias Biológicas, Departamento de Microbiología e Inmunología, Laboratorio de Inmunología y VirologíaAbstract Introduction Known for its neuroprotective properties, the ketogenic diet (KD) recently has been shown to prevent weight loss induced by chronic stress in rats, although the mechanisms remain to be elucidated. The obesity-resistant BALB/c mouse is susceptible to chronic stress–induced weight loss, providing a useful model to study the interactions between diet and stress. Objective This study aimed to evaluate the potential of a ketogenic diet to prevent chronic stress-induced weight loss in the obesity-resistant BALB/c mouse strain. Method BALB/c mice of both sexes, were divided into groups: (1) standard chow, (2) KD, (3) standard chow + stress, and (4) KD + stress. The stress groups were subjected to a restraint stress protocol for 23 d, 4 h a day. Morphometric changes, glucose tolerance, plasmatic corticosterone levels, and circulating ketone bodies were evaluated. Results Levels of β-hydroxybutyrate increased in the KD group in both sexes. However, under stress, the increase in ketone bodies was lower in female mice. Compared with standard chow-fed groups, females on a KD gained significant body weight, an effect lost in females under stress, with decreasing fat tissue deposits. In male mice, although no changes in body weight were observed in the KD group, the mass of adipose tissue depots increased and remained unchanged under stress. Under chronic stress both standard chow and KD-fed mice lost weight. Under KD, female and male BALB/c mice exhibited decreased water and food intake, as well as reduced glucose tolerance, under resting and chronic stress conditions. Conclusions There is an interplay between chronic stress and ketogenic metabolism in BALB/c mice. In female mice, chronic stress interferes with ketogenesis, lowering beta-hydroxybutyrate levels and preventing weight gain whereas the KD inhibits chronic stress-induced glucose tolerance, this in a sex-dependent manner.https://doi.org/10.1186/s40795-025-01129-8Chronic stressKetogenic dietΒ-hydroxybutyrateObesity-resistanceGlucose toleranceSex-dependent
spellingShingle Ana L. Cantú-Ruiz
Diana Caballero-Hernández
Isaias Gutierrez-Leal
Ana C. Martínez-Torres
Ricardo Gomez-Flores
Patricia Tamez-Guerra
Reyes Tamez-Guerra
Cristina Rodríguez-Padilla
Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet
BMC Nutrition
Chronic stress
Ketogenic diet
Β-hydroxybutyrate
Obesity-resistance
Glucose tolerance
Sex-dependent
title Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet
title_full Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet
title_fullStr Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet
title_full_unstemmed Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet
title_short Chronic stress inhibits weight gain and decreases beta-hydroxybutyrate levels and glucose tolerance in female BALB/c fed a high-fat ketogenic diet
title_sort chronic stress inhibits weight gain and decreases beta hydroxybutyrate levels and glucose tolerance in female balb c fed a high fat ketogenic diet
topic Chronic stress
Ketogenic diet
Β-hydroxybutyrate
Obesity-resistance
Glucose tolerance
Sex-dependent
url https://doi.org/10.1186/s40795-025-01129-8
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