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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

β-hydroxybutyrate (BHB) serves as an alternative cellular fuel during states of low glucose availability, such as fasting or carbohydrate restriction, when the body shifts to using fats and ketone bodies for energy. While BHB has shown potential metabolic benefits, its mechanisms of action in the context of obesity are not fully understood. In this study, we examined the effects of BHB supplementation on subcutaneous adipose tissue (SAT) metabolism in a diet-induced obesity (DIO) mouse model. Adult male mice were first fed a high-fat diet for six weeks, followed by a standard diet with or without BHB supplementation for an additional six weeks. BHB supplementation led to significant body weight loss independent of food intake. This weight reduction was associated with decreased adipocyte differentiation, reflected by reduced peroxisome proliferator-activated receptor gamma (PPARγ) protein levels and lower uncoupling protein 1 (UCP1) expression, indicating altered SAT function. Transcriptomic analysis of SAT revealed upregulation of genes involved in fatty acid activation and transport (e.g., Slc27a2, Plin5, Acot4, Acsm3, Rik). Functional enrichment highlighted the activation of the PPAR signaling pathway and enrichment of peroxisomal components in the BHB group. Together, these results suggest that BHB promotes lipid remodeling in SAT, enhancing fatty acid metabolism while suppressing thermogenic pathways, and thus may represent a novel mechanism contributing to adiposity reduction and metabolic improvement.

Details

Title
β-Hydroxybutyrate Reduces Body Weight by Modulating Fatty Acid Oxidation and Beiging in the Subcutaneous Adipose Tissue of DIO Mice
Author
Heras Violeta 1 ; Mela, Virginia 1   VIAFID ORCID Logo  ; Kompella Pallavi 2 ; Rojano Elena 3   VIAFID ORCID Logo  ; Paz-López, Guillermo 4   VIAFID ORCID Logo  ; Hurtado-García, Lucia 5   VIAFID ORCID Logo  ; Ortega-Gomez, Almudena 1   VIAFID ORCID Logo  ; García-López, Maria José 6   VIAFID ORCID Logo  ; García-Martín, María Luisa 7   VIAFID ORCID Logo  ; Ranea Juan A. G. 8 ; Tinahones, Francisco J 6 ; Moreno-Indias, Isabel 1   VIAFID ORCID Logo 

 Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29590 Málaga, Spain; [email protected] (E.R.); [email protected] (G.P.-L.); [email protected] (L.H.-G.); [email protected] (A.O.-G.); [email protected] (M.J.G.-L.); [email protected] (M.L.G.-M.); [email protected] (J.A.G.R.); [email protected] (F.J.T.); [email protected] (I.M.-I.), Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain, Center for Biomedical Network Research (CIBER) in Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain 
 Nucleus, Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA; [email protected] 
 Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29590 Málaga, Spain; [email protected] (E.R.); [email protected] (G.P.-L.); [email protected] (L.H.-G.); [email protected] (A.O.-G.); [email protected] (M.J.G.-L.); [email protected] (M.L.G.-M.); [email protected] (J.A.G.R.); [email protected] (F.J.T.); [email protected] (I.M.-I.), Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Bulevar Louis Pasteur, 31, 29010 Málaga, Spain, Center for Biomedical Network Research on Rare Diseases (CIBERER), Avenue. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029 Madrid, Spain 
 Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29590 Málaga, Spain; [email protected] (E.R.); [email protected] (G.P.-L.); [email protected] (L.H.-G.); [email protected] (A.O.-G.); [email protected] (M.J.G.-L.); [email protected] (M.L.G.-M.); [email protected] (J.A.G.R.); [email protected] (F.J.T.); [email protected] (I.M.-I.) 
 Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29590 Málaga, Spain; [email protected] (E.R.); [email protected] (G.P.-L.); [email protected] (L.H.-G.); [email protected] (A.O.-G.); [email protected] (M.J.G.-L.); [email protected] (M.L.G.-M.); [email protected] (J.A.G.R.); [email protected] (F.J.T.); [email protected] (I.M.-I.), Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Bulevar Louis Pasteur, 31, 29010 Málaga, Spain 
 Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29590 Málaga, Spain; [email protected] (E.R.); [email protected] (G.P.-L.); [email protected] (L.H.-G.); [email protected] (A.O.-G.); [email protected] (M.J.G.-L.); [email protected] (M.L.G.-M.); [email protected] (J.A.G.R.); [email protected] (F.J.T.); [email protected] (I.M.-I.), Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Málaga, Spain, Center for Biomedical Network Research (CIBER) in Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain, Department of Medicine and Dermatology, Faculty of Medicine, University of Malaga, 29010 Malaga, Spain 
 Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29590 Málaga, Spain; [email protected] (E.R.); [email protected] (G.P.-L.); [email protected] (L.H.-G.); [email protected] (A.O.-G.); [email protected] (M.J.G.-L.); [email protected] (M.L.G.-M.); [email protected] (J.A.G.R.); [email protected] (F.J.T.); [email protected] (I.M.-I.), Biomedical Magnetic Resonance Laboratory-BMRL, Andalusian Public Foundation Progress and Health-FPS, 41092 Seville, Spain 
 Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29590 Málaga, Spain; [email protected] (E.R.); [email protected] (G.P.-L.); [email protected] (L.H.-G.); [email protected] (A.O.-G.); [email protected] (M.J.G.-L.); [email protected] (M.L.G.-M.); [email protected] (J.A.G.R.); [email protected] (F.J.T.); [email protected] (I.M.-I.), Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Bulevar Louis Pasteur, 31, 29010 Málaga, Spain, Center for Biomedical Network Research on Rare Diseases (CIBERER), Avenue. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, 28029 Madrid, Spain, Spanish National Bioinformatics Institute (INB/ELIXIR-ES), Instituto de Salud Carlos III (ISCIII), 28020 Madrid, Spain 
First page
5064
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3217734460
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.