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Review
. 2025 Aug 11.
doi: 10.1007/s13105-025-01117-3. Online ahead of print.

The multifaceted regulation of white adipose tissue browning and their therapeutic potential

Abhishek Satheesan  1 , Janardanan Kumar  2 , Kakithakara Vajravelu Leela  1 , Rahul Harikumar Lathakumari  1 , Matcha Angelin  1 , Ria Murugesan  1 , Venkata Chaithanya  1
Affiliations
Review

The multifaceted regulation of white adipose tissue browning and their therapeutic potential

Abhishek Satheesan et al. J Physiol Biochem. .

Abstract

Adipose tissue browning, the conversion of white adipose tissue (WAT) into brown or beige adipose tissue, offers potential for combating obesity and metabolic disorders. This review delves in to the transcriptional and epigenetic regulation of WAT browning and how it impacts metabolic health and its significance in various disease conditions. Further the review explains how various external factors such as diet and exercise play an influential role in the regulation of WAT browning. UCP1 gene, which plays a crucial role in cellular thermogenesis is found to be the major mediator of this phenomenon along with functional dynamics of mitochondria. Gut microbiome has been another focus point in this review that highlights how alterations to the composition of different species of bacteria in gut microbiome can directly influence WAT browning. Finally the review discusses the various pharmaceutical and neutraceutical options under research that targets WAT browning to improve metabolic status of an individual. Therapeutic strategies include β3-adrenergic receptor agonists, GLP-1 receptor agonists, AMPK activators, and natural compounds such as capsaicin and resveratrol. Emerging CRISPR/Cas9 gene therapies aim to induce WAT browning. Clinical evidence to prove the significance of this phenomena is currently limited but growing rapidly as seen in the number of clinical trials that are undergoing currently, therefore the review strongly rely upon animal model and cell culture based studies to justify this area of novel research. Despite its potential, challenges like individual variability, long-term safety, and complex gut microbiome interactions remain. Future research should target novel pathways, optimize therapeutic regimens, and personalize treatments.

Keywords: Browning; Epigenetics; Metabolism; Microbiota; Therapeutics; White adipose tissue.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests.

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