DGAT-driven futile lipid cycling has a pronounced, yet concealed, thermogenic function

Thermoregulation is an essential yet incompletely understood homeostatic process in mammals. UCP1-mediated thermogenesis, while efficient, is dispensable, suggesting the existence of alternative mechanisms. Using a pharmacogenetic approach, we show that the adipose tissue futile lipid cycling (FLC) contributes to UCP1-independent thermogenesis, with DGATs being involved in the regulation of FLC. The loss of DGAT-driven FLC-mediated thermogenesis is compensated for by the hierarchical recruitment of alternative mechanisms such as shivering and enhanced lipid catabolism mediated by AMPK activation. Consistently, pharmacological inhibition of muscle shivering or AMPK in FLC-deficient mice leads to an acute reduction in energy expenditure and hypothermia. These findings demonstrate a substantial thermogenic potential of FLC and suggest previously unappreciated flexibility and adaptability in regulating the core body temperature through adaptive changes in adipocyte metabolism.

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Publication Details

Journal
Cell Metabolism
Published
2026-01-01
DOI
https://doi.org/10.1016/j.cmet.2025.12.009
Citations
2
Primary Topic
Adipose Tissue and Metabolism
Type
article
Field-Weighted Citation Impact
65.68
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article

DGAT-driven futile lipid cycling has a pronounced, yet concealed, thermogenic function

Adhideb Ghosh, Christian Wolfrum, Jelena Zurkovic, Revati S. Dewal et al.
2 citations
Cell Metabolism
Adipose Tissue and Metabolism
65.68
article

DGAT-driven futile lipid cycling has a pronounced, yet concealed, thermogenic function

Adhideb Ghosh, Christian Wolfrum, Jelena Zurkovic, Revati S. Dewal, Radhika Khandelwal, Anand K. Sharma, Miroslav Baláž, Ruoman Wang, Tobias C. Walther, Fen Long, Christoph Thiele, Chunyan Wu, Klug Manuel, Robert V. Farese, Alaa Othman
article en
2 citations

Abstract

Thermoregulation is an essential yet incompletely understood homeostatic process in mammals. UCP1-mediated thermogenesis, while efficient, is dispensable, suggesting the existence of alternative mechanisms. Using a pharmacogenetic approach, we show that the adipose tissue futile lipid cycling (FLC) contributes to UCP1-independent thermogenesis, with DGATs being involved in the regulation of FLC. The loss of DGAT-driven FLC-mediated thermogenesis is compensated for by the hierarchical recruitment of alternative mechanisms such as shivering and enhanced lipid catabolism mediated by AMPK activation. Consistently, pharmacological inhibition of muscle shivering or AMPK in FLC-deficient mice leads to an acute reduction in energy expenditure and hypothermia. These findings demonstrate a substantial thermogenic potential of FLC and suggest previously unappreciated flexibility and adaptability in regulating the core body temperature through adaptive changes in adipocyte metabolism.

Cell Metabolism
Memorial Sloan Kettering Cancer Center (US), University of Bonn (DE), University of Zurich (CH), ETH Zurich (CH), Kettering University (US), Life Science Zurich (CH), Biomedical Research Center of the Slovak Academy of Sciences (SK), Nutrition Sciences (Belgium) (BE), Comenius University Bratislava (SK)
Affordable and clean energy
Openalex Percentile: Top 0%
Adipose Tissue and Metabolism
65.68
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