What is it about?
Brown adipocytes are specialized thermogenic cells able to dissipate nutritional energy in the form of heat, which is conducive to metabolic homeostasis. Obesity limits thermogenesis due to unknown inhibitory signals for brown fat. Here we identify CLCF1 signaling as a previously undescribed brake signal on thermogenesis, which is activated in obesity and inhibited during thermogenesis. CLCF1 activates CNTFR-STAT3 signaling pathway, thereafter STAT3 transcriptionally inhibits PGC-1α and PGC-1β expression, thus restraining mitochondrial biogenesis in brown adipocytes. Consequently, CLCF1 transgenic mice exhibit impaired energy expenditure and thermogenic capacity, and spontaneously develop metabolic abnormalities without external metabolic stress. Our finding defines CLCF1 signaling as an explanation for obesity-related brown adipocyte degeneration, which may be a target for intervention in metabolic disorders.
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Why is it important?
Our finding defines a novel function of CLCF1 in the regulation of adipocyte thermogenesis and identifies CLCF1-CNTFR-STAT3 signaling pathway as an explanation for obesity-related brown adipocyte degeneration, which may be a target for intervention in metabolic disorders.
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This page is a summary of: CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes, Proceedings of the National Academy of Sciences, August 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2305717120.
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