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This research investigates how succinate influences thermogenesis in brown adipocytes and prevents obesity.

June 17, 2026Open Access

Succinate Prevents Mice Obesity by Enhancing Brown Adipocyte Thermogenesis via the SDH-METTL3-HIF1A Pathway

Key Points

This research investigates how succinate influences thermogenesis in brown adipocytes and prevents obesity.
Dietary succinate supplementation was administered to mice on a high-fat diet
Serum succinate levels and METTL3 protein expression in brown adipocytes were measured
Mechanistic studies evaluated the role of m6A modification on Hif1a mRNA and its influence on HIF1A protein expression.
Succinate supplementation significantly elevated serum succinate levels.
Increased METTL3 expression resulted in higher m6A levels in Hif1a mRNA, enhancing HIF1A protein production.
HIF1A activation led to increased transcription of thermogenic genes in brown adipose tissue, boosting energy expenditure.

Abstract

Succinate, a tricarboxylic acid (TCA) cycle intermediate, is the essential signal molecule that links metabolic signals and inflammation. Dietary succinate supplementation has been reported to prevent obesity induced by a high-fat diet (HFD). However, the underlying mechanism remains elusive. Here, we found that dietary succinate elevated the serum succinate levels. Meanwhile, we found succinate increased methyltransferaselike 3 (METTL3) protein expression in brown adipocytes, thereby elevating N6-methyladenosine (m6A) levels in Hypoxia-inducible factor1-alpha (Hif1a) mRNA. Hif1a mRNA is recognized by the m6A-binding protein YTH domain-containing family protein 1 (YTHDF1), facilitating HIF1A protein expression. HIF1A activates the transcription of thermogenic genes, ultimately increasing brown adipose energy expenditure. Together, our research provided new insights into the effect of succinate on m6A modification in brown adipose tissue thermogenesis.

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