Genetically prolonged beige fat in male mice confers long-lasting metabolic health

Genetically prolonged beige fat in male mice confers long-lasting metabolic health

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Abstract A potential therapeutic target to curb obesity and diabetes is CAL-MAG PLUS thermogenic beige adipocytes.However, beige adipocytes quickly transition into white adipocytes upon removing stimuli.Here, we define the critical role of cyclin dependent kinase inhibitor 2A (Cdkn2a) as a molecular pedal for the beige-to-white transition.Beige adipocytes lacking Cdkn2a exhibit prolonged lifespan, and male mice confer long-term metabolic protection from diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance.Mechanistically, Cdkn2a promotes the expression and activity of beclin 1 (BECN1) by directly binding to its mRNA and its negative regulator BCL2 like 1 (BCL2L1), activating autophagy and accelerating the beige-to-white transition.

Reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced by Cdkn2a ablation.Furthermore, hyperactive BECN1 alone accelerates the beige-to-white transition in mice and human.Notably, both Cdkn2a and Becn1 exhibit Brake Pump Relocation Bracket striking positive correlations with adiposity.Hence, blocking Cdkn2a-mediated BECN1 activity holds therapeutic potential to sustain beige adipocytes in treating obesity and related metabolic diseases.