Chaperone-mediated autophagy controls brown adipose tissue thermogenic activity.

Alberto Mestres-Arenas, Tania Quesada-López, Albert Blasco-Roset, Aleix Gavaldà-Navarro, Francisco J Godoy-Nieto, Rubén Cereijo, Susmita Kaushik, Antonio Diaz, Marta Giralt, Francesc Villarroya, Ana Maria Cuervo, Joan Villarroya

Department of Biochemistry and Molecular Biomedicine and Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain. · pubmed

Paper

Abstract

Brown adipose tissue (BAT) protects against obesity, diabetes, and cardiovascular disease. During BAT activation, macroautophagy is inhibited, while chaperone-mediated autophagy (CMA) is induced, promoting thermogenic gene expression, adipokine release, oxidative activity, and lipolysis. Aging reduces BAT function and lowers levels of LAMP2A, the rate-limiting CMA component. Pharmacological CMA activation restores BAT activity in aged mice. To explore the CMA's role in BAT, we generated LAMP2A-deficient brown adipocytes and found that CMA regulates proteins essential for thermogenesis and metabolism. Blocking CMA in BAT reduced energy expenditure, raised blood triglycerides, impaired secretion, and led to an increase of thermogenesis repressors. These findings show that CMA is essential for maintaining BAT function, especially during adaptive thermogenesis. By degrading repressors of thermogenesis, CMA supports BAT activity under cold or metabolic stress. This work highlights CMA as a key regulator of BAT plasticity and a promising therapeutic target for treating age-related metabolic disorders.

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Research summary

Chaperone-mediated autophagy (CMA) is essential for maintaining brown adipose tissue function and thermogenic activity, particularly in the context of aging. This paper is relevant as it addresses the mechanisms underlying age-related metabolic decline and suggests a potential therapeutic target for improving metabolic health in aging.

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