Hypothalamic astrocytic-BMAL1 regulates energy homeostasis in a sex-dependent manner
María Luengo-Mateos, Antía González-Vila, Nathalia Romanelli Vicente Dragano, N. V. Ohinska, María Silveira-Loureiro, Marco González-Domínguez, Ánxela Estévez‐Salguero, Paula Novelle-Rodríguez, Miguel López, Olga Barca‐Mayo
Abstract
Here, we demonstrate that hypothalamic astrocytic BMAL1 computes cyclic metabolic information to optimize energetic resources in a sexually dimorphic manner. Knockdown of BMAL1 in female astrocytes leads to negative energy balance and alters basal metabolic cycles without affecting circadian locomotor activity. Thus, astrocytic BMAL1 contributes to the control of energy balance through the modulation of the metabolic rate, hepatic and white adipose tissue lipogenesis, and the activity of brown adipose tissue. Importantly, most of these alterations are specific to hypothalamic astrocytic BMAL1. Moreover, female mice with BMAL1 knockdown in astrocytes exhibited a "male-like" metabolic obese phenotype when fed a high-fat diet. Overall, our results suggest a sexually dimorphic effect of astrocytic BMAL1 on the regulation of energy homeostasis, which may be of interest in the physiopathology of obesity and related comorbidities.