Luengo Mateos, MaríaGonzalez Vila, AntíaVicente Dragano, Nathalia RomanelliOhinska, NataliiaSilveira Loureiro, MaríaGonzález Domínguez, MarcoEstévez Salguero, ÁnxelaNovelle Rodriguez, PaulaLópez Pérez, Miguel A.Barca Mayo, Olga2025-01-182025-01-182023-08-29Luengo-Mateos, M., González Vila, A., Dragano, N.R.V., Ohinska, N., Silveira-Loureiro, M., González-Domínguez, M., Estévez-Salguero, A., Novelle-Rodríguez, P., López, M., Barca-Mayo, O. (2023). Hypothalamic astrocytic-BMAL1 controls energy balance in a sex-dependent manner. “Cell Reports”, vol. 42, 112949.2211-1247https://hdl.handle.net/10347/38689Here, 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.eng© 2023 The Author(s). Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Circadian clockAstrocytesEnergy homeostasisHypothalamusBMAL1Sexual dymorphism241111 Neurofisiología241112 Fisiología del sistema nervioso central241104 Fisiología endocrinaHypothalamic astrocytic-BMAL1 regulates energy homeostasis in a sex-dependent mannerjournal article10.1016/j.celrep.2023.112949open access