Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism

作者：Alain J. De Solís, Almudena Del Río-Martín, Jan Radermacher, Weiyi Chen, Lukas Steuernagel, Corinna A. Bauder, Fynn R. Eggersmann, Donald A. Morgan, Anna-Lena Cremer, Michael W. Sue, Maximilian Germer, Christian Kukat, Stefan Vollmar, Heiko Backes, Kamal Rahmouni, Peter Kloppenburg, Jens C. Brüning · 发表于：Nature Metabolism · 年份：2024 · DOI：10.1038/s42255-024-00987-z · 被引用次数：86 · 研究领域：Regulation of Appetite and Obesity、Biochemical Analysis and Sensing Techniques、Adipose Tissue and Metabolism

Abstract Agouti-related peptide (AgRP)-expressing and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combine non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons for comparing metabolic responses in male and female mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. We show that food intake is regulated by the additive effect of AgRP neuron activation and POMC neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated-versus-simultaneous regulation of AgRP and POMC neurons. We identify a neurocircuit engaging Npy1R-expressing neurons in the paraventricular nucleus of the hypothalamus, where activated AgRP neurons and inhibited POMC neurons cooperate to promote food consumption and activate Th + neurons in the nucleus tractus solitarii. Collectively, these results unveil how food intake is precisely regulated by the simultaneous bidirectional interplay between AgRP and POMC neurocircuits.