Products Cited in Publications Worldwide Galnt2 neurons in the ventromedial hypothalamus counterregulate hypoglycemia via a brain-liver neurocircuit

Galnt2 neurons in the ventromedial hypothalamus counterregulate hypoglycemia via a brain-liver neurocircuit

Wang, Junjie; Sun, Xinyuan; Gong, Xiangfei; Dai, Wenling; Hong, Hao; Jiang, Li; Wang, Zhonglong; Tang, Zhiyuan; Wu, Xiaobo; Sun, Peng

DOI: PMID:

Abstract

The brain relies heavily on glucose for energy resources, and thus prompt counterregulatory responses to hypoglycemia in connection with glucose production are fundamental. We identified a biphasic pattern in blood and hypothalamic glucose dynamics during prolonged fasting, revealing an additional threshold-dependent mechanism for counterregulation. This mechanism is mediated by a ventromedial hypothalamus (VMH)→paraventricular hypothalamic nucleus (PVH)→lateral paragigantocellular nucleus (LPGi)→liver neurocircuit that detects neuroglycopenia and transmits neural signals to drive hepatic glucose production via intrahepatic sympathetic activation. Using viral tracing, single-nucleus RNA sequencing, and various unbiased methods, we identified Galnt2 as both a genetic marker and molecular brake of VMH glucose-inhibited neurons, modulating the glycemic threshold for hypoglycemia perception and metabolic homeostasis. Our results highlight a VMHGalnt2-originated brain-liver neurocircuit that perceives and counterregulates hypoglycemia and may pave the way to innovative therapeutic strategies against metabolic disorders characterized by glucose dysregulation.

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