| First Author | Wang J | Year | 2025 |
| Journal | Cell Metab | Volume | 37 |
| Issue | 11 | Pages | 2264-2279.e10 |
| PubMed ID | 41092902 | Mgi Jnum | J:374658 |
| Mgi Id | MGI:8260008 | Doi | 10.1016/j.cmet.2025.09.006 |
| Citation | Wang J, et al. (2025) Galnt2 neurons in the ventromedial hypothalamus counterregulate hypoglycemia via a brain-liver neurocircuit. Cell Metab 37(11):2264-2279.e10 |
| abstractText | 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 VMH(Galnt2)-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. |
