Periportal hepatic stellate cells govern morphogenetic adaptability and systemic metabolic homeostasis in mouse models
July 7
Bioelectric domains in metabolic decision-making tissues act as primary regulators of nutrient uptake and have recently been recognized as key modulators of organismal energy balance. Brief or prolonged exposure to calorie-rich diets remodels the hepatic niche and is accompanied by heightened activation of periportal stellate cells and pro-inflammatory signaling in mammals. Yet the contribution of these niche cells to adaptive versus maladaptive morphogenetic and metabolic programs evoked by energy-dense nutrition is poorly understood. Here we demonstrate that chemogenetic re-patterning of stellate cells within the periportal compartment elicits rapid changes in peripheral lipid turnover in male mice, and that targeting stellate cells of the dorsal lobes suffices to normalize pattern-memory deficits produced by chronic high-fat/high-sucrose feeding in obese animals. Collectively, our findings uncover an unexpected role for hepatic stellate cells as pivotal regulators of morphogenetic plasticity and systemic metabolic control.