Nutrient infusion in the dorsal vagal complex controls hepatic lipid and glucose metabolism in rats

Hypothalamic regulation of lipid and glucose homeostasis is emerging, but whether the dorsal vagal complex (DVC) senses nutrients and regulates hepatic nutrient metabolism remains unclear. Here, we found in rats DVC oleic acid infusion suppressed hepatic secretion of triglyceride-rich very-low-density lipoprotein (VLDL-TG), which was disrupted by inhibiting DVC long-chain fatty acyl-CoA synthetase that in parallel disturbed lipid homeostasis during intravenous lipid infusion. DVC glucose infusion elevated local glucose levels similarly as intravenous glucose infusion and suppressed hepatic glucose production. This was independent of lactate metabolism as inhibiting lactate dehydrogenase failed to disrupt glucose sensing and neither could DVC lactate infusion recapitulate glucose effect. DVC oleic acid and glucose infusion failed to lower VLDL-TG secretion and glucose production in high-fat fed rats, while inhibiting DVC farnesoid X receptor enhanced oleic acid but not glucose sensing. Thus, an impairment of DVC nutrient sensing may lead to the disruption of lipid and glucose homeostasis in metabolic syndrome.