Nutrient infusion in the dorsal vagal complex controls hepatic lipid and glucose metabolism in rats
Rosa J.W. Li,
Battsetseg Batchuluun,
Song-Yang Zhang,
Mona A. Abraham,
Beini Wang,
Yu-Mi Lim,
Jessica T.Y. Yue,
Tony K.T. Lam
Affiliations
Rosa J.W. Li
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada
Battsetseg Batchuluun
Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada
Song-Yang Zhang
Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada
Mona A. Abraham
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada
Beini Wang
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada
Yu-Mi Lim
Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada; Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
Jessica T.Y. Yue
Department of Physiology, University of Alberta, Edmonton, AB T6G 2H7, Canada
Tony K.T. Lam
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, UHN, MaRS Center, TMDT 101 College Street, 10-705, Toronto, ON M5G 1L7, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada; Corresponding author
Summary: 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.
