Distinguished Scientist Seminar Series featuring James Ntambi, PhD – “Hepatic Lipogenesis and Regulation of Systemic Metabolism”

IN PERSON

Distinguished Scientist Seminar Series

James M. Ntambi, PhD
Professor of Biochemistry
Steenbock Professor of Nutritional Sciences
University of Wisconsin-Madison

Location: New Research Building Auditorium and via Zoom: https://georgetown.zoom.us/j/99357306789

Title & Abstract: 

“Hepatic Lipogenesis and Regulation of Systemic Metabolism”

The overall interest is to identify the mechanisms by which hepatic deficiency of staeroyl-CoA desaturase-1 (SCD-1) enzyme reduces hepatic de novo fatty acid synthesis, gluconeogenesis, liver steatosis and protects against adiposity in response to high carbohydrate or high sugar diets. Stearoyl-CoA desaturase (SCD) is a critical regulator of fuel metabolism that catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleoyl- (18:1n9) and palmitoleoyl-CoA (16:1n7). SCD expression is elevated in human and rodent obese and insulin resistant states, suggesting that excess MUFA synthesis may contribute to metabolic disease development. Indeed, SCD1 deficient mouse models exhibited decreased hepatic de novo fatty acid synthesis, protection against diet induced adiposity, hepatic steatosis, and hyperglycemia but the mechanisms of this protection leading to such beneficial physiological phenotypes are not fully understood. Using a liver specific SCD1 knockout (LKO) mouse model fed a high carbohydrate diet (HCD), we show that hepatic SCD1 deficiency increases systemic glucose uptake. Glucose trasporter-1 (GLUT-1) enhanced glucose uptake in the liver while upregulated GLUT-4 increased glucose uptake in white and brown adipose tissues. The induction of glucose utilization in LKO mice correlated with dramatic increases in the expression and plasma levels of the fibroblast growth factor 21 (FGF21) and adiponectin; a haptokine and adipokine, respectively that are known to regulate whole body lipid and glucose metabolism. Feeding LKO mice with triolein, but not tristearin, supplemented HCD reduced FGF21 expression and plasma levels. Inhibition of SCD activity in primary hepatocytes induced FGf21 gene expression which was repressed by treatment with oleate but not stearate. We hypothesize that hepatic oleate levels modulate liver-fat crosstalk to regulate systemic glucose and lipid metabolism via FGF21-adiponectin axis.