Nikhil Seshadri
Pronouns: He/Him
Research Mentor(s): Nadejda Bozadjieva Kramer
Co-Presenter:
Research Mentor School/College/Department: Surgery / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 6 – 4:40pm – 5:30 pm
Room: Breakout room 2
Authors: Nikhil Seshadri, Nadejda Bozadjieva-Kramer PhD and Randy J Seeley, PhD
Presenter: 2
Abstract
Fibroblast Growth Factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Studies from our lab and others have shown that pharmacologically elevating FGF15/19 levels in rodent models of metabolic disease results in potent metabolic benefits, including increased energy expenditure, reduced adiposity, and improved lipid and glucose metabolism. We studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol and glucose metabolism under standard and western diets. When fed standard chow, high fat or a NASH-inducing AMLN (fat, fructose and cholesterol) diet, control and intestinal-derived FGF15 (FGF15INT-KO) knock out mice gained similar body weight, adiposity and did not show differences in glucose and pyruvate tolerance, or energy balance. FGF15INT-KO mice under these diet conditions had increased bile acid levels, pointing to the primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism. Importantly, FGF15INT-KO mice under AMLN diet showed reduced liver fibrosis. These studies show that intestinal FGF15 plays a specific and essential role in bile acid and cholesterol metabolism regulation but maybe dispensable for the regulation of body weight and glucose levels under a variety of dietary conditions.
Interdisciplinary, Natural/Life Sciences
