The Role of Gastrointestinal Hormones in Hepatic Lipid Metabolism

• Type of Material: Article
• Authors: Jamie Eugene Mells, Emory University; Frank A Anania, Emory University
• Language: English
• Date: 2013-11
• Publisher: Thieme Publishing
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 by Thieme Medical Publishers, Inc.
• Final Published Version (URL): https://www.thieme-connect.com/DOI/DOI?10.1055/s-0033-1358527
• Title of Journal or Parent Work: Seminars in Liver Disease
• ISSN: 0272-8087
• Volume: 33
• Issue: 4
• Start Page: 343
• End Page: 357
• Grant/Funding Information: This work was supported by Public Health Service Grant NIH DK062092 and Department of Veterans' Affairs Grant I01BX001746 both to FAA.; Jaime Eugene Mells is supported by the NIH K12 GM000680 NIGMS Fellowship in Research and Science Teaching (FIRST) Institutional Research and Academic Career Development Award.
• Keywords: enteroendocrine cells; lipotoxicity; nonalcoholic fatty liver disease; glucagon-like peptide 1 (GLP-1); neuropeptide YY (NPY)
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

Abstract

Hepatocellular accumulation of free fatty acids (FFAs) in the form of triglycerides constitutes the metabolic basis for the development of nonalcoholic fatty liver disease (NAFLD). Recent data demonstrate that excess FFA hepatocyte storage is likely to lead to lipotoxicity and hepatocyte apoptosis. Hence, FFA-mediated hepatocyte injury is a key contributor to the pathogenesis of nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis, obesity, type 2 diabetes, essential hypertension, and other common medical problems together comprise metabolic syndrome. Evidence suggests that peptide hormones from the L cells of the distal small intestine, which comprise the core of the enteroendocrine system (EES), play two key roles, serving either as incretins, or as mediators of appetite and satiety in the central nervous system. Recent data related to glucagon-like peptide-1 (GLP-1) and other known L-cell hormones have accumulated due to the increasing frequency of bariatric surgery, which increase delivery of bile salts to the hindgut. Bile acids are a key stimulus for the TGR5 receptor of the L cells. Enhanced bile-salt flow and subsequent EES stimulation may be central to elimination of hepatic steatosis following bariatric surgery. Although GLP-1 is a clinically relevant pharmacological analogue that drives pancreatic β-cell insulin output, GLP-1 analogues also have independent benefits via their effects on hepatocellular FFA metabolism. The authors also discuss recent data regarding the role of the major peptides released by the EES, which promote satiety and modulate energy homeostasis and utilization, as well as those that control fat absorption and intestinal permeability. Taken together, elucidating novel functions for EES-related peptides and pharmacologic development of peptide analogues offer potential far-ranging treatment for obesity-related human disease.