Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation

Abstract

Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat REVIEW 14821October 28, 2014|Volume 20|Issue 40| WJG|www.wjgnet.com content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials.

Extrapancreatic effects of incretin hormones: evidence for weight‐independent changes in morphological aspects and oxidative status in insulin‐sensitive organs of the obese nondiabetic Zucker rat (ZFR)

“…Furthermore, independent of changes in body weight and glucose levels, exenatide increases both wholebody insulin sensitivity and insulin sensitivity-adjusted bcell mass in insulin-resistant obese nondiabetic fa/fa Zucker rats (ZFRs) (Gedulin et al 2005). These data are consistent with the observation that GLP-1RA improves hepatic insulin signaling while reducing hepatic fat deposition in animal models of nonalcoholic fatty liver disease (NAFLD) (Ding et al 2006;Gupta et al 2010Gupta et al , 2012Sharma et al 2011;Lee et al 2012Lee et al , 2012Lee et al , 2014Mells et al 2012;Blaslov et al 2014;Liu et al 2014;Wang et al 2014).…”

“…Even though Ex-4 was recently shown to reduce hepatic steatosis through activation of SIRT1 (Lee et al 2012(Lee et al , 2012(Lee et al , 2014, it remains unclear how GLP-1RA can restore redox balance in hepatocytes so rapidly. In addition to reducing OS after short-term exposure, and among many other effects on liver steatosis, GLP-1RA activation over longer periods of time influences the expression of many genes involved in hepatic lipid metabolism, as well as endoplasmic reticulum stress markers such as GRP78 and C/EBP (Blaslov et al 2014;Liu et al 2014;Wang et al 2014). In contrast to hepatocytes, skeletal muscle cells were significantly larger in Ex-4-treated ZFRs than in vehicletreated ZFRs.…”

Glucagon‐like peptide‐1 preserves non‐alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress‐associated pathway

“…In addition, inflammation and disordered cytokines in hepatocytes are believed to be involved in the pathogenesis of NAFLD. It is possible that GLP‐1 may ameliorate metabolic inflammation by reducing the release of inflammatory cytokines and by improving inflammatory pathways . In our study, we have not investigated the extent of inflammation, and we believe that more in‐depth research regarding GLP‐1 and inflammatory cytokine expression is needed in future studies.…”

Changes in the Intestinal Microbiome and Alcoholic and Nonalcoholic Liver Diseases: Causes or Effects?

“…GLP1 agonists can improve the lipid profile and increase metabolism via activation of peroxisome proliferator-activated receptor-α on the surface of hepatocytes, reducing the synthesis of apolipoprotein C, degrading fat in plasma, and removing triglycerides 61626364 . Administration of the probiotic VSL#3 for 4 months significantly reduced NASH in children, increasing levels of GLP1 65 .…”