Novel effect of glucagon-like peptide-2 for hepatocellular injury in a parenterally fed rat model of short bowel syndrome

Improvement in metabolic indices including thyroid hormones via enhanced absorption of nutrients by Teduglutide in short bowel syndrome

“…Apparently, this is the first report of reversal of cirrhosis with administration of teduglutide as evidenced by remission from hepatic encephalopathy, ascites and normalization of liver enzymes. This finding is consistent with a recent study which showed that low dose GLP-2 administration improves hepatic steatosis in parenterally fed rat model of short bowel syndrome [9] . Reversal in hepatic steatosis is attributed to increased splanchnic blood flow and improvement in cholestasis [11] , [12] .…”

“…Hepatocellular injury has been documented in patients with short bowel syndrome/intestinal failure and is attributed to lack of nutrient supply to liver by decrease in nutrients in the spared gut due to maldigestion and malabsorption [9] , [10] . Long-term parenteral support has been thought to delay onset of liver disorder by supplementation of nutrients directly to the liver through systemic circulation [3] , [5] , [8] .…”

Loss of Glp2r signaling activates hepatic stellate cells and exacerbates diet-induced steatohepatitis in mice

“…The current studies were prompted in part by questions surrounding the use of the GLP-2 analog teduglutide in human subjects with intestinal failure at risk for development of PN-associated hepatosteatosis (28) and the conflicting data surrounding the putative actions of GLP-2 in the liver (13,17,29). GLP-2 rapidly increases postprandial levels of TGs in mice, hamsters, and humans (30)(31)(32), suggesting that increased substrate availability may contribute to hepatosteatosis in the setting of sustained GLP-2R signaling.…”

“…Indeed, Taher and colleagues demonstrated increased hepatic lipogenesis in HFD-fed hamsters treated with GLP-2 as well as in rodent chow-fed (RC-fed) mice treated with GLP-2 (13). In contrast, treatment of HFDfed mice with the GLP-2R antagonist GLP-2(3-33) exacerbated hepatic steatosis in HFD-fed mice (17), whereas GLP-2 administration attenuated development of hepatosteatosis in PN-fed rats after small bowel resection (29). Our data, using administration of a degradation-resistant GLP-2R agonist, revealed no compelling effect of GLP-2R activation on hepatic steatosis in WT HFHC-fed mice.…”

The protective effects of hepatocyte growth factor on the intestinal mucosal atrophy induced by total parenteral nutrition in a rat model

“…Our previous study using a TPN rat model or a short bowel syndrome rat model with or without bowel resection showed that both ghrelin [ 7 ] and glucagon-like peptide-2 (GLP-2) [ 8 ] attenuated intestinal mucosal atrophy and IFALD [ 9 , 10 ]. However, the effect of ghrelin on intestinal mucosal atrophy was less marked than that of GLP-2, and a high dose of GLP-2 deteriorated the parenteral nutrition-associated liver disease (PNALD).…”