Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance.

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. Previous reports of FGF15-/- mice have limited our understanding of gut-specific FGF15's role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance. We found that circulating levels of FGF19 were reduced in individuals with obesity and comorbidities, such as type 2 diabetes and metabolic dysfunction-associated fatty liver disease. Gene expression analysis of ileal FGF15-positive cells revealed differential expression during the obesogenic state. We fed standard chow or a high-fat metabolic dysfunction-associated steatohepatitis-inducing diet to control and intestine-derived FGF15-knockout (FGF15INT-KO) mice. Control and FGF15INT-KO mice gained similar body weight and adiposity and did not show genotype-specific differences in glucose, mixed meal, pyruvate, and glycerol tolerance. FGF15INT-KO mice had increased systemic bile acid levels but decreased cholesterol levels, pointing to a primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism when exposed to obesogenic diet. These studies show that intestinal FGF15 plays a specific role in bile acid and cholesterol metabolism regulation but is not essential for energy and glucose balance.

Liver Decompensation after Bariatric Surgery in the Absence of Cirrhosis.

PURPOSE: Metabolic dysfunction-associated fatty liver disease-related cirrhosis is possible at the time of bariatric surgery, complicated by further liver decompensation. Hepatic decompensation can also occur in the absence of cirrhosis but the presentation is less clear. METHODS: We analyze the clinical characteristics, histological findings, and management of patients without cirrhosis who developed hepatic decompensation after bariatric surgery in our single tertiary-care hospital. RESULTS: From 2014 to 2019, 6 patients underwent a transvenous liver biopsy for liver decompensation after bariatric surgery. Mean age at diagnosis was 44 years. The time between bariatric surgery and the onset of symptoms varied widely (min. 8 months, max. 17 years). Mean % of weight loss was high at 43%. The clinical presentation was as follows: fatigue and jaundice (5/6), leg edema (3/6), and ascites (1/6). Blood test showed increased transaminases (mean ALT 53 UI/L, mean AST 130 UI/L), bilirubin (mean 6 mg/dL), and INR (mean 1.5) with a low albumin level (mean 27 mg/dL). The hepatic venous pressure gradient was high (mean 10 mmHg). Histology revealed steatosis, hepatocyte ballooning but also portal inflammation with polymorphonuclear cells, and bile duct alterations. Mean fibrosis score was 2. The clinical course was favorable with nutritional support with a mean follow-up of 36 months. CONCLUSION: Liver decompensation in the absence of cirrhosis can occur after bariatric surgery with a highly variable delay. A special histological signature is present with the coexistence of steatosis, bile duct alterations, and portal inflammation. Substantial clinical improvement with appropriate nutritional support seems to be effective.

[An unusual case of olmesartan induced enteropathy]. / Un cas inhabituel d'entéropathie secondaire à la prise d'olmesartan.

Olmesartan induced enteropathy was first described in 2012. It is a rare adverse effect of this antihypertensive drug. The clinical presentation commonly includes severe chronic diarrhea leading to weight loss and a variable degree of dehydration. Histological findings are most commonly observed in the duodenum and consist of partial or total villous atrophy, increased intraepithelial lymphocytes and inflammation in the lamina propria. Involvement of gastric and colic mucosa has also been described. We report on the case of a 63-year-old man, treated by olmesartan, who presented with severe chronic diarrhea. Biopsies from different levels of the gastrointestinal tract revealed a pandigestive intraepithelial lymphocytosis.