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Non-alcoholic steatohepatitis (NASH) is associated with obesity and increased expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ). However, the relevance of hepatocyte PPARγ in NASH associated with obesity is still poorly understood. In this study, hepatocyte PPARγ was knocked out (Pparg ΔHep ) in male and female mice after the development of high-fat diet-induced obesity. The diet-induced obese mice were then maintained on their original diet or switched to a high fat, cholesterol, and fructose (HFCF) diet to induce NASH. Hepatic PPARγ expression was mostly derived from hepatocytes and increased by high fat diets. Pparg ΔHep reduced HFCF-induced NASH progression without altering steatosis, reduced the expression of key genes involved in hepatic fibrosis in HFCF-fed male and female mice, and decreased the area of collagen-stained fibrosis in the liver of HFCF-fed male mice. Moreover, transcriptomic and metabolomic data suggested that HFCF-diet regulated hepatic amino acid metabolism in a hepatocyte PPARγ-dependent manner. Pparg ΔHep increased betaine-homocysteine s-methyltransferase expression and reduced homocysteine levels in HFCF-fed male mice. In addition, in a cohort of 102 obese patients undergoing bariatric surgery with liver biopsies, 16 cases were scored with NASH and were associated with increased insulin resistance and hepatic PPARγ expression. Our study shows that hepatocyte PPARγ expression is associated with NASH in mice and humans. In male mice, hepatocyte PPARγ negatively regulates methionine metabolism and contributes to the progression of fibrosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Gastric bypass is one of the most commonly used surgical techniques for the management of morbid obesity. It is usually done as an open surgery procedure, and in recent years surgeons have begun to perform it via the laparoscopic approach. The aim of this paper is to describe our surgical technique for laparoscopic gastric bypass (LGBP) and present the short-term results., Materials and Methods: Between January 2000 and January 2002 we operated on 50 patients with morbid obesity who met criteria for bariatric surgery. The patients had a mean age of 34 years and a body mass index (BMI) of 47., Results: Conversion was necessary in 4 of the 50 patients (8%). Mean operating time was 181 min, with a difference of 60 min between the first 10 and last 10 cases. There was a 26% rate of complications, 14% of which were early (%<% 30 days) and 12% late (%>%30 days). Mean hospital stay was 4.5 days., Conclusion: LGBP is a technique with good short-term results as far as weight loss is concerned, although it has one of the most complex learning curves in laparoscopic surgery. Surgeons who regard gastric bypass as the technique of choice for the surgical management of morbid obesity should consider performing it via the laparoscopic approach.