Hepatic effects of sleeve gastrectomy regardless of weight loss

Non-Alcoholic Fatty Liver Disease (NAFLD) is a wide spectrum of liver disorders affecting as much as 30% of the adult population in western countries. Obesity leads to NAFLD development but could be reversed by reducing 5-10% of body weight. This weight loss can alleviate NAFLD symptoms and cause reduction of hepatic fat accumulation but is usually difficult to achieve and sustain for most obese patients. Bariatric surgeries are becoming popular, as they provide an efficient and safe mean to treat obesity. Complete resolution of NASH is achieved for 70% of patients, but the underlying mechanism are not fully understood. It is generally accepted that the effects of the surgery are in part independent of weight loss. To better understand these mechanisms, we preformed restrictive sleeve gastrectomy (SG), to leptin receptor-deficient mice (db/db). These mice suffer from chronic hyperphagia and are essentially resistant to the weight loss effects of the surgery, as they ultimately surpass their pre-operation weight. Surprisingly, SG operated mice show complete resolution of NAFLD one month following the surgery, and a reduction in liver enzymes levels when compared to pair-fed sham-operated mice. Using this established model and focusing on the liver as a main metabolic hub, we analyzed the liver transcriptomes of SG and sham-operated mice. We identified differentially regulated hepatic genes and pathways, and further compared our data with published human data of liver biopsies to refine the core interspecies pathways which correspond to the beneficial effects of bariatric surgery on the liver.