• Kohli Research Lab

    The research work in Dr. Rohit Kohli’s laboratory focuses on the pathogenesis of obesity related nonalcoholic fatty liver disease (NAFLD). In particular, we study two broad areas of investigation related to obesity and NAFLD.
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    The first area is non-alcoholic fatty liver disease (NAFLD) pathogenesis. We focus on the role of lipotoxicity, reactive oxygen species, inflammatory pathways and endoplasmic reticulum stress in the generation and regulation of the extreme stage of this disease; nonalcoholic steatohepatitis (NASH). Our laboratory has contributed to the field by highlighting the role of fructose in triggering above mentioned oxidative injury and inflammation which results in fibrosis within the liver. We introduced a novel yet simple dietary model of murine NASH wherein the disease is recapitulated with all its essential hepatic histologic features (steatosis, inflammation and fibrosis) in a milieu of obesity and insulin resistance (See Figure 1).

    non-alcoholic fatty liver disease (NAFLD) pathogenesis
    Figure 1

    Our second area of research is the impact of bariatric surgery on non-alcoholic fatty liver disease (NAFLD) and bile acid physiology. In this area of research the laboratory works to understand the mechanism and impact of bariatric surgical procedures such as sleeve gastrectomy and roux-en-Y gastric bypass on nonalcoholic steatohepatitis (NASH) and other co-morbidities of obesity. Our research involves using small animal models of common and experimental bariatric procedures to study the role of bile acids in the improvements seen after bariatric surgery.

    We began this work by using an experimental bariatric procedure called ileal transposition in rats (see figure 1), but we’ve progressed to murine vertical sleeve gastrectomy (VSG), specifically its effects on intestinal adaptation. Recently, we are also using ileal enteroid cultures (see figure 2) for investigating the mechanistic role of bile acid triggered signaling pathways including the farnesoid x receptor (FXR) and its downstream effectors such as fibroblast growth factor (FGF19).  

    Impact of Bariatric Surgery on NAFLD and Bile acid physiology
    Figure 1 - Ileal transposition in rats, an experimental bariatric procedure.

    Figure 2 - Ileal enteroid cultures: Intestinal tissue from C57bl/6 mice was used to grow enteroids. This representative image shows Edu incorporation (yellow fluorescence) in ileal derived murine enteroid villous cells suggesting proliferative response.