Lipoprotein receptor SR-B1 deficiency enhances adipose tissue inflammation and reduces susceptibility to hepatic steatosis during diet-induced obesity in mice

Obesity is a worldwide epidemic associated with excessive lipid accumulation in adipose and non-adipose tissues, including the liver, an early feature in the development of non-alcoholic fatty liver disease (NAFLD). Several studies have linked NAFLD with a deranged high-density lipoprotein (HDL) metabolism. Scavenger receptor class B type 1 (SR-B1) is the major membrane HDL receptor and is involved in reverse cholesterol, but its role in obesity and NAFLD development is unclear. The aim of this thesis was to determine the effects of SR-B1 deficiency on plasma metabolic parameters and fat deposition in adipose tissue and liver during obesity. Male SR-B1 knock-out (SR-B1-/-) mice and wild-type (WT) littermates were fed for 12 weeks with a high-fat diet (HFD) to induce obesity. At the end of the intervention SR-B1-/- mice fed a HFD exhibited significantly increased levels of plasma total cholesterol, triglycerides (TG) and TNF-α, in association with hypertrophied adipocytes and macrophage-containing crown-like structures (CLS) in adipose tissue, compared to WT obese mice. Remarkably, obese SR-B1-/- mice exhibited attenuated liver TG content, dysregulation in hepatic gene expression profile, increased hepatic TG secretion, and altered hepatic fatty acid (FA) composition, compared to WT mice. These results provide the basis for further elucidation of SR-B1 role in obesity and fatty liver disease, two major worldwide public health issues that increase the risk of advanced chronic disease and mortality in the general population.Obesity is a worldwide epidemic associated with excessive lipid accumulation in adipose and non-adipose tissues, including the liver, an early feature in the development of non-alcoholic fatty liver disease (NAFLD). Several studies have linked NAFLD with a deranged high-density lipoprotein (HDL) metabolism. Scavenger receptor class B type 1 (SR-B1) is the major membrane HDL receptor and is involved in reverse cholesterol, but its role in obesity and NAFLD development is unclear. The aim of this thesis was to determine the effects of SR-B1 deficiency on plasma metabolic parameters and fat deposition in adipose tissue and liver during obesity. Male SR-B1 knock-out (SR-B1-/-) mice and wild-type (WT) littermates were fed for 12 weeks with a high-fat diet (HFD) to induce obesity. At the end of the intervention SR-B1-/- mice fed a HFD exhibited significantly increased levels of plasma total cholesterol, triglycerides (TG) and TNF-α, in association with hypertrophied adipocytes and macrophage-containing crown-like structures (CLS) in adipose tissue, compared to WT obese mice. Remarkably, obese SR-B1-/- mice exhibited attenuated liver TG content, dysregulation in hepatic gene expression profile, increased hepatic TG secretion, and altered hepatic fatty acid (FA) composition, compared to WT mice. These results provide the basis for further elucidation of SR-B1 role in obesity and fatty liver disease, two major worldwide public health issues that increase the risk of advanced chronic disease and mortality in the general population.