Molecular regulation of adipose tissue and liver metabolism by nutrition

Contact: PD Dr. Olga Ramich

In the focus of this project is the impact of nutrition on cellular and molecular mechanisms in human adipose tissue and in the liver, chronical metabolism-related tissue inflammation, and its role in the development of metabolic dysfunctions in obesity and type 2 diabetes. In particular, we observed manifested effects of dietary proteins, saturated and unsaturated fatty acids, flavonoids and glucosinolates on insulin signaling, glucose and lipid metabolism, cytokine and adipokine profiles and inflammatory processes in tissue samples and in isolated blood cells and adipocytes.

Further, we recently identified the Wingless-type signaling pathway protein-1 (WISP1) as a novel adipokine which secretion into the circulation is increased in severely obese subjects (Fig. 1). As we could show in a clinical trial, visceral adipose tissue is a main source of circulating WISP1. The intensity of WISP1 production is associated with a stage of insulin resistance as well as with a secretion of inflammatory markers. Moreover, it can stimulate the differentiation of human macrophages towards a proinflammatory type. Our recent experiments showed that WISP1 inhibits insulin action in hepatocytes and muscle cells in vitro and thus promotes insulin resistance. WISP1 is a target of WNT signaling which play an active role in mediating tissue fibrosis. Moreover, WISP1 also regulates adipocyte differentiation.

In the very recent study, we investigate the role of WISP1 in the metabolic regulation and in the pathogenesis of fibrosis and inflammation in a mouse model of WISP1 knockout and in human liver and adipose tissue samples. Further, we investigate the WISP1 effect on the adipocyte differentiation in primary adipocyte culture.