Crosstalk between metabolism and inflammation in the pathogenesis of nutrition-related metabolic diseases

Contact: PD Dr. Olga Ramich

Funding: German Center for Diabetes Research e. V. (DZD)

Chronic low-grade tissue inflammation plays an essential role in the pathogenesis of metabolic dysfunctions in obesity and type 2 diabetes. Underlying cellular and molecular mechanisms are in focus of this project. We recently identified (Murahovschi, Pivovarova et al. 2015; Tacke et al. 2017) 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 the 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 (Klimontov et al., 2018). Moreover, it can stimulate the differentiation of human macrophages towards a proinflammatory type.

Fig. 1: The protein WISP1 is increasingly produced in the visceral adipose tissue (VAT) and can induce insulin resistance in peripheral metabolic organs as well as facilitate the progression of chronic inflammation and fibrosis in liver and adipose tissue. Images: Adapted from Servier Medical Art by Servier (https://smart.servier.com/)

Our recent experiments showed that WISP1 inhibits insulin action in hepatocytes and muscle cells in vitro and thus promotes insulin resistance (Hörbelt et al. 2018). WISP1 is a target of WNT signaling which play an active role in mediating tissue fibrosis. Moreover, WISP1 also regulates adipocyte differentiation.

In our current project funded by DZD, we investigate the role of WISP1 in the pathogenesis of fibrosis and inflammation in liver and adipose tissue associated with metabolic dysfunctions. For this, we perform a mouse study, experiments in cell and tissue culture and analysis of human and mouse samples.