Loss of Oncostatin M receptor aggravates dyslipidemia, hepatic lipid accumulation and adipose tissue inflammation in Apoe-deficient mice fed a Western diet

Oncostatin M (OSM) is a member of the interleukin-6-type family and plays a pivotal role not only in inflammatory processes, but also in the regulation of metabolism. Previous studies revealed metabolically deleterious characteristics in mice lacking the OSM receptor beta gene (Osmr). Therefore, protective properties of OSM were suggested. To further investigate OSM-mediated effects on the lipid metabolism, we fed apolipoprotein E-deficient (Apoe-/-) and Apoe-/-Osmr-/- mice a Western-type diet for twelve weeks, and evaluated weekly weight gain, and serum lipid levels, lipoprotein fractions and hepatic lipid content after sacrifice. Furthermore, qPCR analyses of duodenal, hepatic and adipose tissue sample were performed. Although deficiency in Osmr did not result in body weight differences in the course of the diet, Apoe-/-Osmr-/- mice had increased serum concentrations of total and VLDL cholesterol, triglycerides, and free fatty acids when compared to Apoe-/- mice, in concordance with down-regulated hepatic lipoprotein receptor expression and up-regulated mRNA levels of lipases in adipose tissue. Moreover, most likely due to a repressed bile acid synthesis, Apoe-/-Osmr-/- mice showed an elevated liver cholesterol content. Furthermore slightly higher hepatic triglyceride levels were observed in Apoe-/-Osmr-/- mice, in line with down-regulated Cpt1a expression. In mice lacking the Osmr, qPCR analyses indicated a loss of anti-inflammatory macrophages in adipose tissue, but unaltered cytokine expression patterns. In light of our results, we hypothesize that OSM/OSMR/gp130 receptor complex conveys protective effects on lipid metabolism in Apoe-deficient mice.

Publication History

Article published online:
26 January 2022