MiR155 deficiency aggravates high-fat diet-induced adipose tissue fibrosis in male mice.

Abstract

Noncoding RNAs are emerging as regulators of inflammatory and metabolic processes. There is evidence to suggest that miRNA155 (miR155) may be linked to inflammation and processes associated with adipogenesis. We examined the impact of global miRNA‐155 deletion (miR155−/−) on the development of high‐fat diet (HFD)‐induced obesity. We hypothesized that loss of miR155 would decrease adipose tissue inflammation and improve the metabolic profile following HFD feedings. Beginning at 4–5 weeks of age, male miR155−/− and wild‐type (WT) mice (n = 13–14) on a C57BL/6 background were fed either a HFD or low‐fat diet for 20 weeks. Body weight was monitored throughout the study. Baseline and terminal body composition was assessed by DEXA analysis. Adipose tissue mRNA expression (RT‐qPCR) of macrophage markers (F4/80, CD11c, and CD206) and inflammatory mediators (MCP‐1 and TNF‐α) as well as adiponectin were measured along with activation of NFκB‐p65 and JNK and PPAR‐γ. Adipose tissue fibrosis was assessed by picrosirius red staining and western blot analysis of Collagen I, III, and VI. Glucose metabolism and insulin resistance were assessed by Homeostatic Model Assessment – Insulin Resistance (HOMA‐IR), and a glucose tolerance test. Compared to WT HFD mice, miR155−/− HFD mice displayed similar body weights, yet reduced visceral adipose tissue accumulation. However, miR155−/− HFD displayed exacerbated adipose tissue fibrosis and decreased PPAR‐γ protein content. The loss of miR155 did not affect adipose tissue inflammation or glucose metabolism. In conclusion, miR155 deletion did not attenuate the development of the obese phenotype, but adipose tissue fibrosis was exacerbated, possibly through changes to adipogenic processes.