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.

Adipose Tissue Fibrosis: Mechanisms, Models, and Importance

“…Specifically, it has been found that miRNA155 (miR155) plays an important role in adipocyte differentiation into the white phenotype and activation of proinflammatory pathways [ 148 , 149 ]. By deleting miR155 and feeding male mice a high fat diet to induce obesity, it was found that this deletion caused mice to store less visceral adipose tissue but exacerbated adipose tissue fibrosis compared to wildtype mice fed a high fat diet [ 150 ]. This was surprising because other groups have shown that miR155 plays a role in promoting macrophage polarization to the M1 phenotype [ 151 , 152 , 153 ].…”

Macrophage tumor necrosis factor‐alpha deletion does not protect against obesity‐associated metabolic dysfunction

“…The HFD was a custom‐made purified HFD (4.57 kcal/g) comprised of 47%, 40%, and 13% of total calories from carbohydrate, fat, and protein, respectively, with saturated fat making up 12% of total calories in order to mimic the standard American diet (Bio‐Serv, Frenchtown, NJ). Details and previous use of this diet are provided elsewhere 16‐23 . Mice were housed, 3‐5/cage, maintained on a 12:12‐h light‐dark cycle in a low‐stress environment (22°C, 50% humidity, low noise), and given food and water ad libitum.…”

“…Details and previous use of this diet are provided elsewhere. [16][17][18][19][20][21][22][23] Mice were housed, 3-5/cage, maintained on a 12:12-h light-dark cycle in a low-stress environment (22°C, 50% humidity, low noise), and given food and water ad libitum. All methods were in accordance with the American Association for Laboratory Animal Science, and the Institutional Animal Care and Usage Committee of the University of South Carolina approved all experiments.…”

The role of microRNAs in the regulation of insulin signaling pathway with respect to metabolic and mitogenic cascades: A review

“…Moreover, it was reported that the overexpression of miR‐29a downregulated PPARδ and its coactivator PGC‐1α via binding to the 3′‐UTR of PPARδ in skeletal muscle cells . Furthermore, miR‐155 deletion decreased PPARγ protein content and exacerbated adipose tissue fibrosis in HFD mice . Among traditional Chinese herbs, Astragalus polysaccharides are known as enhancers of insulin sensitivity.…”

“…67 Furthermore, miR-155 deletion decreased PPARγ protein content and exacerbated adipose tissue fibrosis in HFD mice. 104 Among traditional Chinese herbs, Astragalus polysaccharides are known as enhancers of insulin sensitivity. These active components have significant antioxidant and immunomodulatory roles in improving T2D.…”