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miR155 deficiency aggravates high-fat diet-induced adipose tissue fibrosis in male mice
Kandy T Velázquez1, Reilly T Enos1, Meredith S Carson1
1Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina.
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.
Insights
Deleting microRNA-155 (miR155) in mice did not prevent high-fat diet obesity but worsened adipose tissue fibrosis. This suggests miR155 plays a role in regulating fibrosis during obesity development.
Area of Science:
- Molecular Biology
- Metabolic Disease Research
- RNA Biology
Background:
- Noncoding RNAs, including microRNAs (miRNAs), are increasingly recognized as key regulators of inflammatory and metabolic pathways.
- MicroRNA-155 (miR155) has been implicated in inflammatory responses and adipogenesis, suggesting a potential role in obesity.
- Understanding the specific function of miR155 in diet-induced obesity is crucial for developing targeted therapeutic strategies.
Purpose of the Study:
- To investigate the impact of global miR155 deletion on the development of high-fat diet (HFD)-induced obesity in mice.
- To determine if the absence of miR155 influences adipose tissue inflammation, fibrosis, and metabolic profiles.
- To test the hypothesis that miR155 deficiency would reduce adipose tissue inflammation and improve metabolic health under HFD conditions.
Main Methods:
- Male miR155 knockout (miR155-/-) and wild-type (WT) mice were fed a high-fat diet (HFD) or a low-fat diet for 20 weeks.
- Evaluated body weight, body composition (DEXA), adipose tissue inflammation markers (macrophage markers, inflammatory mediators), adiponectin, and adipogenic/fibrotic markers (PPAR-γ, Collagen I, III, VI).
- Assessed glucose metabolism and insulin resistance using HOMA-IR and glucose tolerance tests.
Main Results:
- miR155-/- HFD mice exhibited similar body weights but reduced visceral adipose tissue accumulation compared to WT HFD mice.
- Adipose tissue in miR155-/- HFD mice showed exacerbated fibrosis and decreased PPAR-γ protein levels.
- The absence of miR155 did not significantly alter adipose tissue inflammation or glucose metabolism.
Conclusions:
- Global deletion of miR155 does not prevent the development of obesity induced by a high-fat diet.
- Loss of miR155 exacerbates adipose tissue fibrosis, potentially by altering adipogenic processes.
- miR155 plays a role in modulating adipose tissue fibrosis, independent of its effects on inflammation and glucose metabolism in this model.
