Genome-wide analysis of brown adipose tissue gene expression of IL15-depleted mice under normal diet or diet enriched with the beta3-adrenergic agonist CL 316243
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55057 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA238343
REPOSITORIES: GEO
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Project description:Chronic inflammation is one of the major players in the obesity related metabolic syndrome. However the various inflammatory mediators appear to promote insulin resistance directly or indirectly through their ability to induce the inflammatory cascade. Interleukin-15 (IL-15) is a pro-inflammatory cytokine that is involved in the pathogenesis of different autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease and type 1 diabetes. We postulated that as a pro-inflammatory cytokine, IL-15 promotes obesity during fat excess by promoting insulin resistance from tissues involved in energy metabolism. We used microarrays to characterize the gene expression profile of the brown adipose tissue of IL-15 mice under normal diet or diet enriched with the beta3-adrenergic agonist CL 316243 Total RNA obtained from adipose tissue of wt- or IL15-KO mice under normal diet or diet enriched with the beta3-adrenergic agonist CL 316243
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Abstract:
Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. While genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice (n=50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 (n=5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. While future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity.
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