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MicroRNAs Regulated by Eicosapentaenoic Acid (EPA) in Brown, Subcutaneous, and visceral Adipose Tissue of Diet-Induced Obese Mice

ABSTRACT: To understand differences in microRNA (miRNA) signatures between two different diets with and without EPA in brown, subcutaneous, and viscerl tissue from C57BL/6 mice to understand mechanistic insight regarding their contribution to metabolic disorders in obesity. We performed small RNA-sequencing of brown, subcutaneous adipose from high fat diet (45% kcal from fat) and high fat diet supplemented with EPA (45% Kcal from fat, 6.75% EPA). Using the Gunaratne Next Generation pipeline (published in Creighton et al. 2009) miRNA expression profiles were identified. Counts of each unique read were normalized to total usable reads, and had 40 counts added. We mapped about 13.8 million sequence reads per sample to the Mus musculus genome (build mm 10). AS a total 1251 miRNAs were identified in three adipose tissue and out of which in bown adipose tissue 15 showd differential expression between BF-HF and BF-EPA .IN subcutaneous adipose tissue 3 miRNAs showed differntial expression between SUB-HF and SUB-EPA. EPA differentially regulate specific miRNAs expression in brown, subcutaneous, and visceral adipose tissue.

ORGANISM(S): Mus musculus

PROVIDER: GSE99506 | GEO | 2018/12/26

REPOSITORIES: GEO

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Project description:Background and objective: Combination antiretroviral therapy (cART) is associated with lipodystrophy i.e. loss of subcutaneous adipose tissue in abdomen, limbs and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulates in this region (“buffalo hump”). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1-infected cART-treated patients with (cART+LD+) and without (cART+LD-) lipodystrophy. Results: Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA, copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD-. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical vs. abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. Conclusions: As mtDNA is depleted even in the non-atrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal s.c. adipose tissue is in expression of homeobox genes. We used histology, microarray, polymerase chain reaction and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n=21) and cART+LD- (n=11). The study consists of 17 patients on antiretroviral treatment who have developed lipodystrophy and 11 patients that are on similar treatment but have not developped lipodystrophy. All patients are HIV+ and have 2 adipose tissue samples taken from them (dorsocervical+abdominal).

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MicroRNAs Regulated by Eicosapentaenoic Acid (EPA) in Brown, Subcutaneous, and visceral Adipose Tissue of Diet-Induced Obese Mice

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