Journal Article

Diet, gonadal sex, and sex chromosome complement influence white adipose tissue miRNA expression

Cantor, Rita M., Hasin-Brumshtein, Yehudit, Arnold, Arthur P., Lusis, Aldons J., Reue, Karen, Chen, Xuqi, Link, Jenny C.

2017

Overview

Background MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by targeting specific mRNA species for degradation or interfering with translation. Specific miRNAs are key regulators of adipogenesis, and are expressed at different levels in adipose tissue from lean and obese mice. The degree of lipid accumulation and distribution of white adipose tissue differs between males and females, and it is unknown whether sex differences in adipose tissue-specific miRNA expression may contribute to this dimorphism. Typically, sex differences are attributed to hormones secreted from ovaries or testes. However, the sex chromosome complement (XX versus XY) is also a determinant of sex differences and may regulate miRNA expression in adipocytes. Results To identify sex differences in adipose tissue miRNA expression and to understand the underlying mechanisms, we performed high-throughput miRNA sequencing in gonadal fat depots of the Four Core Genotypes mouse model. This model, which consists of XX female, XX male, XY female, and XY male mice, allowed us to assess independent effects of gonadal type (male vs . female) and sex chromosome complement (XX vs . XY) on miRNA expression profiles. We have also assessed the effects of a high fat diet on sex differences in adipose tissue miRNA profiles. We identified a male–female effect on the overall miRNA expression profile in mice fed a chow diet, with a bias toward higher expression in male compared to female gonadal adipose tissue. This sex bias disappeared after gonadectomy, suggesting that circulating levels of gonadal secretions modulate the miRNA expression profile. After 16 weeks of high fat diet, the miRNA expression distribution was shifted toward higher expression in XY vs . XX adipose tissue. Principal component analysis revealed that high fat diet has a substantial effect on miRNA profile variance, while gonadal secretions and sex chromosome complement each have milder effects. Conclusions Our results demonstrate that the overall miRNA expression profile in adipose tissue is influenced by gonadal hormones and the sex chromosome complement, and that expression profiles change in response to gonadectomy and high fat diet. Differential miRNA expression profiles may contribute to sex differences in adipose tissue gene expression, adipose tissue development, and diet-induced obesity.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Adipocytes / Adipogenesis / Adipose tissue / Adipose Tissue, White - metabolism / Adipose tissues / Analysis / Animal Genetics and Genomics / Animals / Bias / Biomedical and Life Sciences / Body fat / Chromosomes / Complement / Diet / Diet, High-Fat / Dimorphism / Female / Gender aspects / Gender differences / Gene expression / Gene Library / Genetic aspects / Genomics / Genotypes / Gonadal Hormones - genetics / Gonadal Hormones - metabolism / Gonadectomy / Gonads - metabolism / High fat diet / Homeostasis / Hormones / Human and rodent genomics / Life Sciences / Lipids / Male / Males / Metabolism / Mice / Mice, Inbred C57BL / Microarrays / Microbial Genetics and Genomics / MicroRNA / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / Non-coding RNA / Nutrition research / Obesity / Ovaries / Plant Genetics and Genomics / Principal Component Analysis / Principal components analysis / Proteomics / Regulators / Research Article / Ribonucleic acid / RNA / Secretions / Sex / Sex Characteristics / Sex Chromosomes - genetics / Sex differences / Sex discrimination / Transcriptome