title: Diet, gonadal sex, and sex chromosome complement influence white adipose tissue miRNA expression.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Link
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, 90095, Los Angeles, CA, USA.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Hasin-Brumshtein
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.affiliation: Department of Integrative Biology and Physiology, University of California, 90095, Los Angeles, CA, USA.|Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, 90095, Los Angeles, CA, USA.
authors.forename: Xuqi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Integrative Biology and Physiology, University of California, 90095, Los Angeles, CA, USA.|Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, 90095, Los Angeles, CA, USA.
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Arnold
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, 90095, Los Angeles, CA, USA.
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. reuek@ucla.edu.|Molecular Biology Institute, University of California, 90095, Los Angeles, CA, USA. reuek@ucla.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D005260:Female; D015723:Gene Library; D042341:Gonadal Hormones / Q000235:genetics / Q000378:metabolism; D006066:Gonads / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D025341:Principal Component Analysis; D012727:Sex Characteristics; D012730:Sex Chromosomes / Q000235:genetics*; D059467:Transcriptome
chemical_list: D042341:Gonadal Hormones; D035683:MicroRNAs
keywords: Adipose tissue; Sex chromosome; Sex differences; microRNA