Down-regulation of miRNAs in the brain and development of diet-induced obesity

Int J Dev Neurosci. 2018 Feb:64:2-7. doi: 10.1016/j.ijdevneu.2017.06.005. Epub 2017 Jun 23.

Abstract

Novel therapeutic interventions for obesity and comorbid conditions require knowledge of the molecular elements playing a role in the development of obesity. Chronic low-grade inflammation has been consistently reported in obese individuals. In this study, we first determined whether key molecular modulators of inflammation, microRNA-155 (miR-155) and microRNA-146a (miR-146a), are regulated by an obesogenic diet within brain regions associated with reward, metabolism and energy balance. C57BL/6J mice were chronically exposed to a high-fat diet (HFD) or a standard chow (CTL). Significant reductions in the levels of miR-155 (82%) and miR-146a (41%) levels were observed within the nucleus accumbens of HFD mice compared to CTL. Further analysis of miR-155 regulation showed no significant changes in levels across peripheral tissue (white adipose, spleen, kidney or liver) between HFD and CTL mice. The effect of lower miR-155 on the development of obesity was determined by exposing wild-type (WT) and miR-155 knockout mice (miR-155 KO) to HFD. Male miR-155 KO gained significantly more weight than WT littermates. Metabolic analyses revealed that miR-155 KO significantly ate more HFD compared to WT, without differing in other metabolic measures including energy expenditure. Together, these data show that miR-155 is physiologically down-regulated after intake of an obesogenic diet, and that loss of miR-155 increases intake of an obesogenic diet. Moreover, these findings shed light on a potential miRNA-based mechanism contributing to the development of diet-induced obesity.

Keywords: Food intake; Inflammation; Nucleus accumbens; Obesity; miR-146a; miR-155.

MeSH terms

  • Adipose Tissue, White / metabolism
  • Adiposity / genetics
  • Animals
  • Body Weight / genetics
  • Brain / metabolism*
  • Diet, High-Fat
  • Down-Regulation
  • Eating / genetics
  • Energy Metabolism / genetics
  • Kidney / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Obesity / genetics
  • Obesity / metabolism*
  • Spleen / metabolism

Substances

  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Mirn155 microRNA, mouse