Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

Mol Metab. 2018 Mar:9:176-186. doi: 10.1016/j.molmet.2018.01.015. Epub 2018 Feb 2.


Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals.

Objective: We attempted to address the issue of individual differences in the response to weight cycling in male mice.

Methods: We first exposed adult wild type mice to repeated cycles of high/low fat food. Next, using a lentiviral approach, we knocked-down or over-expressed miR-219 in the ventromedial hypothalamus (VMH) of an additional mouse cohort and performed a full metabolic assessment.

Results: Exposure of wild type males to weight cycling resulted in the division of the cohort into subsets of resistant versus metabolic-syndrome-prone (MS) animals, which differed in their metabolic profile and hypothalamic miR-219 levels. Lentiviral knock-down of miR-219 in the VMH led to exacerbation of metabolic syndrome. In contrast, over-expression of miR-219 resulted in moderation of the metabolic syndrome phenotype.

Conclusions: Our results suggest a role for miR-219 in the mediation of the metabolic phenotype resulting from repeated weight cycling.

Keywords: Diabetes; High fat diet; Metabolic syndrome; Ventromedial hypothalamus; Weight cycling; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caloric Restriction
  • Cell Line, Tumor
  • Diet, High-Fat
  • Female
  • Genetic Variation
  • Humans
  • Hypothalamus / metabolism*
  • Male
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Phenotype
  • Weight Gain*
  • Weight Loss*


  • MIRN219 microRNA, mouse
  • MicroRNAs