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

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

Author information

1
Department of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel; Department of Stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, Munich, 80804, Germany. Electronic address: schatzyo@gmail.com.
2
Department of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel; Department of Stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, Munich, 80804, Germany.
3
Department of Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel; Department of Stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, Munich, 80804, Germany. Electronic address: alon.chen@weizmann.ac.il.

Abstract

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

PMID:
29398616
PMCID:
PMC5870106
DOI:
10.1016/j.molmet.2018.01.015
[Indexed for MEDLINE]
Free PMC Article

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