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.
| Original language | English |
|---|---|
| Pages (from-to) | 176-186 |
| Number of pages | 11 |
| Journal | Molecular Metabolism |
| Volume | 9 |
| DOIs | |
| State | Published - Mar 2018 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2018 The Authors
Funding
A.C. is the head of the Max Planck Society–Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics. This work is supported by: an FP7 Grant from the European Research Council (260463, A.C.); a research grant from the Israel Science Foundation (1565/15, A.C.); the ERANET Program, supported by the Chief Scientist Office of the Israeli Ministry of Health (3-11389, A.C.); the project was funded by the Federal Ministry of Education and Research under the funding code 01KU1501A (A.C.); research support from Roberto and Renata Ruhman (A.C.); research support from Bruno and Simone Licht; I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant no. 1916/12 to A.C.); the Nella and Leon Benoziyo Center for Neurological Diseases (A.C.); the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics (A.C.); the Perlman Family Foundation, founded by Louis L. and Anita M. Perlman (A.C.); the Adelis Foundation (A.C.); the Marc Besen and the Pratt Foundation (A.C.); and the Irving I. Moskowitz Foundation (A.C.). We thank Mr. Sharon Ovadia for his devoted assistance with animal care. A.C. is the head of the Max Planck Society–Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics. This work is supported by: an FP7 Grant from the European Research Council ( 260463 , A.C.); a research grant from the Israel Science Foundation ( 1565/15 , A.C.); the ERANET Program, supported by the Chief Scientist Office of the Israeli Ministry of Health ( 3-11389 , A.C.); the project was funded by the Federal Ministry of Education and Research under the funding code 01KU1501A (A.C.); research support from Roberto and Renata Ruhman (A.C.); research support from Bruno and Simone Licht ; I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant no. 1916/12 to A.C.); the Nella and Leon Benoziyo Center for Neurological Diseases (A.C.); the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics (A.C.); the Perlman Family Foundation , founded by Louis L. and Anita M. Perlman (A.C.); the Adelis Foundation (A.C.); the Marc Besen and the Pratt Foundation (A.C.); and the Irving I. Moskowitz Foundation (A.C.). We thank Mr. Sharon Ovadia for his devoted assistance with animal care.
| Funders | Funder number |
|---|---|
| Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics | |
| Irving I. Moskowitz Foundation | |
| Marc Besen | |
| Nella and Leon Benoziyo Center for Neurological Diseases | |
| Roberto and Renata Ruhman | 1916/12 |
| Weizmann Institute of Science Laboratory for Experimental Neuropsychiatry and Behavioral Neurogenetics | |
| Achelis Foundation | |
| Seventh Framework Programme | 260463 |
| Pratt Foundation | |
| Perlman Family Foundation | |
| European Commission | |
| Bundesministerium für Bildung und Forschung | 01KU1501A |
| Israel Science Foundation | 1565/15 |
| Max-Planck-Gesellschaft | |
| Ministry of Health, State of Israel | 3-11389 |
Keywords
- Diabetes
- High fat diet
- Metabolic syndrome
- Ventromedial hypothalamus
- Weight cycling
- miRNAs
