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Int. J. Mol. Sci. 2017, 18(11), 2263; doi:10.3390/ijms18112263

Metformin Potentiates the Benefits of Dietary Restraint: A Metabolomic Study

1
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain
2
Centro de Investigaciones Biológicas (CIB-CSIC), 28040 Madrid, Spain
3
Molecular Oncology Group, Girona Biomedical Research Insitiute (IDIBGI), 17190 Girona, Spain
4
ProCURE (Program against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, 17190 Girona, Spain
5
The Campus of International Excellence Southern Catalonia, 43003 Tarragona, Spain
*
Author to whom correspondence should be addressed.
Received: 12 September 2017 / Revised: 17 October 2017 / Accepted: 25 October 2017 / Published: 28 October 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Prevention of the metabolic consequences of a chronic energy-dense/high-fat diet (HFD) represents a public health priority. Metformin is a strong candidate to be incorporated in alternative therapeutic approaches. We used a targeted metabolomic approach to assess changes related to the multi-faceted metabolic disturbances provoked by HFD. We evaluated the protective effects of metformin and explored how pro-inflammatory and metabolic changes respond when mice rendered obese, glucose-intolerant and hyperlipidemic were switched to diet reversal with or without metformin. Mice treated with metformin and diet-reversal showed a dramatically improved protection against HFD-induced hepatic steatosis, a beneficial effect that was accompanied by a lowering of liver-infiltrating pro-inflammatory macrophages and lower release of pro-inflammatory cytokines. Metformin combined with diet reversal promoted effective weight loss along with better glucose control, lowered levels of circulating cholesterol and triglycerides, and reduced adipose tissue content. Our findings underscored the ability of metformin to target the contribution of branched chain amino acids to adipose tissue metabolism while suppressing mitochondrial-dependent biosynthesis in hepatic tissue. The relationship between adipose tissue and liver might provide clinical potential for combining metformin and dietary modifications to protect against the metabolic damage occurring upon excessive dietary fat intake. View Full-Text
Keywords: adipose tissue; caloric restriction; energy state; inflammation; liver steatosis; metabolomics adipose tissue; caloric restriction; energy state; inflammation; liver steatosis; metabolomics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Riera-Borrull, M.; García-Heredia, A.; Fernández-Arroyo, S.; Hernández-Aguilera, A.; Cabré, N.; Cuyàs, E.; Luciano-Mateo, F.; Camps, J.; Menendez, J.A.; Joven, J. Metformin Potentiates the Benefits of Dietary Restraint: A Metabolomic Study. Int. J. Mol. Sci. 2017, 18, 2263.

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