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Nutrients. 2018 Nov 14;10(11). pii: E1757. doi: 10.3390/nu10111757.

Potential Involvement of Peripheral Leptin/STAT3 Signaling in the Effects of Resveratrol and Its Metabolites on Reducing Body Fat Accumulation.

Author information

1
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain. andrea.ardid@urv.cat.
2
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain. maria.ibars@urv.cat.
3
Department of Food and Drugs, Human Nutrition Unit, University of Parma, 43125 Parma, Italy. pedromiguel.menaparreno@unipr.it.
4
Department of Veterinary Medicine, University of Parma, 43125 Parma, Italy. daniele.delrio@unipr.it.
5
School for Advanced Studies on Food and Nutrition, University of Parma, 43125 Parma, Italy. daniele.delrio@unipr.it.
6
Microbiome Research Hub, University of Parma, 43125 Parma, Italy. daniele.delrio@unipr.it.
7
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain. begona.muguerza@urv.cat.
8
Eurecat, Centre Tecnològic de Catalunya, Unit of Nutrition and Health, 43204 Reus, Spain. begona.muguerza@urv.cat.
9
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain. mariacinta.blade@urv.cat.
10
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain. lluis.arola@urv.cat.
11
Eurecat, Centre Tecnològic de Catalunya, Unit of Nutrition and Health, 43204 Reus, Spain. lluis.arola@urv.cat.
12
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain. gerard.aragones@urv.cat.
13
Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Universitat Rovira i Virgili, 43007 Tarragona, Spain. manuel.suarez@urv.cat.

Abstract

Bioactive compounds such as polyphenols have increased in importance in recent years, and among them, resveratrol (3,5,4'-trihydroxy-trans-stilbene) has generated great interest as an anti-obesity agent. Recent investigations have highlighted the importance of leptin signaling in lipid metabolism in peripheral organs. The aims of this study were (1) to investigate whether resveratrol can reduce fat accumulation in peripheral tissues by increasing their leptin sensitivity and (2) to identify which resveratrol-derived circulating metabolites are potentially involved in these metabolic effects. Serum leptin levels and the leptin signaling pathway were assessed in diet-induced obese rats. Moreover, serum metabolites of resveratrol were studied by ultra-high performance liquid chromatography⁻mass spectrometry (UHPLC-MSn). The daily consumption of 200 mg/kg of resveratrol, but not doses of 50 and 100 mg/kg, reduced body weight and fat accumulation in obese rats and restored leptin sensitivity in the periphery. These effects were due to increases in sirtuin 1 activity in the liver, leptin receptors in muscle and protection against endoplasmic reticulum (ER)-stress in adipose tissue. In general, the resveratrol metabolites associated with these beneficial effects were derived from both phase II and microbiota metabolism, although only those derived from microbiota increased proportionally with the administered dose of resveratrol. In conclusion, resveratrol reversed leptin resistance caused by diet-induced obesity in peripheral organs using tissue-specific mechanisms.

KEYWORDS:

cafeteria diet; leptin resistance; metabolites; microbiota; obesity; sirtuin

PMID:
30441779
PMCID:
PMC6265754
DOI:
10.3390/nu10111757
[Indexed for MEDLINE]
Free PMC Article

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