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Time-of-day dependent effect of proanthocyanidins on adipose tissue metabolism in rats with diet-induced obesity

International Journal of Obesity volume 46, pages 1394–1402 (2022)Cite this article

Subjects

Abstract

Background

Grape-seed proanthocyanidin extract (GSPE) improve white adipose tissue (WAT) expansion during diet-induced obesity. However, because adipose metabolism is synchronized by circadian rhythms, it is plausible to speculate that the bioactivity of dietary proanthocyanidins could be influenced by the time-of-day in which they are consumed. Therefore, the aim of the present study was to determine the interaction between zeitgeber time (ZT) and GSPE consumption on the functionality of WAT in rats with diet-induced obesity.

Methods

Male Wistar rats were fed a cafeteria diet for 9 weeks. After 5 weeks, the animals were supplemented with 25 mg GSPE/kg for 4 weeks at the beginning of the light/rest phase (ZT0) or of the dark/active phase (ZT12). Body fat content was determined by nuclear magnetic resonance and histological analyses were performed in the epididymal (EWAT) and inguinal (IWAT) fat depots to determine adipocyte size and number. In addition, the expression of genes related to adipose metabolism and circadian clock function were analyzed by qPCR.

Results

GSPE consumption at ZT0 was associated with a potential antidiabetic effect without affecting adiposity and energy intake and downregulating the gene expression of inflammatory markers in EWAT. In contrast, GSPE consumption at ZT12 improved adipose tissue expansion decreasing adipocyte size in IWAT. In accordance with this adipogenic activity, the expression of genes involved in fatty acid metabolism were downregulated at ZT12 in IWAT. In turn, GSPE consumption at ZT12, but not at ZT0, repressed the expression of the clock gene Cry1 in IWAT.

Conclusions

The interaction between ZT and GSPE consumption influenced the metabolic response of WAT in a tissue-specific manner. Understanding the impact of circadian clock on adipose metabolism and how this is regulated by polyphenols will provide new insights for the management of obesity.

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Fig. 1: Adiposee tissue histology.
Fig. 2: Effects of GSPE on the expression of genes related to adipose metabolism in IWAT.
Fig. 3: Effects of GSPE on the expression of genes related to adipose metabolism in EWAT.
Fig. 4: Effects of GSPE on the expression of clock genes.

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Data availability

Application for datasets generated during and/or analyzed during the current study may be considered by the corresponding author on reasonable request.

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Acknowledgements

We gratefully acknowledge the aid of laboratory technicians Niurka Dariela Llópiz and Rosa Pastor from Universitat Rovira i Virgili.

Funding

This research was supported by a grant (AGL2013-40707-R and AGL2016-77105-R) from the Spanish government. MC-P received a pre-doctoral fellowship from the government of Catalonia (2021 FI_B2 00105). RMR and EN-M received a grant for Ph.D. students from the Universitat Rovira i Virgili (2018PMF-PIPF-11 and 2019PMF-PIPF-73, respectively). GA, MM, and FIB are Serra-Húnter fellows at the Universitat Rovira i Virgili.

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Authors and Affiliations

  1. Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, Nutrigenomics Research Group, Tarragona, Spain

    Marina Colom-Pellicer, Romina M. Rodríguez, Èlia Navarro-Masip, Francisca Isabel Bravo, Miquel Mulero, Lluís Arola & Gerard Aragonès

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  1. Marina Colom-Pellicer
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MC-P, MM, FIB, LA, and GA designed the research; MC-P and RMR performed the experiments and collected the data; MC-P, MM, FIB, LA, and GA analyzed the data and interpreted the results; MC-P, EN-M, and GA wrote the paper. All authors read and approved the final paper.

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Correspondence to Gerard Aragonès.

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Colom-Pellicer, M., Rodríguez, R.M., Navarro-Masip, È. et al. Time-of-day dependent effect of proanthocyanidins on adipose tissue metabolism in rats with diet-induced obesity. Int J Obes 46, 1394–1402 (2022). https://doi.org/10.1038/s41366-022-01132-0

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