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Obesity-induced changes in lipid mediators persist after weight loss

International Journal of Obesity volume 42, pages 728–736 (2018)Cite this article

Subjects

Abstract

Background:

Obesity induces significant changes in lipid mediators, however, the extent to which these changes persist after weight loss has not been investigated.

Subjects/Methods:

We fed C57BL6 mice a high-fat diet to generate obesity and then switched the diet to a lower-fat diet to induce weight loss. We performed a comprehensive metabolic profiling of lipid mediators including oxylipins, endocannabinoids, sphingosines and ceramides in key metabolic tissues (including adipose, liver, muscle and hypothalamus) and plasma.

Results:

We found that changes induced by obesity were largely reversible in most metabolic tissues but the adipose tissue retained a persistent obese metabolic signature. Prostaglandin signaling was perturbed in the obese state and lasting increases in PGD2, and downstream metabolites 15-deoxy PGJ2 and delta-12-PGJ2 were observed after weight loss. Furthermore expression of the enzyme responsible for PGD2 synthesis (hematopoietic prostaglandin D synthase, HPGDS) was increased in obese adipose tissues and remained high after weight loss. We found that inhibition of HPGDS over the course of 5 days resulted in decreased food intake in mice. Increased HPGDS expression was also observed in human adipose tissues obtained from obese compared with lean individuals. We then measured circulating levels of PGD2 in obese patients before and after weight loss and found that while elevated relative to lean subjects, levels of this metabolite did not decrease after significant weight loss.

Conclusions:

These results suggest that lasting changes in lipid mediators induced by obesity, still present after weight loss, may play a role in the biological drive to regain weight.

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Acknowledgements

This study was supported by UCSD/UCLA NIDDK Diabetes Research Center P30 DK063491 (OO) and a Pilot and Feasibility grant (OO) from the UC Davis NIH West Coast Metabolomics Center U24 DK097154. Angelina Hernandez-Carretero is an IRACDA fellow and was supported by NIGMS/NIH award K12GM068524. Additional funding was provided by USDA intramural project #2032-51530-022-00D (JWN). EB is supported by the Swedish Research Council (no. 2016/82), the Swedish Society for Medical Research (no. S150086), Åke Wiberg’s Foundation (no. M15-0058), Knut & Alice Wallenberg Foundation, Wallenberg Centre for Molecular & Translational Medicine, University of Gothenburg, Sweden. VW reports grants from Western Region of Sweden; ALFGBG-542701, grants from Erik and Lily Philipson memorial foundation, during the conduct of the study; personal fees from Johnson & Johnson, outside the submitted work. The USDA is an equal opportunity provider and employer. We thank Johannes Fahrmann for his contribution to the statistical analysis.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA

    A Hernandez-Carretero, N Weber, W Ying, D D Sears & O Osborn

  2. Department of Nutrition, University of California, Davis, CA, USA

    M R La Frano & J W Newman

  3. NIH West Coast Metabolomics Center, Davis, CA, USA

    M R La Frano & J W Newman

  4. Department of Food Science and Nutrition, California Polytechnic State University, San Luis Obispo, CA, USA

    M R La Frano

  5. The Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    J Lantero Rodriguez & E Börgeson

  6. Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    V Wallenius

  7. Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden

    E Börgeson

  8. Obesity and Metabolism Research Unit, USDA-ARS-Western Human Nutrition Research Center, Davis, CA, USA

    J W Newman

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  1. A Hernandez-Carretero
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Correspondence to O Osborn.

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Hernandez-Carretero, A., Weber, N., La Frano, M. et al. Obesity-induced changes in lipid mediators persist after weight loss. Int J Obes 42, 728–736 (2018). https://doi.org/10.1038/ijo.2017.266

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