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Int J Obes (Lond). 2018 Apr;42(4):728-736. doi: 10.1038/ijo.2017.266. Epub 2017 Nov 1.

Obesity-induced changes in lipid mediators persist after weight loss.

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Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, CA, USA.
Department of Nutrition, University of California, Davis, CA, USA.
NIH West Coast Metabolomics Center, Davis, CA, USA.
Department of Food Science and Nutrition, California Polytechnic State University, San Luis Obispo, CA, USA.
The Wallenberg Laboratory for Cardiovascular and Metabolic Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Obesity and Metabolism Research Unit, USDA-ARS-Western Human Nutrition Research Center, Davis, CA, USA.



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


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.


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.


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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