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Clinical Studies and Practice

Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery

International Journal of Obesity volume 42, pages 139–146 (2018)Cite this article

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A Correction to this article was published on 06 August 2019

Abstract

Background:

Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined.

Materials and Methods:

Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, β-oxidation, lipolysis and cysteine oxidation.

Results:

Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery.

Conclusions:

These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.

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Acknowledgements

We thank the members of the Bernlohr laboratory, the University of Minnesota Department of Surgery Division of Gastrointestinal and Bariatric Surgery, the University of Minnesota Bionet Department, and the CentraCare Bariatric Center (St. Cloud, MN, USA) for their assistance during the preparation of this manuscript. This study was done using computing resources at the University of Minnesota Supercomputing Institute. This work was supported by the American Diabetes Association (ADA 7-11-ST-01), NIH DK053189 to DAB and the Minnesota Obesity Center (NIH P30DK050456).

Author contributions

CJ, HX, AVH, SI and DAB performed all experiments and data interpretation, and conceived the study design. GL, DBL and SI performed all surgeries and participated in all facets of serum and tissue collection. KE conceived dietary plan and ensured subject compliance. NK, FJS, SSK, HX and CJ collected and stored all specimens. NK, FJS, SSK and CJ performed all qRT–PCR analysis. AVH and HX performed adipose tissue fractionation, western blot, fatty acid oxidation, fatty acid and glycerol measurements. KAS measured cysteine oxidation in SAT. RF and HX measured sera FABP4. CJ, HX, AVH, SSK, SI and DAB wrote the paper.

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Author notes

  1. C Jahansouz and H Xu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, University of Minnesota, Minneapolis, MN, USA

    C Jahansouz, S Kizy, F J Serrot, D B Leslie & S Ikramuddin

  2. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA

    H Xu, A V Hertzel, K A Steen, R Foncea, N Kvalheim & D A Bernlohr

  3. Park Nicollet Bariatric Surgery Center, St. Louis Park, MN, USA

    G Luthra

  4. CentraCare Bariatric Center, St. Cloud, MN, USA

    K Ewing

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  1. C Jahansouz
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Correspondence to S Ikramuddin or D A Bernlohr.

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Jahansouz, C., Xu, H., Hertzel, A. et al. Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery. Int J Obes 42, 139–146 (2018). https://doi.org/10.1038/ijo.2017.197

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