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Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue

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Abstract

Background

Mitochondrial dysfunction in adipose tissue has been implicated as a pathogenic step in the development of type 2 diabetes mellitus (T2DM). In adipose tissue, chronic nutrient overload results in mitochondria driven increased reactive oxygen species (ROS) leading to carbonylation of proteins that impair mitochondrial function and downregulation of key genes linked to mitochondrial biogenesis. In patients with T2DM, Roux-en-Y gastric bypass (RYGB) surgery leads to improvements in glycemic profile prior to significant weight loss. Consequently, we hypothesized that improved glycemia early after RYGB would be paralleled by decreased protein carbonylation and increased expression of genes related to mitochondrial biogenesis in adipose tissue.

Methods

To evaluate this hypothesis, 16 obese individuals were studied before and 7–8 days following RYGB and adjustable gastric banding (AGB). Subcutaneous adipose tissue was obtained pre- and post-bariatric surgery as well as from eight healthy, non-obese individual controls.

Results

Prior to surgery, adipose tissue expression of PGC1α, NRF1, Cyt C, and eNOS (but not Tfam) showed significantly lower expression in the obese bariatric surgery group when compared to lean controls (p < 0.05). Following RYGB, but not after AGB, patients showed significant decrease in HOMA-IR, reduction in adipose protein carbonylation, and increased expression of genes linked to mitochondrial biogenesis.

Conclusions

These results suggest that rapid reduction in protein carbonylation and increased mitochondrial biogenesis may explain postoperative metabolic improvements following RYGB.

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Acknowledgments

This work was supported by the American Diabetes Association (ADA 7-11-ST-01), The Minnesota Obesity Center (NIH DK050456) and NIH DK084669. We thank the members of the Bernlohr laboratory for helpful comments and suggestions during the preparation of this manuscript. We also thank transplant surgeons Drs Ty Dunn, Raja Kandaswamy, Erik B. Finger, David E.R. Sutherland, and Rajinder Singh for their kind assistance in these studies. We declare that the authors do not have any conflict of interests.

Disclosure of Potential Conflict of Interest

Dr. Ikramuddin serves on boards for Novo Nordisk, Medica, and OptumHealth, consults for Metamodix Inc. and Covidien, and has research grants from USGI Medical Inc., Enteromedics, Covidien, and ReShape Medical. Dr. Bernlohr is SAB member for Celladon Corp. For the remaining authors, no conflicts were declared.

Statement of Informed Consent

Informed consent was obtained from all individual participants included in the study.

Statement of Human Rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Source of Funding

The Minnesota Obesity Center (NIH DK050456) and NIH DK084669.

Grant Support

American Diabetes Association (ADA 7-11-ST-01).

Author information

Authors and Affiliations

  1. Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA

    Cyrus Jahansouz, Federico J. Serrot, Robert B. Dorman, Bridget Slusarek, Daniel B. Leslie & Sayeed Ikramuddin

  2. Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA

    Brigitte I. Frohnert

  3. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 420 Delaware St. SE, MMC 195, Minneapolis, MN, 55455, USA

    Rocio E. Foncea & David A. Bernlohr

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  1. Cyrus Jahansouz
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Correspondence to Sayeed Ikramuddin.

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Jahansouz, C., Serrot, F.J., Frohnert, B.I. et al. Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue. OBES SURG 25, 2376–2385 (2015). https://doi.org/10.1007/s11695-015-1708-5

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