Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec;25(12):2376-85.
doi: 10.1007/s11695-015-1708-5.

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

Cyrus Jahansouz  1 , Federico J Serrot  1 , Brigitte I Frohnert  2 , Rocio E Foncea  3 , Robert B Dorman  1 , Bridget Slusarek  1 , Daniel B Leslie  1 , David A Bernlohr  3 , Sayeed Ikramuddin  4
Affiliations

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

Cyrus Jahansouz et al. Obes Surg. 2015 Dec.

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.

Keywords: Adipose tissue; Adjustable gastric banding; Mitochondrial biogenesis; Protein carbonylation; Roux-en-Y gastric bypass.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Relative expression of genes in subcutaneous adipose tissue from lean vs. obese patients. eNOS, NRF1, Tfam, PGC-1α, and Cyt C were significantly reduced in the obese (n=8) group when compared to lean (n=8). Gene expression was normalized to the expression in lean patients (*p<0.05). eNOS endothelial nitric oxide synthase, NRF1 nuclear respiratory factor 1, Tfam mitochondrial transcription factor A, PGC-1α peroxisome proliferator-activated receptor coactivator-1 alpha, Cyt C cytochrome c oxidase
Fig. 2
Fig. 2
Effect of RYGB on relative expression of mitochondrial genes in subcutaneous adipose tissue. eNOS, NRF1, Tfam, PGC-1α, and Cyt C were significantly upregulated 1 week after undergoing RYGB (n=8). Gene expression was normalized to the preoperative expression (*p<0.05). RYGB Roux-en Y gastric bypass, pre Op before surgery, post Op 1 week following surgery, eNOS endothelial nitric oxide synthase, NRF1 nuclear respiratory factor 1, Tfam mitochondrial transcription factor A, PGC-1α peroxisome proliferator-activated receptor coactivator-1 alpha, Cyt C cytochrome c oxidase
Fig. 3
Fig. 3
Effect of laparoscopic AGB on relative expression of mitochondrial genes in subcutaneous adipose tissue. No significant differences were observed in the relative expression of mitochondria-related genes 1 week after undergoing laparoscopic AGB (n=8). Gene expression was normalized to the preoperative expression. AGB adjustable gastric banding, pre Op before surgery, post Op 1 week following surgery, eNOS endothelial nitric oxide synthase, NRF1 nuclear respiratory factor 1, Tfam mitochondrial transcription factor A, PGC-1α peroxisome proliferator-activated receptor coactivator-1 alpha, Cyt C cytochrome c oxidase
Fig. 4
Fig. 4
Protein carbonylation comparison between lean and obese patients. Panel (a) shows a representative blot from one lean to one obese individual where the fatty acid binding protein band is denoted by an arrow. b For each individual, total carbonylation was quantified by analysis of the signal intensity for the entire lane (excluding the 67-kDa albumin band). On average, the obese group (n=5) showed significantly higher carbonylation when compared to the lean cohort of patients (n=5) (*p<0.05). FABP fatty acid binding protein
Fig. 5
Fig. 5
Protein carbonylation before and 1 week after RYGB. Panel (a) shows a representative blot from one obese individual before and 1 week following RYGB operation. An arrow denotes fatty acid binding protein band. b For each individual, total carbonylation was quantified by analysis of the signal intensity for the entire lane (excluding the 67-kDa albumin band). On average, there was a significant reduction in protein carbonylation 1 week after undergoing RYGB on five patients with T2DM (*p<0.05). FABP fatty acid binding protein, RYGB roux-en Y gastric bypass, T2DM type 2 diabetes mellitus
Fig. 6
Fig. 6
Protein carbonylation before and 1 week after AGB. Panel (a) shows a representative blot from one obese individual before and 1 week following AGB operation. An arrow denotes fatty acid binding protein band. b For each individual, total carbonylation was quantified by analysis of the signal intensity for the entire lane (excluding the 67-kDa albumin band). There were no changes in protein carbonylation 1 week following AGB on three patients with T2DM. FABP fatty acid binding protein, AGB adjustable gastric banding, T2DM type 2 diabetes mellitus
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ikramuddin S, Korner J, Lee WJ, et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial. JAMA. 2013;309(21):2240–9. doi:10.1001/jama.2013.5835. - PMC - PubMed
    1. Isbell JM, Tamboli RA, Hansen EN, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. 2010;33(7):1438–42. Epub 2010 Apr 5. - PMC - PubMed
    1. Dunn JP, Abumurad NN, Breitman I, et al. Hepatic and peripheral insulin sensitivity and diabetes remission at 1 month after Roux-en-Y gastric bypass surgery in patients randomized to omentectomy. Diabetes Care. 2012;35:137–42. - PMC - PubMed
    1. Malandrucco I, Pasqualetti P, Giordani I, et al. Very-low-calorie diet: a quick therapeutic tool to improve b cell function in morbidly obese patients with type 2 diabetes. Am J Clin Nutr. 2012;95:609–13. - PubMed
    1. Boudina S, Graham TE. Mitochondrial function/dysfunction in white adipose tissue. Exp Physiol. 2014;99(9):1168–78. doi:10.1113/expphysiol.2014.081414. Epub 2014 Aug 15. - PubMed

Publication types

MeSH terms

Substances