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Obesity Surgery
Published in: Obesity Surgery 12/2015

01-12-2015 | Original Contributions

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

Authors: Cyrus Jahansouz, Federico J. Serrot, Brigitte I. Frohnert, Rocio E. Foncea, Robert B. Dorman, Bridget Slusarek, Daniel B. Leslie, David A. Bernlohr, Sayeed Ikramuddin

Published in: Obesity Surgery | Issue 12/2015

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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.
Literature
1.
2.
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.PubMedCentralCrossRefPubMed
3.
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.PubMedCentralCrossRefPubMed
4.
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.CrossRefPubMed
5.
6.
De Ferranti S, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008;54(6):945–55.CrossRefPubMed
7.
Abdul-Ghani MA, DeFronzo RA. Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus. Curr Diab Rep. 2008;8(3):173–8.CrossRefPubMed
8.
Viera VJ, Valentine RJ. Mitochondrial biogenesis in adipose tissue: can exercise make fat cells ‘fit’? J Physiol. 2009;587(14):3427–8.CrossRef
9.
Mootha VK, Lindgren CM, Eriksson K, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–73.CrossRefPubMed
10.
Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A. 2003;100(14):8466–71.PubMedCentralCrossRefPubMed
11.
Elizalde M, Rydén M, van Harmelen V, et al. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans. J Lipid Res. 2000;41(8):1244–51.PubMed
12.
Hickner RC, Kemeny G, Stallings HW, et al. Relationship between body composition and skeletal muscle eNOS. Int J Obes. 2006;30(2):308–12.CrossRef
13.
Curtis JM, Grimsrud PA, Wright WS, et al. Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction. Diabetes. 2010;59(5):1132–42.PubMedCentralCrossRefPubMed
14.
Demozay D, Mas J, Rocchi S, et al. FALDH reverses the deleterious action of oxidative stress induced by lipid peroxidation product 4-hydroxynonenal on insulin signaling in 3T3-L1 adipocytes. Diabetes. 2008;57(5):1216–26.CrossRefPubMed
15.
16.
Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006;440(7086):944–8.CrossRefPubMed
17.
Carini M, Aldini G, Facino RM. Mass spectrometry for detection of 4-hydroxy-trans-2-nonenal (HNE) adducts with peptides and proteins. Mass Spectrom Rev. 2004;23(4):281–305.CrossRefPubMed
18.
Grimsrud PA, Picklo MJ, Griffin TJ, et al. Carbonylation of adipose proteins in obesity and insulin resistance: identification of adipocyte fatty acid-binding protein as a cellular target of 4-hydroxynonenal. Mol Cell Proteomics. 2007;6(4):624–37.CrossRefPubMed
19.
Meany DL, Xie H, Thompson LV, et al. Identification of carbonylated proteins from enriched rat skeletal muscle mitochondria using affinity chromatography-stable isotope labeling and tandem mass spectrometry. Proteomics. 2007;7(7):1150–63.CrossRefPubMed
20.
21.
Dahlman I, Forsgren M, Sjogren A, et al. Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-α. Diabetes. 2006;55(6):1792–9.CrossRefPubMed
22.
Valerio A, Cardile A, Cozzi V, et al. TNF-α downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents. J Clin Invest. 2006;116(10):2791–8. Epub 2006 Sep 14.PubMedCentralCrossRefPubMed
23.
Hotamisligil GS, Johnson RS, Distel RJ, et al. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science. 1996;274(5291):1377–9.CrossRefPubMed
24.
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.CrossRefPubMed
25.
Bonora E, Targger G, Alberiche M, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degree of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23:57–63.CrossRefPubMed
26.
Ikramuddin S, Kendrick ML, Kellogg TA, et al. Open and laparoscopic Roux-en-Y gastric bypass: our techniques. J Gastrointest Surg. 2007;11(2):217–28.CrossRefPubMed
27.
Beitner M, Kurian MS. Laparoscopic adjustable gastric banding. Abdom Imaging. 2012.
28.
Frohnert BI, Sinaiko AR, Serrot FJ, et al. Increased adipose protein carbonylation in human obesity. Obesity (Silver Spring). 2011;19(9):1735–41.CrossRef
29.
Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3):248–256.e5.CrossRefPubMed
30.
31.
Wickremesekera K, Miller G, DeSilva Naotunne T, et al. Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obes Surg. 2005;15(4):474–81.CrossRefPubMed
32.
Lima MM, Pareja JC, Alegre SM, et al. Acute effect of roux-en-y gastric bypass on whole-body insulin sensitivity: a study with the euglycemic-hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010;95(8):3871–5.CrossRefPubMed
33.
Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. J Am Med Assoc. 2008;299(3):316–23.CrossRef
34.
Campos GM, Rabl C, Peeva S, et al. Improvement in peripheral glucose uptake after gastric bypass surgery is observed only after substantial weight loss has occurred and correlates with the magnitude of weight lost. J Gastrointest Surg. 2010;14(1):15–23.PubMedCentralCrossRefPubMed
35.
Tammy L, Kindel, Paulo JF, et al. Bypassing the duodenum does not improve insulin resistance associated with diet-induced obesity in rodents. Obesity. 2011;19(2):380–7.CrossRef
36.
Newsholme P, Gaudel C, Krause M. Mitochondria and diabetes. An intriguing pathogenetic role. Adv Exp Med Biol. 2012;942:235–47.CrossRefPubMed
37.
Brands M, Verhoeven AJ, Serlie MJ. Role of mitochondrial function in insulin resistance. Adv Exp Med Biol. 2012;942:215–34.CrossRefPubMed
38.
Martins AR, Nachbar RT, Gorjao R, et al. Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function. Lipids Health Dis. 2012;11:30.PubMedCentralCrossRefPubMed
39.
Pagel-Langenickel I, Bao J, Pang L, et al. The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance. Endocr Rev. 2010;31–1:25–51.CrossRef
40.
Dubé JJ, Amati F, Toledo GS, et al. Effects of weight loss and exercise on insulin resistance and intramyocellular triacylglycerol, diacylglyceroland ceramide. Diabetologia. 2011;54:1147–56.PubMedCentralCrossRefPubMed
41.
Dankel SN, Fadnes DJ, Stavrum AK, et al. Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss. PLoS One. 2010;5–6:e11033.CrossRef
42.
Hernandez-Alvarez MI, Chiellini C, Manco M, et al. Genes involved in mitochondrial biogenesis/function are induced in response to bilio-pancreatic diversion in morbidly obese individuals with normal glucose tolerance but not in type 2 diabetic patients. Diabetologia. 2009;52–8:1618–27.CrossRef
43.
44.
Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444(7121):881–7. Review.CrossRefPubMed
Metadata
Title
Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue
Authors
Cyrus Jahansouz
Federico J. Serrot
Brigitte I. Frohnert
Rocio E. Foncea
Robert B. Dorman
Bridget Slusarek
Daniel B. Leslie
David A. Bernlohr
Sayeed Ikramuddin
Publication date
01-12-2015
Publisher
Springer US
Published in
Obesity Surgery / Issue 12/2015
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-015-1708-5

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