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Bariatric surgery alters mitochondrial function in gut mucosa

  • 2023 SAGES Oral
  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria—a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS.

Methods

Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5 mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content.

Results

Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups.

Conclusion

Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes.

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References

  1. Ciciurkaite G, Moloney ME, Brown RL (2019) The incomplete medicalization of obesity: physician office visits, diagnoses, and treatments, 1996–2014. Public Health Rep 134:141–149. https://doi.org/10.1177/0033354918813102

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hales CM, Carroll MD, Fryar CD, Ogden CL (2020) Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief 1–8

  3. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, Navaneethan SD, Singh RP, Pothier CE, Nissen SE, Kashyap SR, Investigators S (2017) Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. New Engl J Med 376:641–651. https://doi.org/10.1056/nejmoa1600869

    Article  PubMed  Google Scholar 

  4. Steenackers N, Vanuytsel T, Augustijns P, Tack J, Mertens A, Lannoo M, der Schueren BV, Matthys C (2021) Adaptations in gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass. Lancet Gastroenterol Hepatol 6:225–237. https://doi.org/10.1016/s2468-1253(20)30302-2

    Article  Google Scholar 

  5. Akalestou E, Miras AD, Rutter GA, le Roux CW (2021) Mechanisms of weight loss after obesity surgery. Endocr Rev 43:bnab22. https://doi.org/10.1210/endrev/bnab022

    Article  Google Scholar 

  6. Clapp B, Ponce J, DeMaria E, Ghanem O, Hutter M, Kothari S, LaMasters T, Kurian M, English W (2022) American society for metabolic and bariatric surgery 2020 estimate of metabolic and bariatric procedures performed in the United States. Surg Obes Relat Dis 18:1134–1140. https://doi.org/10.1016/j.soard.2022.06.284

    Article  PubMed  Google Scholar 

  7. Steenackers N, Vanuytsel T, Augustijns P, Deleus E, Deckers W, Deroose CM, Falony G, Lannoo M, Mertens A, Mols R, Vangoitsenhoven R, Wauters L, der Schueren BV, Matthys C (2023) Effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal physiology. Eur J Pharm Biopharm 183:92–101. https://doi.org/10.1016/j.ejpb.2022.12.018

    Article  Google Scholar 

  8. Seeley RJ, Chambers AP, Sandoval DA (2015) The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes. Cell Metab 21:369–378. https://doi.org/10.1016/j.cmet.2015.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Williams JM, Duckworth CA, Burkitt MD, Watson AJM, Campbell BJ, Pritchard DM (2015) Epithelial cell shedding and barrier function. Vet Pathol 52:445–455. https://doi.org/10.1177/0300985814559404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mulla CM, Middelbeek RJW, Patti M (2018) Mechanisms of weight loss and improved metabolism following bariatric surgery. Ann NY Acad Sci 1411:53–64. https://doi.org/10.1111/nyas.13409

    Article  PubMed  Google Scholar 

  11. Lahera V, de las Heras N, López-Farré A, Manucha W, Ferder L (2017) Role of mitochondrial dysfunction in hypertension and obesity. Curr Hypertens Rep 19:11. https://doi.org/10.1007/s11906-017-0710-9

    Article  CAS  PubMed  Google Scholar 

  12. Boengler K, Kosiol M, Mayr M, Schulz R, Rohrbach S (2017) Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle 8:349–369. https://doi.org/10.1002/jcsm.12178

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cao K, Xu J, Zou X, Li Y, Chen C, Zheng A, Li H, Li H, Szeto IM-Y, Shi Y, Long J, Liu J, Feng Z (2014) Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice. Free Radical Bio Med 67:396–407. https://doi.org/10.1016/j.freeradbiomed.2013.11.029

    Article  CAS  Google Scholar 

  14. Sergi D, Naumovski N, Heilbronn LK, Abeywardena M, O’Callaghan N, Lionetti L, Luscombe-Marsh N (2019) Mitochondrial (Dys)function and insulin resistance: from pathophysiological molecular mechanisms to the impact of diet. Front Physiol 10:532. https://doi.org/10.3389/fphys.2019.00532

    Article  PubMed  PubMed Central  Google Scholar 

  15. Guerbette T, Boudry G, Lan A (2022) Mitochondrial function in intestinal epithelium homeostasis and modulation in diet-induced obesity. Mol Metab 63:101546. https://doi.org/10.1016/j.molmet.2022.101546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieuwoudt S, Fitzgerald K, Pergola K, Fujioka H, Mey JT, Fealy C, Mulya A, Beyl R, Hoppel CL, Kirwan JP (2020) BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. Embo Mol Med 12:e12088. https://doi.org/10.15252/emmm.202012088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zunica ERM, Axelrod CL, Gilmore LA, Kirwan JP (2021) Analytical determination of mitochondrial function of excised solid tumor homogenates. J Vis Exp. https://doi.org/10.3791/62875

    Article  PubMed  Google Scholar 

  18. Larsen S, Nielsen J, Hansen CN, Nielsen LB, Wibrand F, Stride N, Schroder HD, Boushel R, Helge JW, Dela F, Hey-Mogensen M (2012) Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol 590:3349–3360. https://doi.org/10.1113/jphysiol.2012.230185

    Article  CAS  Google Scholar 

  19. Strader AD, Vahl TP, Jandacek RJ, Woods SC, D’Alessio DA, Seeley RJ (2005) Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol-endocrinol M 288:E447–E453. https://doi.org/10.1152/ajpendo.00153.2004

    Article  CAS  Google Scholar 

  20. Culnan DM, Albaugh V, Sun M, Lynch CJ, Lang CH, Cooney RN (2010) Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat. Am J Physiol-gastrointest L 299:G751–G760. https://doi.org/10.1152/ajpgi.00525.2009

    Article  CAS  Google Scholar 

  21. Kohli R, Kirby M, Setchell KDR, Jha P, Klustaitis K, Woollett LA, Pfluger PT, Balistreri WF, Tso P, Jandacek RJ, Woods SC, Heubi JE, Tschoep MH, D’Alessio DA, Shroyer NF, Seeley RJ (2010) Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol 299:G652–G660. https://doi.org/10.1152/ajpgi.00221.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nath S (2019) Integration of demand and supply sides in the ATP energy economics of cells. Biophys Chem 252:106208. https://doi.org/10.1016/j.bpc.2019.106208

    Article  CAS  PubMed  Google Scholar 

  23. Houten SM, Violante S, Ventura FV, Wanders RJA (2015) The biochemistry and physiology of mitochondrial fatty acid β-oxidation and its genetic disorders. Annu Rev Physiol 78:1–22. https://doi.org/10.1146/annurev-physiol-021115-105045

    Article  CAS  Google Scholar 

  24. Sarparanta J, García-Macia M, Singh R (2017) Autophagy and mitochondria in obesity and type 2 diabetes. Curr Diabetes Rev 13:352–369. https://doi.org/10.2174/1573399812666160217122530

    Article  CAS  PubMed  Google Scholar 

  25. Dantas WS, Zunica ERM, Heintz EC, Vandanmagsar B, Floyd ZE, Yu Y, Fujioka H, Hoppel CL, Belmont KP, Axelrod CL, Kirwan JP (2022) Mitochondrial uncoupling attenuates sarcopenic obesity by enhancing skeletal muscle mitophagy and quality control. J Cachexia Sarcopenia Muscle 13:1821–1836. https://doi.org/10.1002/jcsm.12982

    Article  PubMed Central  Google Scholar 

  26. Franquet E, Watts G, Kolodny GM, Goldfine AB, Patti M-E (2019) PET-CT reveals increased intestinal glucose uptake after gastric surgery. Surg Obes Relat Dis 15:643–649. https://doi.org/10.1016/j.soard.2019.01.018

    Article  PubMed  PubMed Central  Google Scholar 

  27. Cho A, Kwon IG, Kim S, Noh SH, Ku CR (2020) Altered systematic glucose utilization after gastrectomy: correlation with weight loss. Surg Obes Relat Dis 16:900–907. https://doi.org/10.1016/j.soard.2020.03.003

    Article  PubMed  Google Scholar 

  28. Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N (2013) Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science 341:406–410. https://doi.org/10.1126/science.1235103

    Article  CAS  PubMed Central  Google Scholar 

  29. Koopmans H, Sclafani A, Fichtner C, Aravich P (1982) The effects of ileal transposition on food intake and body weight loss in VMH-obese rats. Am J Clin Nutr 35:284–293. https://doi.org/10.1093/ajcn/35.2.284

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank the staff of the Comparative Biology Core facility at Pennington Biomedical Research Center for exceptional animal care.

Funding

The research presented in this manuscript was in part supported by NIH Grants U54GM104940 and T32 AT004094 and received no additional specific funding from any agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Translational & Integrative Gastrointestinal & Endocrine Research (TIGER) Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd, Baton Rouge, LA, USA

    Robert C. Ross, R. Leigh Townsend, Amanda E. Spence & Vance L. Albaugh

  2. Integrated Physiology & Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA

    Elizabeth C. Heintz, Elizabeth R. M. Zunica, John P. Kirwan & Christopher L. Axelrod

  3. Pennington Biomedical Research Center, Metamor Institute, Louisiana State University, Baton Rouge, LA, USA

    Philip R. Schauer & Vance L. Albaugh

  4. Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Philip R. Schauer & Vance L. Albaugh

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  1. Robert C. Ross
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Correspondence to Vance L. Albaugh.

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Disclosures

Dr. Elizabeth Zunica receives support from the National Institute of Health grant T32AT004094; Dr. Philip Schauer receives support via institutional grants from Ethicon and Medtronic, consulting fees from GI Dynamics, Mediflix, and Persona, speaker fees from Ethicon, Medtronic, Lilly, and Novo Nordisk, and has equity in SE Healthcare LLC, Mediflix, and Metabolic Health International LTD. Dr. Robert C. Ross, Elizabeth Heintz, R. Leigh Townsend, Amanda Spence, Dr. John P. Kirwan, Christopher L. Axelrod, and Dr. Vance L. Albaugh have no financial relationships with any pharmaceutical or device company.

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Ross, R.C., Heintz, E.C., Zunica, E.R.M. et al. Bariatric surgery alters mitochondrial function in gut mucosa. Surg Endosc 37, 8810–8817 (2023). https://doi.org/10.1007/s00464-023-10351-z

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