Download PDF
Horm Metab Res 2017; 49(11): 880-885
DOI: 10.1055/s-0043-120065
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Lipidomic Changes in Skeletal Muscle in Patients after Biliopancreatic Diversion

Carola Sabine Mehnert   *
1   Department and Outpatient Department of Medicine III, Carl Gustav Carus Medical School, Technische Universitaet Dresden, Dresden, Germany
,
Juergen Graessler   *
1   Department and Outpatient Department of Medicine III, Carl Gustav Carus Medical School, Technische Universitaet Dresden, Dresden, Germany
,
Virginia Kamvissi-Lorenz
1   Department and Outpatient Department of Medicine III, Carl Gustav Carus Medical School, Technische Universitaet Dresden, Dresden, Germany
2   Department of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, Obesity Research Unit, King’s College Hospital London, London, UK
,
Lidia Castagneto Gissey
3   Bariatric and Metabolic Surgery, Division of Diabetes and Nutritional Sciences, King’s College London and King’s College Hospital, London, UK
4   Department of Surgical Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
,
James R. Casella Mariolo
3   Bariatric and Metabolic Surgery, Division of Diabetes and Nutritional Sciences, King’s College London and King’s College Hospital, London, UK
4   Department of Surgical Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
,
Giovanni Casella
4   Department of Surgical Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
,
Geltrude Mingrone
2   Department of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, Obesity Research Unit, King’s College Hospital London, London, UK
5   Department of Internal Medicine, Catholic University, Rome, Italy
,
Stefan R. Bornstein
1   Department and Outpatient Department of Medicine III, Carl Gustav Carus Medical School, Technische Universitaet Dresden, Dresden, Germany
2   Department of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, Obesity Research Unit, King’s College Hospital London, London, UK
› Author Affiliations
Further Information

Publication History

received 05 July 2017

accepted 12 September 2017

Publication Date:
24 October 2017 (online)

Also available at
    Permissions and Reprints

Abstract

The mechanisms behind the fast improvements of insulin sensitivity and release of the diabetic metabolic state after bariatric surgery are still not completely understood. To further elucidate the effects on the individual cellular level, we applied mass spectrometry to investigate the changes in the lipidomic profile of skeletal muscle cells before and after biliopancreatic diversion in six patients. We found a decrease in lipid storage species, mainly triacylglycerides (e. g., TAG 52:2 from 19.84 to 13.26 mol%; p=0.028), and an increase in structural and signaling lipids, including phosphatidylcholines [PC 36:2 (18:1/18:1) from 0.12 to 0.65 mol%; p=0.046], phosphatidylinositols (PI 36:2 from 0.008 to 0.039 mol%; p=0.046), and cardiolipins (CL 72:8 from 0.16 to 1.22 mol%; p=0.043). The proportional increase in structural lipids was directly and the decrease in TAGs was inversely correlated to improved post-operative insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Thus, short-term recovery of insulin sensitivity after biliopancreatic diversion may, beside gut hormonal adaptation, mechanical factors, shifts in the gut microbiome, and changes in bile acid and phospholipid metabolism, additionally be attributed to a metabolic recovery of skeletal muscle cells, reflected by normalization of the cellular lipidomic profile. Further studies are needed to investigate whether improved insulin sensitivity of skeletal muscle might be directly associated with the degradation of ectopic triglycerides, thereby reducing the reservoir of lipotoxic intermediates, which might interfere with insulin signaling and hamper mitochondrial metabolism.

Key words

biliopancreatic diversion - metabolic surgery - lipidomics - skeletal muscle - type-2 diabetes mellitus - insulin sensitivity

* These authors contributed equally to this paper


Supplementary Material

    Supplementary Material for this article is available online at http://www.thieme-connect.de/products
  • Supplementary Material
 

  • References

  • 1 Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 2012; 366: 1577-1585
    CrossrefPubMedGoogle Scholar
  • 2 Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Nanni G, Castagneto M, Bornstein S, Rubino F. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 2015; 386: 964-973
    CrossrefPubMedGoogle Scholar
  • 3 DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 2009; 32 (Suppl. 02) S157-S163
    CrossrefPubMedGoogle Scholar
  • 4 Pan DA, Lillioja S, Milner MR, Kriketos AD, Baur LA, Bogardus C, Storlien LH. Skeletal muscle membrane lipid composition is related to adiposity and insulin action. J Clin Invest 1995; 96: 2802-2808
    CrossrefPubMedGoogle Scholar
  • 5 Bachmann OP, Dahl DB, Brechtel K, Machann J, Haap M, Maier T, Loviscach M, Stumvoll M, Claussen CD, Schick F, Häring HU, Jacob S. Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans. Diabetes 2001; 50: 2579-2584
    CrossrefPubMedGoogle Scholar
  • 6 Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CR, Price 3rd JW, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 2009; 119: 573-581
    CrossrefPubMedGoogle Scholar
  • 7 Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, Xu A, Chavakis T, Bornstein AB, Ehrhart-Bornstein M, Lamounier-Zepter V, Lohmann T, Wolf T, Bornstein SR. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J 2013; 13: 514-522
    CrossrefPubMedGoogle Scholar
  • 8 Graessler J, Bornstein TD, Goel D, Bhalla VP, Lohmann T, Wolf T, Koch M, Qin Y, Licinio J, Wong ML, Chavakis T, Xu A, Shevchenko A, Schuhmann K, Schwarz PE, Schulte KM, Patel A, Bornstein SR. Lipidomic profiling before and after Roux-en-Y gastric bypass in obese patients with diabetes. Pharmacogenomics J 2014; 14: 201-207
    CrossrefPubMedGoogle Scholar
  • 9 DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214-E223
    PubMedGoogle Scholar
  • 10 Sampaio JL, Gerl MJ, Klose C, Ejsing CS, Beug H, Simons K, Shevchenko A. Membrane lipidome of an epithelial cell line. Proc Natl Acad Sci U S A 2011; 108: 1903-1907
    CrossrefPubMedGoogle Scholar
  • 11 Ejsing CS, Sampaio JL, Surendranath V, Duchoslav E, Ekroos K, Klemm RW, Simons K, Shevchenko A. Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc Natl Acad Sci USA 2009; 106: 2136-2141
    CrossrefPubMedGoogle Scholar
  • 12 Herzog R, Schuhmann K, Schwudke D, Sampaio JL, Bornstein SR, Schroeder M, Shevchenko A. LipidXplorer: A software for consensual cross-platform lipidomics. PLoS One 2012; 7: e29851
    CrossrefPubMedGoogle Scholar
  • 13 Stratmann B, Krepak Y, Schiffer E, Jarick I, Hauber M, Lee-Barkey YH, Fischer M, Tschoepe D. Beneficial metabolic effects of duodenal jejunal bypass liner for the treatment of adipose patients with type 2 diabetes mellitus: Analysis of responders and non-responders. Horm Metab Res 2016; 48: 630-637
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Mingrone G, Rosa G, Di Rocco P, Manco M, Capristo E, Castagneto M, Vettor R, Gasbarrini G, Greco AV. Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-alpha reduction and GLUT4 expression enhancement. Int J Obes Relat Metab Disord 2002; 26: 1165-1172
    CrossrefPubMedGoogle Scholar
  • 15 Stratford S, Hoehn KL, Liu F, Summers SA. Regulation of insulin action by ceramide: Dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J. Biol Chem 2004; 279: 36608-36615
    CrossrefPubMedGoogle Scholar
  • 16 Garcia-Ruiz C, Colell A, Mari M, Morales A, Fernández-Checa JC. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. J Biol Chem 1997; 272: 11369-11377
    CrossrefPubMedGoogle Scholar
  • 17 Timmers S, Schrauwen P, de Vogel J. Muscular diacylglycerol and insulin resistance. Physiol Behav. 2008; 94: 242-251
    CrossrefPubMedGoogle Scholar
  • 18 Ho TP, Zhao X, Courville AB, Linderman JD, Smith S, Sebring N, Della Valle DM, Fitzpatrick B, Simchowitz L, Celi FS. Effects of a 12-month moderate weight loss intervention on insulin sensitivity and inflammation status in nondiabetic overweight and obese subjects. Horm Metab Res 2015; 47: 289-296
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Baati N, Feillet-Coudray C, Fouret G, Vernus B, Goustard B, Coudray C, Lecomte J, Blanquet V, Magnol L, Bonnieu A, Koechlin-Ramonatxo C. Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles. Biochim Biophys Acta 2017; 1862: 1044-1055
    CrossrefPubMedGoogle Scholar
  • 20 Sudan R, Jacobs DO. Biliopancreatic diversion with duodenal switch. Surg Clin North Am 2011; 91: 1281-1293
    CrossrefPubMedGoogle Scholar
  • 21 Qi Y, Jiang C, Cheng J, Krausz KW, Li T, Ferrell JM, Gonzalez FJ, Chiang JY. Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice. Biochim Biophys Acta 2015; 1851: 19-29
    CrossrefPubMedGoogle Scholar
  • 22 Kamvissi V, Salerno A, Bornstein SR, Mingrone G, Rubino F. Incretins or anti-incretins? A new model for the “Entero-Pancreatic Axis”. Horm Metab Res 2015; 47: 84-87
    Article in Thieme ConnectPubMedGoogle Scholar