Abstract
BACKGROUND: The cell functions involved in the action of insulin—receptor binding, enzyme and transporter activities—are controlled by membrane properties. We have previously shown that the fasting plasma insulin (FPI) concentration and the homeostasis model assessment (HOMA) estimate of insulin resistance are associated with the sphingomyelin concentration in the erythrocyte membranes of obese women.
OBJECTIVES: (1) To study the distribution of phospholipid classes in the plasma membrane and their association with insulin resistance markers in the adipocyte, an insulin-sensitive cell in obese women. (2) To investigate the influence of diabetes in a small group of obese women treated by diet alone. (3) To compare the distribution of phospholipids in erythrocyte membranes in a subgroup of obese nondiabetic and diabetic women.
SUBJECTS: Subcutaneous fat biopsies were taken from the abdominal region of 19 obese non-diabetic and seven obese type 2 diabetic women. Erythrocyte membrane assessment was performed in a subgroup of 10 of the 19 obese nondiabetic and in the seven diabetic patients.
METHODS: The phospholipid composition of adipocyte and erythrocyte plasma membranes was analyzed by high performance liquid chromatography.
RESULTS: FPI was positively correlated with the adipocyte membrane contents of sphingomyelin (P<0.001), phosphatidylethanolamine (P<0.05), and phosphatidylcholine (P<0.01) in the obese nondiabetic women. Similar correlations were obtained with HOMA. A stepwise multiple regression analysis indicated that sphingomyelin accounted for 45.6 and 43.8% of the variance in FPI and HOMA values as an independent predictor. There was a similar positive independent association between FPI and SM in the erythrocyte membranes of the studied subgroup. Diabetes per se did not influence the independent association between SM membrane contents and FPI in both cell types.
CONCLUSION: These results suggest a link between membrane phospholipid composition, especially SM, and hyperinsulinemia in obese women.
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References
Devynck MA . Do cell membrane dynamics participate in insulin resistance? Lancet 1995 345: 336–337.
Tong P, Thomas T, Berrish T, Humphriss D, Barriocanal L, Stewart M, Walker M, Wilkinson R, Alberti KG . Cell membrane dynamics and insulin resistance in non-insulin-dependent diabetes mellitus Lancet 1995 345: 357–358.
Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV . The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids New Engl J Med 1993 328: 238–244.
Vessby B, Tenglad S, Lithell H . Insulin sensitivity is related to the fatty acid composition of serum lipids and skeletal muscle phospholipids in 70-year-old men Diabetologia 1994 37: 1044–1050.
Pan DA, Hulbert AJ, Storlien LH . Dietary fats, membrane phospholipids and obesity J Nutr 1994 124: 1555–1565.
Clore JN, Li J, Gill R, Gupta S, Spencer R, Azzam A, Zuelzer W, Rizzo WB, Blackard WG . Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal humans Am J Physiol 1998 275: E665–E670.
Baur LA, O'Connor J, Pan DA, Kriketos AD, Storlien LH . The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children Metabolism 1998 47: 106–112.
Andersson A, Sjödin A, Olsson R, Vessby B . Effects of physical exercise on phospholipid fatty acid composition in skeletal muscle Am J Physiol 1998 274: E432–E438.
Candiloros H, Zeghari N, Ziegler O, Donner M, Drouin P . Hyperinsulinemia is related to erythrocyte phospholipid composition and membrane fluidity changes in obese non diabetic women J Clin Endocrinol Metab 1996 81: 2912–2918.
Després JP, Lemieux S, Lamarche B, Prud'homme D, Moorjani S, Brun LD, Gagné C, Lupien PJ . The insulin resistance-dyslipidemic syndrome: contribution of visceral obesity and therapeutic implications Int J Obes Relat Metab Disord 1995 19 (Suppl 1): S76–S86.
Björntorp P . Fatty acids, hyperinsulinemia, and insulin resistance: which comes first? Curr Opin Lipidol 1994 5: 166–174.
World Health Organization Group on Diabetes Mellitus . Technical report series no. 727 WHO: Geneva 1985.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man Diabetologia 1985 28: 412–419.
Folch J, Lees M, Stanley GH . A simple method for the isolation and purification of total lipids from animal tissues J Biol Chem 1957 226: 497–509.
Stolyhwo A, Martin M . Analysis of lipid classes by HPLC with the evaporative light scattering detector J Liquid Chromatogr 1987 10: 1237–1253.
Khuu Thi-Dinh KL, Demarne Y, Nicolas C, Lhuillery C . Effect of dietary on phospholipid class distribution and fatty acid composition in rat fat cell plasma membrane Lipids 1990 25: 278–283.
Schwertner HA, Mosser EL . Comparison of lipid fatty acids on a concentration basis vs weight percentage basis in patients with and without coronary artery disease or diabetes Clin Chem 1993 39: 659–663.
Guerre-Millo M, Guesnet P, Guichard C, Durand G, Lavau M . Alteration in membrane lipid order and composition in metabolically hyperactive fatty rat adipocytes Lipids 1994 29: 205–209.
Jimenez JG, Fong B, Julien P, Després JP, Rotstein I, Angel A . Effect of massive obesity on low and high density lipoprotein binding to human adipocyte plasma membranes Int J Obes 1989 13: 699–709.
Després JP, Fong BS, Julien P, Jimenez J, Angel A . Regional variation in HDL metabolism in human fat cells: effect of cell size Am J Physiol 1987 252: E654–E659.
Björntorp P, Bengtson C, Blohme G, Jonsson A, Sjöström L, Tibblin E, Tibblin G, Wilhelmsen L . Adipose tissue fat cell size and number in relation to metabolism in randomly selected middle-aged men and women Metabolism 1971 20: 927–935.
Stern M, Olefsky J, Farquhar J, Reaven G . Relationship between fat cell size and insulin resistance in vivo Clin Res 1972 20: 557.
Garvey WT, Birnbaum M . Cellular insulin action and insulin resistance In: Ferrannini E (ed). Bailliere's Clinical Endocrinology and Metabolism: Insulin Resistance and Disease, Vol 7: 1993, pp 785–874.
McCaleb M, Donner DB . Affinity of the hepatic insulin receptor is influenced by membrane phospholipids J Biol Chem 1981 256: 11051–11057.
Sandra A, Fyler DJ, Marshall SJ . Effects of lipids on the transport activity of the reconstituted glucose transport system from rat adipocyte Biochim Biophys Acta 1984 778: 511–515.
Gavrilova NJ, Setchenska MS, Markovska TT, Momchilova-Pankiva AB, Koumanov KS . Effect of membrane phospholipid composition and fluidity on rat liver plasma membrane tyrosine kinase activity Int J Biochem 1993 25: 1309–1312.
Dawson MC, Hemington N, Irvine RF . The inhibition of diacylglycerol-stimulated intracellular phospholipases by phospholipids with a phosphocholine-containing polar group Biochem J 1985 230: 61–68.
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM . Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance J Clin Invest 1995 95: 2409–2415.
Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB . The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase J Clin Invest 1995 95: 2111–2119.
Long SD, Pekala P . Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes Biochem J 1996 319: 179–184.
Brindley DN, Abousalhem A, Kikuchi Y, Wang CN, Waggoner DW . ‘Cross talk’ between the bioactive glycerolipids and sphingolipids in signal transduction Biochem Cell Biol 1996 74: 469–476.
Wang CN, O'Brien L, Brindley DN . Effects of cell-permeable ceramides and tumor necrosis factor-α on insulin signalling and glucose uptake in 3T3-L1 adipocytes Diabetes 1998 47: 24–31.
Kanety H, Hemi R, Papa M, Karasik A . Sphingomyelinase and ceramide suppress insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1 J Biol Chem 1996 271: 9895–9897.
Slater SJ, Kelly MB, Taddeo F, Cojen H, Rubin E, Stubbs CD . The modulation of protein kinase C activity by membrane lipid bilayer structure J Biol Chem 1994 269: 4866–4871.
Egan JJ, Greenberg AS, Chang MK, Wek SA, Moos MC, Londos C . Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet Proc Natl Acad Sci 1992 89: 8537–8541.
Severson DL, Hurley B . Stimulation of hormone sensitive lipase from adipose tissue by phosphatidylethanolamine Biochim Biophys Acta 1985 845: 283–291.
Boden G, Chen X, Ruiz J, White JV, Rosseti L . Mechanisms of fatty acid-induced inhibition of glucose uptake J Clin Invest 1994 93: 2438–2446.
Uchida T . Stimulation of phospholipid synthesis in HeLa cells by epidermal growth factor and insulin: activation of choline kinase and glycerophosphate acyltransferase Biochim Biophys Acta 1996 1304: 89–104.
Kiechle FL, Sykes E, Artiss JD . Insulin and adenosine regulate the phosphatidylcholine concentration in isolated rat adipocyte plasma membranes Ann Clin Lab Sci 1995 25: 310–317.
Taskinen MR . Insulin resistance and lipoprotein metabolism Curr Opin Lipidol 1995 6: 153–160.
Bagdade JD, Buchanan WE, Kuusi T, Taskinen MR . Persistent abnormalities in lipoprotein composition in non-insulin-dependent diabetes after intensive insulin therapy Arteriosclerosis 1990 10: 232–239.
Benoist F, Lau P, McDonnell M, Doelle H, Milne R, McPherson R . Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesterol esters by human adipose tissue J Biol Chem 1997 272: 23572–23577.
Lagrost L, Desrumaux C, Masson D, Deckert V, Gambert P . Structure and function of the plasma phospholipid transfer protein Curr Opin Lipidol 1998 9: 203–209.
Dullaart RPF, Sluiter WJ, Dikkeschi LD, Hoogenberg K, Van Tol A . Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism Eur J Clin Invest 1994 24: 188–194.
Riemens SC, Van Tol A, Sluiter WJ, Dullaart RPF . Plasma phospholipid transfer protein activity is related to insulin resistance: impaired acute lowering by insulin in obese Type II diabetic patients Diabetologia 1998 41: 929–934.
Marra CA, de Alaniz MJT . Regulatory effect of various steroid hormones on the incorporation and metabolism of [14C] stearate in rat hepatoma cells culture Mol Cell Biochem 1995 145: 1–9.
Nelson DH, Murray DK . Dexamethasone increases the synthesis of sphingomyelin in 3T3-L1 cell membranes Proc Natl Acad Sci 1982 79: 6690–6692.
Parish CC, Myher JJ, Kuksis A, Angel A . Lipid structure of rat adipocyte plasma membranes following dietary lard and fish oil Biochim Biophys Acta 1997 1323: 253–262.
Nicolas C, Demarne Y, Lecourtier MJ, Lhuillery CO . Specific alterations in different adipose tissues of pig adipocyte plasma membrane structure by dietary lipids Int J Obes 1990 14: 537–549.
Acknowledgements
This work was in part supported by ALFEDIAM (Grant ALFEDIAM-Institut Servier du Diabète, 1997) and Fondation pour la Recherche Médicale.
We thank Drs Saury and Dinh Doan for their help in performing the biopsies. The English text was corrected by Dr Owen Parkes.
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Zeghari, N., Younsi, M., Meyer, L. et al. Adipocyte and erythrocyte plasma membrane phospholipid composition and hyperinsulinemia: a study in nondiabetic and diabetic obese women. Int J Obes 24, 1600–1607 (2000). https://doi.org/10.1038/sj.ijo.0801459
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DOI: https://doi.org/10.1038/sj.ijo.0801459
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