Skip to main content

Advertisement

SpringerLink
Log in

Estimated Elovl6 and delta-5 desaturase activities might represent potential markers for insulin resistance in Japanese adults

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Purpose

Results from a recent study indicated that lower stearic acid/palmitic acid (SA/PA) and arachidonic acid/dihomo-γ-linolenic acid (AA/DGLA) ratios were associated with metabolically unhealthy obesity. However, this has not been extensively studied in the Japanese population.

Methods

We recruited 291 Japanese subjects with serum free fatty acid profiles undergoing health examinations. Whole serum desaturase activity was estimated as the product: precursor ratio –SA/PA ratio for elongation of long-chain fatty acid family member 6 (Elovl6) and AA/DGLA for delta-5 desaturase (D5D). The determinants of Elovl6 and D5D activity were investigated using multiple regression analyses.

Results

The Elovl6 and D5D activities exhibited a negative correlation with the logmatic-transformed TG/HDL-C ratio and TyG index. Multiple regression analyses revealed that the TG/HDL-C ratio and TyG index were negatively associated with Elovl6 and D5D activities. Most atherogenic markers were worse in the low Elovl6 or D5D activity group than in the high Elovl6 or D5D activity group. When study subjects were further stratified by TG levels, most atherogenic markers were the worst in the highest TG group in either the lowest Elovl6 or lowest D5D activity groups.

Conclusion

The estimated Elovl6 and D5D activities might be useful markers of insulin resistance in Japanese subjects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pankow JS, Duncan BB, Schmidt MI, Ballantyne CM, Couper DJ, Hoogeveen RC, et al. Atherosclerosis Risk in Communities Study. Fasting plasma free fatty acids and risk of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes Care. 2004;27:77–82.

  2. Charles MA, Eschwège E, Thibult N, Claude JR, Warnet JM, Rosselin GE, et al. The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: results of the Paris Prospective Study. Diabetologia. 1997;40:1101–6.

    Article  CAS  PubMed  Google Scholar 

  3. Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia. 1995;38:1213–7.

    Article  CAS  PubMed  Google Scholar 

  4. Boden G. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes. 2003;111:121–4.

    Article  CAS  PubMed  Google Scholar 

  5. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Invest. 2002;32:14–23.

    Article  CAS  PubMed  Google Scholar 

  6. Boden G. Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes. 2011;18:139–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yary T, Voutilainen S, Tuomainen TP, Ruusunen A, Nurmi T, Virtanen JK. Serum n-6 polyunsaturated fatty acids, Δ5- and Δ6-desaturase activities, and risk of incident type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr. 2016;103:1337–43.

    Article  CAS  PubMed  Google Scholar 

  8. Tsurutani Y, Inoue K, Sugisawa C, Saito J, Omura M, Nishikawa T. Increased Serum Dihomo-γ-linolenic Acid Levels Are Associated with Obesity, Body Fat Accumulation, and Insulin Resistance in Japanese Patients with Type 2 Diabetes. Intern Med. 2018;57:2929–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hodson L, Skeaff CM, Fielding BA. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res. 2008;47:348–80.

    Article  CAS  PubMed  Google Scholar 

  10. Lankinen MA, Stančáková A, Uusitupa M, Ågren J, Pihlajamäki J, Kuusisto J, et al. Plasma fatty acids as predictors of glycaemia and type 2 diabetes. Diabetologia. 2015;58:2533–44.

    Article  CAS  PubMed  Google Scholar 

  11. Jacobs S, Schiller K, Jansen EH, Boeing H, Schulze MB, Kröger J. Evaluation of various biomarkers as potential mediators of the association between D5 desaturase, D6 desaturase, and stearoyl-CoA desaturase activity and incident type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. Am J Clin Nutr. 2015;102:155–64.

    Article  CAS  PubMed  Google Scholar 

  12. Mahendran Y, Ågren J, Uusitupa M, Cederberg H, Vangipurapu J, Stančáková A, et al. Association of erythrocyte membrane fatty acids with changes in glycemia and risk of type 2 diabetes. Am J Clin Nutr. 2014;99:79–85.

    Article  CAS  PubMed  Google Scholar 

  13. Patel PS, Sharp SJ, Jansen E, Luben RN, Khaw KT, Wareham NJ, et al. Fatty acids measured in plasma and erythrocyte membrane phospholipids and derived by food-frequency questionnaire and the risk of new-onset type 2 diabetes: a pilot study in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk cohort. Am J Clin Nutr. 2010;92:1214–22.

    Article  CAS  PubMed  Google Scholar 

  14. Corpeleijn E, Feskens EJ, Jansen EH, Mensink M, Saris WH, de Bruin TW, et al. Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities: the SLIM study. Diabetologia. 2006;49:2392–401.

    Article  CAS  PubMed  Google Scholar 

  15. Hodge AM, English DR, O’Dea K, Sinclair AJ, Makrides M, Gibson RA, et al. Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid. Am J Clin Nutr. 2007;86:189–97.

    Article  CAS  PubMed  Google Scholar 

  16. van Woudenbergh GJ, Kuijsten A, Van der Kallen CJ, Van Greevenbroek MM, Stehouwer CD, Blaak EE, et al. Comparison of fatty acid proportions in serum cholesteryl esters among people with different glucose tolerance status: the CoDAM study. Nutr Metab Cardiovasc Dis. 2012;22:133–40.

    Article  PubMed  Google Scholar 

  17. Warensjo E, Rosell M, Hellenius ML, Vessby B, De Faire U, Riserus U. Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance. Lipids Health Dis. 2009;8:37.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zhao L, Ni Y, Ma X, Zhao A, Bao Y, Liu J, et al. A panel of free fatty acid ratios to predict the development of metabolic abnormalities in healthy obese individuals. Sci Rep. 2016;6:28418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Moriyama K, Kishimoto N, Shiina Y, Urata N, Masuda Y, Oda K, et al. Oleic to stearic acid ratio might be a potential marker for insulin resistance in non-obese Japanese. J Clin Biochem Nutr. 2021;68:164–8.

    Article  CAS  PubMed  Google Scholar 

  20. Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord. 2008;6:299–304.

    Article  PubMed  Google Scholar 

  21. Guerrero-Romero F, Simental-Mendía LE, González-Ortiz M, Martínez-Abundis E, Ramos-Zavala MG, Hernández-González SO, et al. The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010;95:3347–51.

  22. Shimano H. SREBPs: physiology and pathophysiology of the SREBP family. FEBS J. 2009;276:616–21.

    Article  CAS  PubMed  Google Scholar 

  23. Matsuzaka T, Shimano H, Yahagi N, Kato T, Atsumi A, Yamamoto T, et al. Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat Med. 2007;13:1193–202.

    Article  CAS  PubMed  Google Scholar 

  24. Matsuzaka T, Atsumi A, Matsumori R, Nie T, Shinozaki H, Suzuki-Kemuriyama N, et al. Elovl6 promotes nonalcoholic steatohepatitis. Hepatology. 2012;56:2199–208.

    Article  CAS  PubMed  Google Scholar 

  25. Moon YA, Ochoa CR, Mitsche MA, Hammer RE, Horton JD. Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance. J Lipid Res. 2014;55:2597–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shimamura K, Nagumo A, Miyamoto Y, Kitazawa H, Kanesaka M, Yoshimoto R, et al. Discovery and characterization of a novel potent, selective and orally active inhibitor for mammalian ELOVL6. Eur J Pharmacol. 2010;630:34–41.

    Article  CAS  PubMed  Google Scholar 

  27. Green CD, Olson LK. Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic beta-cells by stearoyl-CoA desaturase and Elovl6. Am J Physiol Endocrinol Metab. 2011;300:E640–9.

    Article  CAS  PubMed  Google Scholar 

  28. Beccarelli LM, Scherr RE, Newman JW, Borkowska AG, Gray IJ, Linnell JD, et al. Associations Among Fatty Acids, Desaturase and Elongase, and Insulin Resistance in Children. J Am Coll Nutr. 2018;37:44–50.

    Article  CAS  PubMed  Google Scholar 

  29. Jacobs S, Schiller K, Jansen E, Fritsche A, Weikert C, di Giuseppe R, et al. Association between erythrocyte membrane fatty acids and biomarkers of dyslipidemia in the EPIC-Potsdam study. Eur J Clin Nutr. 2014;68:517–25.

    Article  CAS  PubMed  Google Scholar 

  30. Do HJ, Chung HK, Moon J, Shin MJ. Relationship between the estimates of desaturase activities and cardiometabolic phenotypes in Koreans. J Clin Biochem Nutr. 2011;49:131–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kim SR, Jeon SY, Lee SM. The association of cardiovascular risk factors with saturated fatty acids and fatty acid desaturase indices in erythrocyte in middle-aged Korean adults. Lipids Health Dis. 2015;14:133.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Laaksonen DE, Lakka TA, Lakka HM, Nyyssönen K, Rissanen T, Niskanen LK, et al. Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle-aged men. Diabet Med. 2002;19:456–64.

    Article  CAS  PubMed  Google Scholar 

  33. Warensjö E, Rosell M, Hellenius ML, Vessby B, De Faire U, Risérus U. Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance. Lipids Health Dis. 2009;8:37.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Warensjö E, Risérus U, Vessby B. Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men. Diabetologia. 2005;48:1999–2005.

    Article  PubMed  Google Scholar 

  35. Kawashima A, Sugawara S, Okita M, Akahane T, Fukui K, Hashiuchi M, et al. Plasma fatty acid composition, estimated desaturase activities, and intakes of energy and nutrient in Japanese men with abdominal obesity or metabolic syndrome. J Nutr Sci Vitaminol (Tokyo). 2009;55:400–6.

    Article  CAS  Google Scholar 

  36. Murakami K, Sasaki S, Takahashi Y, Uenishi K, Watanabe T, Kohri T, et al. Lower estimates of delta-5 desaturase and elongase activity are related to adverse profiles for several metabolic risk factors in young Japanese women. Nutr Res. 2008;28:816–24.

    Article  CAS  PubMed  Google Scholar 

  37. Kroger J, Schulze MB. Recent insights into the relation of delta5 desaturase and delta6 desaturase activity to the development of type 2 diabetes. Curr Opin Lipidol. 2012;23:4–10.

    Article  PubMed  Google Scholar 

  38. Tsurutani Y, Inoue K, Sugisawa C, Saito J, Omura M, Nishikawa T. Increased Serum Dihomo-gamma-linolenic Acid Levels Are Associated with Obesity, Body Fat Accumulation, and Insulin Resistance in Japanese Patients with Type 2 Diabetes. Intern Med. 2018;57:2929–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Araya J, Rodrigo R, Pettinelli P, Araya AV, Poniachik J, Videla LA. Decreased liver fatty acid delta-6 and delta-5 desaturase activity in obese patients. Obesity (Silver Spring). 2010;18:1460–3.

    Article  CAS  Google Scholar 

  40. Poudel-Tandukar K, Sato M, Ejima Y, Nanri A, Matsushita Y, Imaizumi K, et al. Relationship of serum fatty acid composition and desaturase activity to C-reactive protein in Japanese men and women. Atherosclerosis. 2012;220:520–4.

    Article  CAS  PubMed  Google Scholar 

  41. Devaraj S, Singh U, Jialal I. Human C-reactive protein and the metabolic syndrome. Curr Opin Lipidol. 2009;20:182–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gromovsky AD, Schugar RC, Brown AL, Helsley RN, Burrows AC, Ferguson D, et al. Δ-5 Fatty Acid Desaturase FADS1 Impacts Metabolic Disease by Balancing Proinflammatory and Proresolving Lipid Mediators. Arterioscler Thromb Vasc Biol. 2018;38:218–31.

    Article  CAS  PubMed  Google Scholar 

  43. Marques-Lopes I, Ansorena D, Astiasaran I, Forga L, Martínez JA. Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men. Am J Clin Nutr. 2001;73:253–61.

    Article  CAS  PubMed  Google Scholar 

  44. Wilke MS, French MA, Goh YK, Ryan EA, Jones PJ, Clandinin MT. Synthesis of specific fatty acids contributes to VLDL-triacylglycerol composition in humans with and without type 2 diabetes. Diabetologia. 2009;52:1628–37.

    Article  CAS  PubMed  Google Scholar 

  45. Takkunen MJ, Schwab US, de Mello VD, Eriksson JG, Lindström J, Tuomilehto J, et al. DPS Study Group. Longitudinal associations of serum fatty acid composition with type 2 diabetes risk and markers of insulin secretion and sensitivity in the Finnish Diabetes Prevention Study. Eur J Nutr. 2016;55:967–79.

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Health Science, Tokai University School of Medicine, Tokai University Hachioji Hospital, 1838 Ishikawa-machi, Hachioji, Tokyo, 192-0032, Japan

    Kengo Moriyama

  2. Department of Clinical Health Science, Tokai University School of Medicine, 1-2-5, Yoyogi, Tokyo, 151-0053, Japan

    Yumi Masuda, Chizumi Yamada, Noriaki Kishimoto, Akira Kubo & Yasuhiro Nishizaki

  3. Department of Clinical Health Science, Tokai University School of Medicine, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Nana Suzuki & Shinji Takashimizu

  4. Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Tokyo, 151-0053, Japan

    Chizumi Yamada, Noriaki Kishimoto, Akira Kubo & Yasuhiro Nishizaki

Authors
  1. Kengo Moriyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yumi Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nana Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chizumi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noriaki Kishimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shinji Takashimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akira Kubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yasuhiro Nishizaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kengo Moriyama.

Ethics declarations

Ethics approval and consent to participate

All subjects provided written informed consent for the use of their health records for analysis. This study was approved by the Ethics Committee of Tokai University (No. 11R-125) and was conducted in accordance with the Declaration of Helsinki.

Conflict of interest

There are no conflicts of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moriyama, K., Masuda, Y., Suzuki, N. et al. Estimated Elovl6 and delta-5 desaturase activities might represent potential markers for insulin resistance in Japanese adults. J Diabetes Metab Disord 21, 197–207 (2022). https://doi.org/10.1007/s40200-021-00958-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-021-00958-1

Keywords

Search

Navigation