Skip to main content

Advertisement

Log in

Dietary interventions for metabolic syndrome: Role of modifying dietary fats

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

In humans, insulin sensitivity is relatively impaired by diets that are low in oleic acid (OA), a cis monounsaturated fatty acid (MUFA), or rich in trans MUFA or palmitic acid (PA), a saturated fatty acid (FA). Emerging evidence exists that PA, in contrast to OA, causes insulin resistance via stimulation of inflammatory signaling and production of cytosolic lipid compounds (diacylglycerol and ceramide), leading one to presume that dietary or pharmacologic maneuvers that facilitate transport of FA into the mitochondria would be beneficial. However, in some models, insulin resistance is caused by excessive FA transport into the mitochondria, coupled with deficient electron transport and possibly increased reactive oxygen species formation; PA may impair electron transport via effects on gene expression. A research challenge is to determine whether feeding humans diets with markedly different contents of PA and OA would alter insulin sensitivity and/or critical biochemical mechanisms impacting muscle insulin signaling.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Muoio DM, Newgard CB: Obesity-related derangements in metabolic regulation. Annu Rev Biochem 2006, 75:367–401.

    Article  PubMed  CAS  Google Scholar 

  2. Tardy AL, Giraudet C, Rousset P, et al.: Effects of trans MUFA from dairy and industrial sources on muscle mitochondrial function and insulin sensitivity. J Lipid Res 2008, 49:1445–1455.

    Article  PubMed  CAS  Google Scholar 

  3. Riserus U, Arner P, Brismar K, Vessby B: Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 2002, 25:1516–1521.

    Article  PubMed  CAS  Google Scholar 

  4. Dimopoulos N, Watson M, Sakamoto K, Hundal HS: Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells. Biochem J 2006, 399:473–481.

    Article  PubMed  CAS  Google Scholar 

  5. Lee JS, Pinnamaneni SK, Eo SJ, et al.: Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol 2006, 100:1467–1474.

    Article  PubMed  CAS  Google Scholar 

  6. Matsuzaka T, Shimano H, Yahagi N, et al.: Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat Med 2007, 13:1193–1202.

    Article  PubMed  CAS  Google Scholar 

  7. Cohen P, Friedman JM: Leptin and the control of metabolism: role for stearoyl-CoA desaturase-1 (SCD-1). J Nutr 2004, 134:2455s–2463s.

    PubMed  CAS  Google Scholar 

  8. Hulver MW, Berggren JR, Carper MJ, et al.: Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab 2005, 2:251–261.

    Article  PubMed  CAS  Google Scholar 

  9. Kakuma T, Lee Y, Unger RH: Effects of leptin, troglitazone, and dietary fat on stearoyl CoA desaturase. Biochem Biophys Res Commun 2002, 297:1259–1263.

    Article  PubMed  CAS  Google Scholar 

  10. Anderson EJ, Yamazaki H, Neufer PD: Induction of endogenous uncoupling protein 3 suppresses mitochondrial oxidant emission during fatty acid-supported respiration. J Biol Chem 2007, 282:31257–31266.

    Article  PubMed  CAS  Google Scholar 

  11. Thrush AB, Heigenhauser GJ, Mullen KL, et al.: Palmitate acutely induces insulin resistance in isolated muscle from obese but not lean humans. Am J Physiol Regul Integr Comp Physiol 2008, 294:R1205–R1212.

    PubMed  CAS  Google Scholar 

  12. Shulman GI: Cellular mechanisms of insulin resistance. J Clin Invest 2000, 106:171–176.

    Article  PubMed  CAS  Google Scholar 

  13. Salmeron J, Hu FB, Manson JE, et al.: Dietary fat intake and risk of type 2 diabetes in women. Am J Clin Nutr 2001, 73:1019–1026.

    PubMed  CAS  Google Scholar 

  14. Baur LA, O’Connor J, Pan DA, et al.: 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.

    Article  PubMed  CAS  Google Scholar 

  15. Bollag GE, Roth RA, Beaudoin J, et al.: Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity. Proc Natl Acad Sci U S A 1986, 83:5822–5824.

    Article  PubMed  CAS  Google Scholar 

  16. Itani SI, Ruderman NB, Schmieder F, Boden G: Lipidinduced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 2002, 51:2005–2011.

    Article  PubMed  CAS  Google Scholar 

  17. Chavez JA, Summers SA: Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. Arch Biochem Biophys 2003, 419:101–109.

    Article  PubMed  CAS  Google Scholar 

  18. Summers SA: Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 2006, 45:42–72.

    Article  PubMed  CAS  Google Scholar 

  19. Powell DJ, Turban S, Gray A, et al.: Intracellular ceramide synthesis and protein kinase Czeta activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells. Biochem J 2004, 382:619–629.

    Article  PubMed  CAS  Google Scholar 

  20. Turpin SM, Lancaster GI, Darby I, et al.: Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance. Am J Physiol Endocrinol Metab 2006, 291:E1341–E1350.

    Article  PubMed  CAS  Google Scholar 

  21. Hardy S, El Assaad W, Przybytkowski E, et al.: Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin. J Biol Chem 2003, 278:31861–31870.

    Article  PubMed  CAS  Google Scholar 

  22. Koves TR, Li P, An J, et al.: PPARgamma coactivator-1alpha -mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem 2005, 280:33588–33598.

    Article  PubMed  CAS  Google Scholar 

  23. Coll T, Jove M, Rodriguez-Calvo R, et al.: Palmitate-mediated downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1alpha in skeletal muscle cells involves MEK1/2 and nuclear factor-kappaB activation. Diabetes 2006, 55:2779–2787.

    Article  PubMed  CAS  Google Scholar 

  24. Shi H, Kokoeva MV, Inouye K, et al.: TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 2006, 116:3015–3025.

    Article  PubMed  CAS  Google Scholar 

  25. Lee JY, Sohn KH, Rhee SH, Hwang D: Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 2001, 276:16683–16689.

    Article  PubMed  CAS  Google Scholar 

  26. Ghosh S, May MJ, Kopp EB: NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 1998, 16:225–260.

    Article  PubMed  CAS  Google Scholar 

  27. Ajuwon KM, Spurlock ME: Palmitate activates the NF-kappaB transcription factor and induces IL-6 and TNFalpha expression in 3T3-L1 adipocytes. J Nutr 2005, 135:1841–1846.

    PubMed  CAS  Google Scholar 

  28. Jove M, Planavila A, Sanchez RM, et al.: Palmitate induces tumor necrosis factor-alpha expression in C2C12 skeletal muscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation. Endocrinology 2006, 147:552–561.

    Article  PubMed  CAS  Google Scholar 

  29. Jove M, Planavila A, Laguna JC, Vazquez-Carrera M: Palmitate-induced interleukin 6 production is mediated by protein kinase C and nuclear-factor kappaB activation and leads to glucose transporter 4 down-regulation in skeletal muscle cells. Endocrinology 2005, 146:3087–3095.

    Article  PubMed  CAS  Google Scholar 

  30. Sinha S, Perdomo G, Brown NF, O’Doherty RM: Fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition of activation and nuclear localization of nuclear factor kappa B. J Biol Chem 2004, 279:41294–41301.

    Article  PubMed  CAS  Google Scholar 

  31. Jove M, Laguna JC, Vazquez-Carrera M: Agonist-induced activation releases peroxisome proliferator-activated receptor beta/delta from its inhibition by palmitate-induced nuclear factor-kappaB in skeletal muscle cells. Biochim Biophys Acta 2005, 1734:52–61.

    PubMed  CAS  Google Scholar 

  32. Shoelson SE, Lee J, Goldfine AB: Inflammation and insulin resistance. J Clin Invest 2006, 116:1793–1801.

    Article  PubMed  CAS  Google Scholar 

  33. Odegaard JI, Ricardo-Gonzalez RR, Red EA, et al.: Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 2008, 7:496–507.

    Article  PubMed  CAS  Google Scholar 

  34. Kien CL, Bunn JY, Ugrasbul F: Increasing dietary palmitic acid decreases fat oxidation and daily energy expenditure. Am J Clin Nutr 2005, 82:320–326.

    PubMed  CAS  Google Scholar 

  35. Jones PJH, Schoeller DA: Polyunsaturated:saturated ratio of diet fat influences energy substrate utilization in the human. Metabolism 1988, 37:145–151.

    Article  PubMed  CAS  Google Scholar 

  36. Kien CL, Bunn JY: Gender alters the effects of palmitate and oleate on fat oxidation and energy expenditure. Obesity 2008, 16:29–33.

    Article  PubMed  CAS  Google Scholar 

  37. Koves TR, Ussher JR, Noland RC, et al.: Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 2008, 7:45–56.

    Article  PubMed  CAS  Google Scholar 

  38. Turner N, Bruce CR, Beale SM, et al.: Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents. Diabetes 2007, 56:2085–2092.

    Article  PubMed  CAS  Google Scholar 

  39. Houstis N, Rosen ED, Lander ES: Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006, 440:944–948.

    Article  PubMed  CAS  Google Scholar 

  40. Hancock CR, Han DH, Chen M, et al.: High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci U S A 2008, 105:7815–7820.

    Article  PubMed  CAS  Google Scholar 

  41. Feskens EJ, Virtanen SM, Rasanen L et al.: Dietary factors determining diabetes and impaired glucose tolerance. A 20-year follow-up of the Finnish and Dutch cohorts of the Seven Countries Study. Diabetes Care 1995, 18:1104–1112.

    Article  PubMed  CAS  Google Scholar 

  42. Hu FB, van Dam RM, Liu S: Diet and risk of type 2 diabetes: the role of types of fat and carbohydrate. Diabetologia 2001, 44:805–817.

    Article  PubMed  CAS  Google Scholar 

  43. Vessby B: Dietary fat and insulin action in humans. Br J Nutr 2000, 83(Suppl 1):S91–S96.

    PubMed  CAS  Google Scholar 

  44. Riserus U: Fatty acids and insulin sensitivity. Curr Opin Clin Nutr Metab Care 2008, 11:100–105.

    Article  PubMed  CAS  Google Scholar 

  45. Vessby B, Unsitupa M, Hermansen K, et al.: Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: the KANWU study. Diabetologia 2001, 44:312–319.

    Article  PubMed  CAS  Google Scholar 

  46. Perez-Jimenez F, Lopez-Miranda J, Pinillos MD, et al.: A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons. Diabetologia 2001, 44:2038–2043.

    Article  PubMed  CAS  Google Scholar 

  47. Garg A: High-monounsaturated-fat diets for patients with diabetes mellitus: a meta-analysis. Am J Clin Nutr 1998, 67(3 Suppl):577S–582S.

    PubMed  CAS  Google Scholar 

  48. Christiansen E, Schnider S, Palmvig B, et al.: Intake of a diet high in trans monounsaturated fatty acids or saturated fatty acids. Effects on postprandial insulinemia and glycemia in obese patients with NIDDM. Diabetes Care 1997, 20:881–887.

    Article  PubMed  CAS  Google Scholar 

  49. Musso G, Gambino R, De Michieli F, et al.: Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003, 37:909–916.

    Article  PubMed  CAS  Google Scholar 

  50. Clore JN, Stillman JS, Li J, et al.: Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose metabolism in humans. Am J Physiol Endocrinol Metab 2004, 287:E358–E365.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Craig Lawrence Kien.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kien, C.L. Dietary interventions for metabolic syndrome: Role of modifying dietary fats. Curr Diab Rep 9, 43–50 (2009). https://doi.org/10.1007/s11892-009-0009-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-009-0009-6

Keywords

Navigation