Nutr Res Pract.  2013 Dec;7(6):481-487.

Effects of d-alpha-tocopherol supplements on lipid metabolism in a high-fat diet-fed animal model

Affiliations
  • 1Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, 1732 Deogyeong-daero, Giheung-gu, Yongin, Gyeonggi 446-701, Korea. rwcho@khu.ac.kr
  • 2Research Institute of Medical Nutrition, Kyung Hee University, Seoul 130-701, Korea.

Abstract

High-fat diet up-regulates either insulin resistance or triglycerides, which is assumed to be related to the expression of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma. The beneficial effects of vitamin E on insulin resistance are well known; however, it is not clear if vitamin E with a high-fat diet alters the expression of PPAR-alpha and PPAR-gamma. We investigated the effects of d-alpha-tocopherol supplementation on insulin sensitivity, blood lipid profiles, lipid peroxidation, and the expression of PPAR-alpha and PPAR-gamma in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat, or a HF diet plus d-alpha-tocopherol (HF-E) for a period of 20 weeks. The results showed that the HF diet induced insulin resistance and altered the lipid profile, specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05). In this animal model, supplementation with d-alpha-tocopherol improved insulin resistance as well as the serum levels of TG and very-low-density lipoprotein-cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-alpha expression and decreasing PPAR-gamma expression. In conclusion, the oral administration of d-alpha-tocopherol with a high-fat diet had positive effects on insulin resistance, lipid profiles, and oxidative stress through the expression of PPAR-alpha and PPAR-gamma in a high-fat diet-fed male mice.

Keyword

High fat diet; supplementation; d-alpha-tocopherol; insulin resistance

MeSH Terms

Administration, Oral
Animals*
Cholesterol
Diet
Diet, High-Fat
Humans
Insulin Resistance
Lipid Metabolism*
Lipid Peroxidation
Liver
Male
Malondialdehyde
Mice
Models, Animal*
Oxidative Stress
Peroxisomes
Triglycerides
Vitamin E
Vitamins
Cholesterol
Malondialdehyde
Triglycerides
Vitamin E
Vitamins

Figure

  • Fig. 1 Levels of malondealdehyde in (A) serum and (B) liver. Data are means ± S.E. a-cValues with different superscript letters are significantly different at P < 0.05 by Duncan's multiple range test based on analysis of variance. CON; mice fed regular diet (10% of calories derived from fat) with distilled water as a vehicle (0.1 ml, p.o.) for 20 weeks. HF; mice fed high-fat diet (45% of calories derived from fat) with distilled water as a vehicle (0.1 ml, p.o.) for 20 weeks. HF-E; mice fed high-fat diet (45% of calories derived from fat) with d-α-tocopherol as a vehicle for 20 weeks. D-α-tocopherol (100 IU/kgBW, p.o.); freshly prepared by dissolving in distilled water after triturating with Tween 20, MDA; malondialdehyde

  • Fig. 2 Expression of (A) PPAR-α and (B) PPAR-γ in the liver. CON; mice fed regular diet (10% of calories derived from fat) with distilled water as a vehicle (0.1 ml, p.o.) for 20 weeks. HF; mice fed high-fat diet (45% of calories derived from fat) with distilled water as a vehicle (0.1 ml, p.o.) for 20 weeks. HF-E; mice fed high-fat diet (45% of calories derived from fat) with d-α-tocopherol as a vehicle for 20 weeks. D-α-tocopherol (100 IU/kgBW, p.o.); freshly prepared by dissolving in distilled water after triturating with Tween 20. PPAR-α; peroxisome proliferator-activated receptor-alpha. PPAR-γ; peroxisome proliferator-activated receptorgamma


Reference

1. Lovejoy JC, Champagne CM, Smith SR, DeLany JP, Bray GA, Lefevre M, Denkins YM, Rood JC. Relationship of dietary fat and serum cholesterol ester and phospholipid fatty acids to markers of insulin resistance in men and women with a range of glucose tolerance. Metabolism. 2001; 50:86–92.
Article
2. Mayer-Davis EJ, Monaco JH, Hoen HM, Carmichael S, Vitolins MZ, Rewers MJ, Haffner SM, Ayad MF, Bergman RN, Karter AJ. Dietary fat and insulin sensitivity in a triethnic population: the role of obesity. The Insulin Resistance Atherosclerosis Study (IRAS). Am J Clin Nutr. 1997; 65:79–87.
Article
3. Lovejoy JC, Windhauser MM, Rood JC, de la Bretonne JA. Effect of a controlled high-fat versus low-fat diet on insulin sensitivity and leptin levels in African-American and Caucasian women. Metabolism. 1998; 47:1520–1524.
Article
4. Hardwick JP, Osei-Hyiaman D, Wiland H, Abdelmegeed MA, Song BJ. PPAR/RXR regulation of fatty acid metabolism and fatty acid omega-hydroxylase (CYP4) isozymes: implications for prevention of lipotoxicity in fatty liver disease. PPAR Res. 2009; 2009:952734.
5. Carmena R. Type 2 diabetes, dyslipidemia, and vascular risk: rationale and evidence for correcting the lipid imbalance. Am Heart J. 2005; 150:859–870.
Article
6. Sugden MC, Holness MJ. Potential role of peroxisome proliferator-activated receptor-alpha in the modulation of glucose-stimulated insulin secretion. Diabetes. 2004; 53:Suppl 1. S71–S81.
7. Robinson E, Grieve DJ. Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease. Pharmacol Ther. 2009; 122:246–263.
Article
8. Manning PJ, Sutherland WH, Walker RJ, Williams SM, De Jong SA, Ryalls AR, Berry EA. Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects. Diabetes Care. 2004; 27:2166–2171.
Article
9. Raso GM, Esposito E, Iacono A, Pacilio M, Cuzzocrea S, Canani RB, Calignano A, Meli R. Comparative therapeutic effects of metformin and vitamin E in a model of non-alcoholic steatohepatitis in the young rat. Eur J Pharmacol. 2009; 604:125–131.
Article
10. González R, Collado JA, Nell S, Briceño J, Tamayo MJ, Fraga E, Bernardos A, López-Cillero P, Pascussi JM, Rufián S, Vilarem MJ, De la Mata M, Brigelius-Flohe R, Maurel P, Muntané J. Cytoprotective properties of alpha-tocopherol are related to gene regulation in cultured D-galactosamine-treated human hepatocytes. Free Radic Biol Med. 2007; 43:1439–1452.
11. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226:497–509.
Article
12. Winzell MS, Ahrén B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes. 2004; 53:Suppl 3. S215–S219.
13. Facchini FS, Humphreys MH, DoNascimento CA, Abbasi F, Reaven GM. Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols. Am J Clin Nutr. 2000; 72:776–779.
Article
14. Muis MJ, Stolk RP, Princen HM, Van Dam PS, Dikkeschei LD, Grobbee DE, Bilo HJ. alpha-Tocopherol levels in plasma in new-onset, insulin-dependent diabetes mellitus. Eur J Intern Med. 2004; 15:371–374.
Article
15. Paolisso G, DAmore A, Giugliano D, Ceriello A, Varricchio M, D'Onofrio F. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr. 1993; 57:650–656.
Article
16. Costacou T, Ma B, King IB, Mayer-Davis EJ. Plasma and dietary vitamin E in relation to insulin secretion and sensitivity. Diabetes Obes Metab. 2008; 10:223–228.
Article
17. Codoñer-Franch P, Navarro-Ruiz A, Fernández-Ferri M, Arilla-Codoñer A, Ballester-Asensio E, Valls-Bellés V. A matter of fat: insulin resistance and oxidative stress. Pediatr Diabetes. 2012; 13:392–399.
Article
18. Rudich A, Tirosh A, Potashnik R, Khamaisi M, Bashan N. Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes. Diabetologia. 1999; 42:949–957.
Article
19. Maddux BA, See W, Lawrence JC Jr, Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of α-lipoic acid. Diabetes. 2001; 50:404–410.
Article
20. Vinayagamoorthi R, Bobby Z, Sridhar MG. Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance. J Endocrinol. 2008; 197:287–296.
Article
21. Altavilla D, Deodato B, Campo GM, Arlotta M, Miano M, Squadrito G, Saitta A, Cucinotta D, Ceccarelli S, Ferlito M, Tringali M, Minutoli L, Caputi AP, Squadrito F. IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-kappaB and reduces the inflammatory response in myocardial ischemia-reperfusion injury. Cardiovasc Res. 2000; 47:515–528.
Article
22. Terra X, Montagut G, Bustos M, Llopiz N, Ardèvol A, Bladé C, Fernández-Larrea J, Pujadas G, Salvadó J, Arola L, Blay M. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem. 2009; 20:210–218.
Article
23. Azzi A, Gysin R, Kempná P, Munteanu A, Villacorta L, Visarius T, Zingg JM. Regulation of gene expression by alpha-tocopherol. Biol Chem. 2004; 385:585–591.
24. Braissant O, Foufelle F, Scotto C, Dauça M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology. 1996; 137:354–366.
Article
25. Yu S, Matsusue K, Kashireddy P, Cao WQ, Yeldandi V, Yeldandi AV, Rao MS, Gonzalez FJ, Reddy JK. Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (PPARgamma1) overexpression. J Biol Chem. 2003; 278:498–505.
Article
26. Yakaryilmaz F, Guliter S, Savas B, Erdem O, Ersoy R, Erden E, Akyol G, Bozkaya H, Ozenirler S. Effects of vitamin E treatment on peroxisome proliferator-activated receptor-alpha expression and insulin resistance in patients with non-alcoholic steatohepatitis: results of a pilot study. Intern Med J. 2007; 37:229–235.
Article
27. Serisier S, Leray V, Poudroux W, Magot T, Ouguerram K, Nguyen P. Effects of green tea on insulin sensitivity, lipid profile and expression of PPARalpha and PPARgamma and their target genes in obese dogs. Br J Nutr. 2008; 99:1208–1216.
Article
28. Tsuboyama-Kasaoka N, Takahashi M, Kim H, Ezaki O. Up-regulation of liver uncoupling protein-2 mRNA by either fish oil feeding or fibrate administration in mice. Biochem Biophys Res Commun. 1999; 257:879–885.
Article
29. Srivastava RA. Fenofibrate ameliorates diabetic and dyslipidemic profiles in KKAy mice partly via down-regulation of 11beta-HSD1, PEPCK and DGAT2. Comparison of PPARalpha, PPAR gamma, and liver × receptor agonists. Eur J Pharmacol. 2009; 607:258–263.
Article
30. Matsusue K, Haluzik M, Lambert G, Yim SH, Gavrilova O, Ward JM, Brewer B Jr, Reitman ML, Gonzalez FJ. Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J Clin Invest. 2003; 111:737–747.
Article
Full Text Links
  • NRP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr