Journal of Bioenergetics and Biomembranes

, Volume 46, Issue 1, pp 33–44 | Cite as

Dietary fat, fatty acid saturation and mitochondrial bioenergetics

  • Liping Yu
  • Brian D. Fink
  • Judith A. Herlein
  • Christine L. Oltman
  • Kathryn G. Lamping
  • William I. Sivitz
Article

Abstract

Fat intake alters mitochondrial lipid composition which can affect function. We used novel methodology to assess bioenergetics, including simultaneous ATP and reactive oxygen species (ROS) production, in liver and heart mitochondria of C57BL/6 mice fed diets of variant fatty acid content and saturation. Our methodology allowed us to clamp ADP concentration and membrane potential (ΔΨ) at fixed levels. Mice received a control diet for 17–19 weeks, a high-fat (HF) diet (60 % lard) for 17–19 weeks, or HF for 12 weeks followed by 6–7 weeks of HF with 50 % of fat as menhaden oil (MO) which is rich in n-3 fatty acids. ATP production was determined as conversion of 2-deoxyglucose to 2-deoxyglucose phosphate by NMR spectroscopy. Respiration and ATP production were significantly reduced at all levels of ADP and resultant clamped ΔΨ in liver mitochondria from mice fed HF compared to controls. At given ΔΨ, ROS production per mg mitochondrial protein, per unit respiration, or per ATP generated were greater for liver mitochondria of HF-fed mice compared to control or MO-fed mice. Moreover, these ROS metrics began to increase at a lower ΔΨ threshold. Similar, but less marked, changes were observed in heart mitochondria of HF-fed mice compared to controls. No changes in mitochondrial bioenergetics were observed in studies of separate mice fed HF versus control for only 12 weeks. In summary, HF feeding of sufficient duration impairs mitochondrial bioenergetics and is associated with a greater ROS “cost” of ATP production compared to controls. These effects are, in part, mitigated by MO.

Keywords

Mitochondria ATP Reactive oxygen Fatty acids Respiration 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

10863_2013_9530_MOESM1_ESM.docx (170 kb)
ESM 1(DOCX 170 kb)

References

  1. Al-Gubory KH (2012) Mitochondria: omega-3 in the route of mitochondrial reactive oxygen species. Int J Biochem Cell Biol 44:1569–1573CrossRefGoogle Scholar
  2. Aoun M, Feillet-Coudray C, Fouret G, Chabi B, Crouzier D, Ferreri C, Chatgilialoglu C, Wrutniak-Cabello C, Cristol JP, Carbonneau MA, Coudray C (2012a) Rat liver mitochondrial membrane characteristics and mitochondrial functions are more profoundly altered by dietary lipid quantity than by dietary lipid quality: effect of different nutritional lipid patterns. Br J Nutr 107:647–659CrossRefGoogle Scholar
  3. Aoun M, Fouret G, Michel F, Bonafos B, Ramos J, Cristol JP, Carbonneau MA, Coudray C, Feillet-Coudray C (2012b) Dietary fatty acids modulate liver mitochondrial cardiolipin content and its fatty acid composition in rats with non alcoholic fatty liver disease. J Bioenerg Biomembr 44:439–452CrossRefGoogle Scholar
  4. Armstrong MB, Towle HC (2001) Polyunsaturated fatty acids stimulate hepatic UCP-2 expression via a PPARalpha-mediated pathway. Am J Physiol Endocrinol Metab 281:E1197–E1204Google Scholar
  5. Bax A, Davis DG (1985) MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy. J Magn Reson 65:355–360Google Scholar
  6. Boudina S, Sena S, Theobald H, Sheng X, Wright JJ, Hu XX, Aziz S, Johnson JI, Bugger H, Zaha VG, Abel ED (2007) Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 56:2457–2466CrossRefGoogle Scholar
  7. Brand MD (2010) The sites and topology of mitochondrial superoxide production. Exp Gerontol 45:466–472CrossRefGoogle Scholar
  8. Brand MD, Esteves TC (2005) Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab 2:85–93CrossRefGoogle Scholar
  9. Braunschweiler L, Ernst RR (1983) Coherence transfer by isotropic mixing: application to proton correlation spectroscopy. J Magn Reson 53:521–528Google Scholar
  10. Cadenas S, Buckingham JA, Samec S, Seydoux J, Din N, Dulloo AG, Brand MD (1999) UCP2 and UCP3 rise in starved rat skeletal muscle but mitochondrial proton conductance is unchanged. FEBS Lett 462:257–260CrossRefGoogle Scholar
  11. Chen Y, Hagopian K, Bibus D, Villalba JM, Lopez-Lluch G, Navas P, Kim K, McDonald RB, Ramsey JJ (2013) The influence of dietary lipid composition on liver mitochondria from mice following 1 month of calorie restriction. Biosci Rep 33:83–95Google Scholar
  12. da-Silva WS, Gomez-Puyou A, de Gomez-Puyou MT, Moreno-Sanchez R, De Felice FG, de Meis L, Oliveira MF, Galina A (2004) Mitochondrial bound hexokinase activity as a preventive antioxidant defense: steady-state ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria. J Biol Chem 279:39846–39855CrossRefGoogle Scholar
  13. Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A (1995) NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6:277–293CrossRefGoogle Scholar
  14. Fink BD, Herlein JA, Almind K, Cinti S, Kahn CR, Sivitz WI (2007) The mitochondrial proton leak in obesity-resistant and obesity-prone mice. Am J Physiol Regul Integr Comp Physiol 293:R1773–R1780CrossRefGoogle Scholar
  15. Flachs P, Horakova O, Brauner P, Rossmeisl M, Pecina P, Franssen-van Hal N, Ruzickova J, Sponarova J, Drahota Z, Vlcek C, Keijer J, Houstek J, Kopecky J (2005) Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 48:2365–2375CrossRefGoogle Scholar
  16. Fukui M, Kang KS, Okada K, Zhu BT (2013) EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. J Cell Biochem 114:192–203CrossRefGoogle Scholar
  17. Glancy B, Willis WT, Chess DJ, Balaban RS (2013) Effect of calcium on the oxidative phosphorylation cascade in skeletal muscle mitochondria. Biochemistry 52:2793–2809CrossRefGoogle Scholar
  18. Hagopian K, Weber KL, Hwee DT, Van Eenennaam AL, Lopez-Lluch G, Villalba JM, Buron I, Navas P, German JB, Watkins SM, Chen Y, Wei A, McDonald RB, Ramsey JJ (2010) Complex I-associated hydrogen peroxide production is decreased and electron transport chain enzyme activities are altered in n-3 enriched fat-1 mice. PLoS One 5:e12696CrossRefGoogle Scholar
  19. Hasselbaink DM, Roemen TH, van der Vusse GJ (2002) Protein acylation in the cardiac muscle like cell line, H9c2. Mol Cell Biochem 239:101–112CrossRefGoogle Scholar
  20. Herlein JA, Fink BD, O'Malley Y, Sivitz WI (2009) Superoxide and respiratory coupling in mitochondria of insulin-deficient diabetic rats. Endocrinology 150:46–55CrossRefGoogle Scholar
  21. Herlein JA, Fink BD, Henry DM, Yorek MA, Teesch LM, Sivitz WI (2011) Mitochondrial superoxide and coenzyme Q in insulin-deficient rats: increased electron leak. Am J Physiol Regul Integr Comp Physiol 301:R1616–R1624CrossRefGoogle Scholar
  22. Hoch FL (1992) Cardiolipins and biomembrane function. Biochim Biophys Acta 1113:71–133CrossRefGoogle Scholar
  23. Johnson BA, Blevins RA (1994) NMR view: a computer program for the visualization and analysis of NMR data. J Biomol NMR 4:603–614CrossRefGoogle Scholar
  24. Johnson JA, Ogbi M (2011) Targeting the F1Fo ATP Synthase: modulation of the body’s powerhouse and its implications for human disease. Curr Med Chem 18:4684–4714CrossRefGoogle Scholar
  25. Kang KS, Wang P, Yamabe N, Fukui M, Jay T, Zhu BT (2010) Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation. PLoS One 5:e10296CrossRefGoogle Scholar
  26. Lambert AJ, Brand MD (2004) Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I). J Biol Chem 279:39414–39420CrossRefGoogle Scholar
  27. Lamping KG, Nuno DW, Coppey LJ, Holmes AJ, Hu S, Oltman CL, Norris AW, Yorek MA (2013) Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction. Diabetes Obes Metab 15:144–152CrossRefGoogle Scholar
  28. McMillin JB, Bick RJ, Benedict CR (1992) Influence of dietary fish oil on mitochondrial function and response to ischemia. Am J Physiol 263:H1479–H1485Google Scholar
  29. Nyberg NT, Sørensen OW (2006) Multiplicity-edited broadband HMBC NMR spectra. Magn Reson Chem 44:451–454CrossRefGoogle Scholar
  30. Oliveira CP, Coelho AM, Barbeiro HV, Lima VM, Soriano F, Ribeiro C, Molan NA, Alves VA, Souza HP, Machado MC, Carrilho FJ (2006) Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease. Braz J Med Biol Res 39:189–194Google Scholar
  31. O'Malley Y, Fink BD, Ross NC, Prisinzano TE, Sivitz WI (2006) Reactive oxygen and targeted antioxidant administration in endothelial cell mitochondria. J Biol Chem 281:39766–39775CrossRefGoogle Scholar
  32. Patergnani S, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, Giorgi C, Marchi S, Missiroli S, Poletti F, Rimessi A, Duszynski J, Wieckowski MR, Pinton P (2011) Calcium signaling around Mitochondria Associated Membranes (MAMs). Cell Commun Signal 9:19CrossRefGoogle Scholar
  33. Pepe S, Tsuchiya N, Lakatta EG, Hansford RG (1999) PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH. Am J Physiol 276:H149–H158Google Scholar
  34. Pillon NJ, Croze ML, Vella RE, Soulere L, Lagarde M, Soulage CO (2012) The lipid peroxidation by-product 4-hydroxy-2-nonenal (4-HNE) induces insulin resistance in skeletal muscle through both carbonyl and oxidative stress. Endocrinology 153:2099–2111CrossRefGoogle Scholar
  35. Pires KM, Ilkun O, Valente M, Boudina S (2013) Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice. Obesity (Silver Spring)Google Scholar
  36. Rance M, Sørensen OW, Bodenhausen G, Wagner G, Ernst RR, Wüthrich K (1983) Improved spectral resolution in COSY 1H NMR spectra of proteins via double quantum filtering. Biochem Biophys Res Commun 117:479–485CrossRefGoogle Scholar
  37. Rhee SG, Chang TS, Jeong W, Kang D (2010) Methods for detection and measurement of hydrogen peroxide inside and outside of cells. Mol Cell 29:539–549CrossRefGoogle Scholar
  38. Rohrbach S (2009) Effects of dietary polyunsaturated fatty acids on mitochondria. Curr Pharm Des 15:4103–4116CrossRefGoogle Scholar
  39. Stillwell W, Jenski LJ, Crump FT, Ehringer W (1997) Effect of docosahexaenoic acid on mouse mitochondrial membrane properties. Lipids 32:497–506CrossRefGoogle Scholar
  40. Strauss M, Hofhaus G, Schroder RR, Kuhlbrandt W (2008) Dimer ribbons of ATP synthase shape the inner mitochondrial membrane. EMBO J 27:1154–1160CrossRefGoogle Scholar
  41. Szendroedi J, Phielix E, Roden M (2012) The role of mitochondria in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol 8:92–103CrossRefGoogle Scholar
  42. Tsalouhidou S, Argyrou C, Theofilidis G, Karaoglanidis D, Orfanidou E, Nikolaidis MG, Petridou A, Mougios V (2006) Mitochondrial phospholipids of rat skeletal muscle are less polyunsaturated than whole tissue phospholipids: implications for protection against oxidative stress. J Anim Sci 84:2818–2825CrossRefGoogle Scholar
  43. Wang HT, Liu CF, Tsai TH, Chen YL, Chang HW, Tsai CY, Leu S, Zhen YY, Chai HT, Chung SY, Chua S, Yen CH, Yip HK (2012) Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice. J Transl Med 10:145CrossRefGoogle Scholar
  44. Wojtczak L, Zaluska H, Wroniszewska A, Wojtczak AB (1972) Assay for the intactness of the outer membrane in isolated mitochondria. Acta Biochim Pol 19:227–234Google Scholar
  45. Yamagishi SI, Edelstein D, Du XL, Kaneda Y, Guzman M, Brownlee M (2001) Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem 276:25096–25100CrossRefGoogle Scholar
  46. Yu L, Fink BD, Herlein JA, Sivitz WI (2013) Mitochondrial function in diabetes: novel methodology and new insight. Diabetes 62:1833–1842CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2013

Authors and Affiliations

  • Liping Yu
    • 1
  • Brian D. Fink
    • 2
  • Judith A. Herlein
    • 2
  • Christine L. Oltman
    • 3
  • Kathryn G. Lamping
    • 4
  • William I. Sivitz
    • 2
    • 5
  1. 1.NMR Core Facility and Department of BiochemistryUniversity of IowaIowa CityUSA
  2. 2.Department of Internal Medicine/EndocrinologyUniversity of Iowa and the Iowa City Veterans Affairs Medical CenterIowa CityUSA
  3. 3.Department of Internal Medicine/CardiologyUniversity of Iowa and the Iowa City Veterans Affairs Medical CenterIowa CityUSA
  4. 4.Department of PharmacologyUniversity of Iowa and the Iowa City Veterans Affairs Medical CenterIowa CityUSA
  5. 5.Department of Internal Medicine, Division of Endocrinology and MetabolismThe University of Iowa Hospitals and ClinicsIowa CityUSA

Personalised recommendations