Journal of Bioenergetics and Biomembranes

, Volume 43, Issue 1, pp 19–23 | Cite as

Mitochondrial energy metabolism and redox responses to hypertriglyceridemia

  • Luciane C. Alberici
  • Anibal E. Vercesi
  • Helena C. F. Oliveira


In this work we review recent findings that explain how mitochondrial bioenergetic functions and redox state respond to a hyperlipidemic in vivo environment and may contribute to the maintenance of a normal metabolic phenotype. The experimental model utilized to evidence these adaptive mechanisms is especially useful for these studies since it exhibits genetic hypertriglyceridemia and avoids complications introduced by high fat diets. Liver from hypertrigliceridemic (HTG) mice have a greater content of glycerolipids together with increased mitochondrial free fatty acid oxidation. HTG liver mitochondria have a higher resting respiration rate but normal oxidative phosphorylation efficiency. This is achieved by higher activity of the mitochondrial potassium channel sensitive to ATP (mitoKATP). The mild uncoupling mediated by mitoKATP accelerates respiration rates and reduces reactive oxygen species generation. Although this response is not sufficient to inhibit lipid induced extra-mitochondrial oxidative stress in whole liver cells it avoids amplification of this redox imbalance. Furthermore, higher mitoKATP activity increases liver, brain and whole body metabolic rates. These mitochondrial adaptations may explain why these HTG mice do not develop insulin resistance and obesity even under a severe hyperlipidemic state. On the contrary, when long term high fat diets are employed, insulin resistance, fatty liver and obesity develop and mitochondrial adaptations are inefficient to counteract energy and redox imbalances.


Hypertriglyceridemia Mitochondrial uncoupling Redox state Mitochondrial ATP-sensitive potassium channels  


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aalto-Setala K, Fisher EA, Chen X, Chajek-Shaul T, Hayek T, Zechner R, Walsh A, Ramakrishnan R, Ginsberg HN, Breslow JL (1992) J Clin Invest 90:1889–1900CrossRefGoogle Scholar
  2. Alberici LC, Oliveira HC, Bighetti EJ, de Faria EC, Degaspari GR, Souza CT, Vercesi AE (2003) J Bioenerg Biomembr 35:451–457CrossRefGoogle Scholar
  3. Alberici LC, Oliveira HC, Patrício PR, Kowaltowski AJ, Vercesi AE (2006) Gastroenterology 131:1228–1234CrossRefGoogle Scholar
  4. Alberici LC, Oliveira HC, Paim BA, Mantello CC, Augusto AC, Zecchin KG, Gurgueira SA, Kowaltowski AJ, Vercesi AE (2009) Free Radic Biol Med 47:1432–1439CrossRefGoogle Scholar
  5. Amaral ME, Oliveira HC, Carneiro EM, Delghingaro-Augusto V, Vieira EC, Berti JA, Boschero AC (2002) Horm Metab Res 34:21–26CrossRefGoogle Scholar
  6. Boveris A (1977) Adv Exp Med Biol 78:67–82Google Scholar
  7. Cardoso AR, Cabral-Costa JV, Kowaltowski AJ (2010) J Bioenerg Biomembr 42:245–253CrossRefGoogle Scholar
  8. Cighetti G, Bortone L, Sala S, Allevi P (2001) Arch Biochem Biophys 389:195–200CrossRefGoogle Scholar
  9. Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB, Piercy V, Carter SA, Lehner I, Smith SA, Beeley LJ, Godden RJ, Herrity N, Skehel M, Changani KK, Hockings PD, Reid DG, Squires SM, Hatcher J, Trail B, Latcham J, Rastan S, Harper AJ, Cadenas S, Buckingham JA, Brand MD, Abuin A (2000) Nature 406:415–418CrossRefGoogle Scholar
  10. Després JP, Lemieux I (2006) Nature 444:881–887CrossRefGoogle Scholar
  11. Facundo HT, de Paula JG, Kowaltowski AJ (2007) Free Radic Biol Med 42:1039–1048CrossRefGoogle Scholar
  12. Fornazari M, de Paula JG, Castilho RF, Kowaltowski AJ (2008) J Neurosci Res 86:1548–1556CrossRefGoogle Scholar
  13. Garlid KD, Paucek P (2003) Biochim Biophys Acta 1606:23–41CrossRefGoogle Scholar
  14. Garlid KD, Jaburek M, Jezek P, Varecha M (2000) Biochim Biophys Acta 1459:383–389CrossRefGoogle Scholar
  15. Greenberg JA (1999) Med Hypotheses 52:15–22CrossRefGoogle Scholar
  16. Greenberg JA, Boozer CN (2000) Mech Ageing Dev 113:37–48CrossRefGoogle Scholar
  17. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, American Heart Association, National Heart, Lung, and Blood Institute (2004) Circulation 109:433–438CrossRefGoogle Scholar
  18. Hesselink MK, Mensink M, Schrauwen P (2003) Obes Res 11:1429–1443CrossRefGoogle Scholar
  19. Ito Y, Azrolan N, O’Connell A, Walsh A, Breslow JL (1990) Science 249:790–793CrossRefGoogle Scholar
  20. Jezek P, Garlid KD (1998) Int J Biochem Cell Biol 30:1163–1168CrossRefGoogle Scholar
  21. Kontani Y, Wang Y, Kimura K, Inokuma KI, Saito M, Suzuki-Miura T, Wang Z, Sato Y, Mori N, Yamashita H (2005) Aging Cell 4:147–155CrossRefGoogle Scholar
  22. Kopecky J, Clarke G, Enerback S, Spiegelman B, Kozak LP (1995) J Clin Invest 96:2914–2923CrossRefGoogle Scholar
  23. Krylova IB, Kachaeva EV, Rodionova OM, Negoda AE, Evdokimova NR, Balina MI, Sapronov NS, Mironova GD (2006) Exp Gerontol 41:697–703CrossRefGoogle Scholar
  24. Leclercq IA, Farrell GC, Field J, Bell DR, Gonzalez FJ, Robertson GR (2000) J Clin Invest 105:1067–1075CrossRefGoogle Scholar
  25. Meilhac O, Zhou M, Santanam N, Parthasarathy S (2000) J Lipid Res 41:1205–1213Google Scholar
  26. Nicholls DG (1976) FEBS Lett 61:103–110CrossRefGoogle Scholar
  27. Nishikawa T, Kukidome D, Sonoda K, Fujisawa K, Matsuhisa T, Motoshima H, Matsumura T, Araki E (2007) Diabetes Res Clin Pract 77:161–164CrossRefGoogle Scholar
  28. Reaven GM, Mondon CE, Chen YD, Breslow JL (1994) J Lipid Res 820–824.Google Scholar
  29. Rosen ED, Spiegelman BM (2006) Nature 444:847–853CrossRefGoogle Scholar
  30. Salerno AG, Silva TR, Amaral ME, Alberici LC, Bonfleur ML, Patrício PR, Francesconi EP, Grassi-Kassisse DM, Vercesi AE, Boschero AC, Oliveira HC (2007) Int J Obes (Lond) 31:1586–1595CrossRefGoogle Scholar
  31. Samartsev VN, Mokhova EN (1997) Biochem Mol Biol Int 42:29–34Google Scholar
  32. Schönfeld P, Wojtczak L (2008) Free Radic Biol Med 45:231–241CrossRefGoogle Scholar
  33. Schrauwen P, Hesselink MK (2004) Proc Nutr Soc 63:287–292CrossRefGoogle Scholar
  34. Skulachev VP (1991) FEBS Lett 294:158–162CrossRefGoogle Scholar
  35. Sperl W, Skladal D, Gnaiger E, Wyss M, Mayr U, Hager J, Gellerich FN (1997) Mol Cell Biochem 174:71–78CrossRefGoogle Scholar
  36. Vercesi AE, Martins IS, Silva MAP, Leite HMF, Cuccovia IM, Chaimovich H (1995) Nature 375:24CrossRefGoogle Scholar
  37. Zhang DX, Chen YF, Campbell WB, Zou AP, Gross GJ, Li PL (2001) Circ Res 89:1177–1183CrossRefGoogle Scholar
  38. Zhang CM, Gu Y, Qing DN, Zhu JG, Zhu C, Zhang M, Guo XR (2010) Mol Biol Rep 37:3177–3182CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Luciane C. Alberici
    • 1
  • Anibal E. Vercesi
    • 2
  • Helena C. F. Oliveira
    • 3
  1. 1.Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão PretoUniversidade de São PauloRibeirão PretoBrazil
  2. 2.Departamento de Patologia Clínica, Faculdade de Ciências MédicasUniversidade Estadual de CampinasCampinasBrazil
  3. 3.Departamento de Fisiologia e Biofísica, Instituto de BiologiaUniversidade Estadual de CampinasCampinasBrazil

Personalised recommendations