Preferences help
enabled [disable] Abstract
Number of results
2010 | 57 | 4 | 389-392
Article title

Liver mitochondria and insulin resistance

Title variants
Languages of publication
With a steadily increasing prevalence, insulin resistance (IR) is a major public health issue. This syndrome is defined as a set of metabolic dysfunctions associated with, or contributing to, a range of serious health problems. These disorders include type 2 diabetes, metabolic syndrome, obesity, and non-alcoholic steatohepatitis (NASH). According to the literature in the field, several cell types like β-cell, myocyte, hepatocyte and/or adipocyte, as well as related complex signaling environment involved in peripheral insulin sensitivity are believed to be central in this pathology. Because of the central role of the liver in the whole-body energy homeostasis, liver insulin sensitivity and its potential relationship with mitochondrial oxidative phosphorylation appear to be crucial. The following short review highlights how liver mitochondria could be implicated in IR and should therefore be considered as a specific therapeutic target in the future.
Physical description
  • Inserm, Grenoble, France
  • Inserm, Grenoble, France
  • Inserm, Grenoble, France
  • Brady LJ, Brady PS, Romsos DR, Hoppel CL (1985) Elevated hepatic mitochondrial and peroxisomal oxidative capacities in fed and starved adult obese (ob/ob) mice. Biochem J 231: 439-444.
  • Brand MD (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35: 811-820.
  • Chavin KD, Yang S, Lin HZ, Chatham J, Chacko VP, Hoek JB, Walajtys-Rode E, Rashid A, Chen CH, Huang CC, Wu TC, Lane MD, Diehl AM (1999) Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J Biol Chem 274: 5692-5700.
  • Cook GA, Gamble MS (1987) Regulation of carnitine palmitoyltransferase by insulin results in decreased activity and decreased apparent Ki values for malonyl-CoA. J Biol Chem 262: 2050-2055.
  • Kim JA, Wei Y, Sowers JR (2008) Role of mitochondrial dysfunction in insulin resistance. Circ Res 102: 401-414.
  • Kraegen EW, Clark PW, Jenkins AB, Daley EA, Chisholm DJ, Storlien LH (1991) Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes 40: 1397-1403.
  • Leverve XM, Fontaine E (2001) Role of substrates in the regulation of mitochondrial function in situ. IUBMB Life 52: 221-229.
  • Lieber CS, Leo MA, Mak KM, Xu Y, Cao Q, Ren C, Ponomarenko A, DeCarli LM (2004) Model of nonalcoholic steatohepatitis. Am J Clin Nutr 79: 502-509.
  • Mollica MP, Lionetti L, Moreno M, Lombardi A, De Lange P, Antonelli A, Lanni A, Cavaliere G, Barletta A, Goglia F (2009) 3,5-diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet. J Hepatol 51: 363-370.
  • Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI (2005) Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 115: 3587-3593.
  • Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR, Mandarino LJ (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100: 8466-8471.
  • Perez-Carreras M, Del Hoyo P, Martin MA, Rubio JC, Martin A, Castellano G, Colina F, Arenas J, Solis-Herruzo JA (2003) Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 38: 999-1007.
  • Pessayre D (2007) Role of mitochondria in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 22 (Suppl 1): S20-27.
  • Pessayre D, Fromenty B, Mansouri A (2004) Mitochondrial injury in steatohepatitis. Eur J Gastroenterol Hepatol 16: 1095-1105.
  • Raffaella C, Francesca B, Italia F, Marina P, Giovanna L, Susanna I (2008) Alterations in hepatic mitochondrial compartment in a model of obesity and insulin resistance. Obesity (Silver Spring) 16: 958-964.
  • Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI (2004) Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279: 32345-32353.
  • Serviddio G, Bellanti F, Tamborra R, Rollo T, Capitanio N, Romano AD, Sastre J, Vendemiale G, Altomare E (2008) Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury. Gut 57: 957-965.
  • Speakman JR, Talbot DA, Selman C, Snart S, McLaren JS, Redman P, Krol E, Jackson DM, Johnson MS, Brand MD (2004) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3: 87-89.
  • Takamura T, Misu H, Matsuzawa-Nagata N, Sakurai M, Ota T, Shimizu A, Kurita S, Takeshita Y, Ando H, Honda M, Kaneko S (2008) Obesity upregulates genes involved in oxidative phosphorylation in livers of diabetic patients. Obesity (Silver Spring) 16: 2601-2609.
  • Taleux N, Guigas B, Dubouchaud H, Moreno M, Weitzel JM, Goglia F, Favier R, Leverve XM (2009) High expression of thyroid hormone receptors and mitochondrial glycerol-3-phosphate dehydrogenase in the liver is linked to enhanced fatty acid oxidation in Lou/C, a rat strain resistant to obesity. J Biol Chem 284: 4308-4316.
  • Vial G, Dubouchaud H, Couturier K, Cottet-Rousselle C, Taleux N, Athias A, Galinier A, Casteilla L, Leverve X (2010) Effects of a high-fat diet on energy metabolism and ROS production in rat liver. J Hepatol. doi:10.1016/j.hep.2010.06.044.
  • Zhang D, Liu ZX, Choi CS, Tian L, Kibbey R, Dong J, Cline GW, Wood PA, Shulman GI (2007) Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proc Natl Acad Sci USA 104: 17075-17080.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.