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European Journal of Nutrition

Erschienen in:

01.02.2016 | Review

A possible link between hepatic mitochondrial dysfunction and diet-induced insulin resistance

verfasst von: Raffaella Crescenzo, Francesca Bianco, Arianna Mazzoli, Antonia Giacco, Giovanna Liverini, Susanna Iossa

Erschienen in: European Journal of Nutrition | Ausgabe 1/2016

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Abstract

Background

Mitochondria are the main cellular sites devoted to ATP production and lipid oxidation. Therefore, the mitochondrial dysfunction could be an important determinant of cellular fate of circulating lipids, that accumulate in the cytoplasm, if they are not oxidized. The ectopic fat accumulation is associated with the development of insulin resistance, and a link between mitochondrial dysfunction and insulin resistance has been proposed.

Methods

Recent data on the possible link existing between mitochondrial dysfunction in the liver and diet-induced obesity will be summarized, focusing on the three factors that affect the mitochondrial oxidation of metabolic fuels, i.e. organelle number, organelle activity, and energetic efficiency of the mitochondrial machinery in synthesizing ATP. Search in PubMed relevant articles from 2003 to 2014 was conducted, by using query “liver mitochondria and obesity” “hepatic mitochondria and obesity” “liver mitochondria and high fat diet” and “hepatic mitochondria and high fat diet” and including related articles by the same groups.

Results

Several works, by using different physiological approaches, have dealt with alteration in mitochondrial function in obesity and diabetes. Most results show that hepatic mitochondrial function is impaired in models of obesity and insulin resistance induced by high-fat or high-fructose feeding.

Conclusions

Since mitochondria are the main producers of both cellular energy and free radicals, dysfunctional mitochondria could play an important role in the development of insulin resistance and ectopic fat storage in the liver, thus supporting the emerging idea that mitochondrial dysfunction is closely related to the development of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis.

Roden M (2006) Mechanisms of disease: hepatic steatosis in type 2 diabetes–pathogenesis and clinical relevance. Nature Clin Pract Endocrinol Metab 2:335–448CrossRef

Smith BW, Adams LA (2011) Non-alcoholic fatty liver disease. Crit Rev Clin Lab Sci 48:97–113CrossRef

Rolo AP, Teodoro JS, Palmeira CM (2012) Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med 52:59–69CrossRef

Szendroedi J, Roden M (2009) Ectopic lipids and organ function. Curr Opin Lipidol 20:50–56CrossRef

Takamura T, Misu H, Ota T, Kaneko S (2012) Fatty liver as a consequence and cause of insulin resistance: lessons from type 2 diabetic liver. Endocr J 59:745–763CrossRef

Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D et al (2004) Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279:32345–32353CrossRef

Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X et al (2011) Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci USA 108:16381–16385CrossRef

Jornayvaz FR, Shulman GI (2012) Diacylglycerol activation of protein kinase Cε and hepatic insulin resistance. Cell Metab 15:574–584CrossRef

Schmitz-Peiffer C, Biden TJ (2012) Protein kinase C function in muscle, liver, and beta-cells and its therapeutic implications for type 2 diabetes. Diabetes 57:1774–1783CrossRef

10.

Turner N, Heilbronn LK (2008) Is mitochondrial dysfunction a cause of insulin resistance? Trends Endocrinol Metab 19:324–330CrossRef

11.

Pessayre D, Fromenty B, Mansouri A (2004) Mitochondrial injury in steatohepatitis. Eur J Gastroenterol Hepatol 16:1095–1105CrossRef

12.

Pessayre D (2007) Role of mitochondria in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 22(Suppl 1):S20–S27CrossRef

13.

Silvestri E, Cioffi F, Glinni D, Ceccarelli M, Lombardi A, de Lange P et al (2010) Pathways affected by 3,5-diiodo-l-thyronine in liver of high fat-fed rats: evidence from two-dimensional electrophoresis, blue-native PAGE, and mass spectrometry. Mol BioSyst 6(11):2256–2271CrossRef

14.

de Lange P, Cioffi F, Senese R, Moreno M, Lombardi A, Silvestri E et al (2011) Nonthyrotoxic prevention of diet-induced insulin resistance by 3,5-diiodo-l-thyronine in rats. Diabetes 60(11):2730–2739CrossRef

15.

Pérez-Carreras M, Del Hoyo P, Martín MA, Rubio JC, Martín A, Castellano G et al (2003) Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 38:999–1007CrossRef

16.

Lockman KA, Nyirenda MJ (2010) Interrelationships between hepatic fat and insulin resistance in non-alcoholic fatty liver disease. Curr Diab Rev 6:341–347CrossRef

17.

Vial G, Dubouchaud H, Leverve XM (2010) Liver mitochondria and insulin resistance. Acta Biochim Pol 57:389–392

18.

Vial G, Dubouchaud H, Couturier K, Cottet-Rousselle C, Taleux C, Athias A et al (2011) Effects of a high-fat diet on energy metabolism and ROS production in rat liver. J Hepatol 54:348–356CrossRef

19.

Bouderba S, Sanz MN, Sánchez-Martín C, El-Mir MY, Villanueva GR, Detaille D et al (2012) Hepatic mitochondrial alterations and increased oxidative stress in nutritional diabetes-prone Psammomys obesus model. Exp Diab Res 2012:430176CrossRef

20.

Yu L, Fink BD, Herlein JA, Oltman CL, Lamping KG, Sivitz WI (2014) Dietary fat, fatty acid saturation and mitochondrial bioenergetics. J Bioenerg Biomembr 46(1):33–44CrossRef

21.

Satapati S, Sunny NE, Kucejova B, Fu X, He TT, Méndez-Lucas A et al (2012) Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver. J Lipid Res 53(6):1080–1092CrossRef

22.

Enos RT, Velázquez KT, Murphy EA (2014) Insight into the impact of dietary saturated fat on tissue-specific cellular processes underlying obesity-related diseases. J Nutr Biochem 25(6):600–612CrossRef

23.

Lieber CS, Leo MA, Mak KM, Xu Y, Cao Q, Ren C et al (2004) Model of nonalcoholic steatohepatitis. Am J Clin Nutr 79:502–509

24.

Kathirvel E, Morgan K, French SW, Morgan TR (2013) Acetyl-l-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. Nutr Res 33(11):932–941CrossRef

25.

Flamment M, Arvier M, Gallois Y, Simard G, Malthièry Y, Ritz P et al (2008) Fatty liver and insulin resistance in obese Zucker rats: no role for mitochondrial dysfunction. Biochimie 90:1407–1413CrossRef

26.

Buchner DA, Yazbek SN, Solinas P, Burrage LC, Morgan MG, Hoppel CL et al (2011) Increased mitochondrial oxidative phosphorylation in the liver is associated with obesity and insulin resistance. Obesity 19(5):917–924CrossRef

27.

Valdecantos MP, Pérez-Matute P, González-Muniesa P, Prieto-Hontoria PL, Moreno-Aliaga MJ, Martínez JA (2012) Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function. J Nutr Biochem 23:1676–1684CrossRef

28.

Flamment M, Rieusset J, Vidal H, Simard G, Malthièry Y, Fromenty B et al (2012) Regulation of hepatic mitochondrial metabolism in response to a high fat diet: a longitudinal study in rats. J Physiol Biochem 68:335–344CrossRef

29.

Nadal-Casellas A, Amengual-Cladera E, Proenza AM, Lladó I, Gianotti M (2010) Long-term high-fat-diet feeding impairs mitochondrial biogenesis in liver of male and female rats. Cell Physiol Biochem 26:291–302CrossRef

30.

Oliveira CP, Coelho AM, Barbeiro HV, Lima VM, Soriano F, Ribeiro C et al (2006) Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease. Braz J Med Biol Res 39:189–194

31.

Ciapaite J, Bakker SJ, Van Eikenhorst G, Wagner MJ, Teerlink T, Schalkwijk CG et al (2007) Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet fed rats. Biochim Biophys Acta 1772:307–316CrossRef

32.

Franko A, von Kleist-Retzow JC, Neschen S, Wu M, Schommers P, Böse M et al (2014) Liver adapts mitochondrial function to insulin resistant and diabetic states in mice. J Hepatol 60(4):816–823CrossRef

33.

Ciapaite J, van den Broek NM, Te Brinke H, Nicolay K, Jeneson JA, Houten SM et al (2011) Differential effects of short- and long-term high-fat diet feeding on hepatic fatty acid metabolism in rats. Biochim Biophys Acta 1811:441–451CrossRef

34.

Poussin C, Ibberson M, Hall D, Ding J, Soto J, Abel ED et al (2011) Oxidative phosphorylation flexibility in the liver of mice resistant to high-fat diet-induced hepatic steatosis. Diabetes 60(9):2216–2224CrossRef

35.

Mantena SK, Vaughn DP, Andringa KK, Eccleston HB, King AL, Abrams GA et al (2009) High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo. Biochem J 417(1):183–193CrossRef

36.

Teodoro JS, Duarte FV, Gomes AP, Varela AT, Peixoto FM, Rolo AP et al (2013) Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a possible role for SirT3 activation. Mitochondrion 13(6):637–646CrossRef

37.

Morris EM, Jackman MR, Meers GM, Johnson GC, Lopez JL, MacLean PS et al (2013) Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1α overexpression. Am J Physiol 305(11):G868–G880

38.

Lanni A, Moreno M, Lombardi A, de Lange P, Silvestri E, Ragni M et al (2005) 3,5-diiodo-l-thyronine powerfully reduces adiposity in rats by increasing the burning of fats. FASEB J 19(11):1552–1554

39.

Crescenzo R, Bianco F, Falcone I, Prisco M, Liverini G, Iossa S (2008) Alterations in hepatic mitochondrial compartment in a model of obesity and insulin resistance. Obesity 16:958–964CrossRef

40.

Carmiel-Haggai M, Cederbaum A, Nieto N (2005) A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J 19:136–138

41.

Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am J Physiol 292(2):C670–C686CrossRef

42.

Lee HC, Wei YH (2005) Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol 37:822–834CrossRef

43.

Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416:15–18CrossRef

44.

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

45.

Iossa S, Lionetti L, Mollica MP, Crescenzo R, Botta M, Barletta A et al (2003) Effect of high-fat feeding on metabolic efficiency and mitochondrial oxidative capacity in adult rats. Br J Nutr 90:953–960CrossRef

46.

Crescenzo R, Bianco F, Coppola P, Mazzoli A, Tussellino M, Carotenuto R et al (2014) Fructose supplementation worsens the deleterious effects of short-term high-fat feeding on hepatic steatosis and lipid metabolism in adult rats. Exp Physiol 99(9):1203–1213CrossRef

47.

Rector RS, Thyfault JP, Uptergrove GM, Morris EM, Naples SP, Borengasser SJ et al (2010) Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. J Hepatol 52(5):727–736CrossRef

48.

Bray GA (2010) Soft drink consumption and obesity: it is all about fructose. Curr Opin Lipidol 21:51–57CrossRef

49.

Tappy L, Lê KA (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90:23–46CrossRef

50.

Samuel VT (2011) Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab 22:60–65CrossRef

51.

Brown CM, Dulloo AG, Montani JP (2008) Sugary drinks in the pathogenesis of obesity and cardiovascular diseases. Int J Obes 32:S28–S34CrossRef

52.

Crescenzo R, Bianco F, Coppola P, Mazzoli A, Valiante S, Liverini G et al (2014) Adipose tissue remodeling in rats exhibiting fructose-induced obesity. Eur J Nutr 53:413–419CrossRef

53.

Crescenzo R, Bianco F, Coppola P, Mazzoli A, Cigliano L, Liverini G et al (2013) Increased skeletal muscle mitochondrial efficiency in rats with fructose-induced alteration in glucose tolerance. Br J Nutr 110:1996–2003CrossRef

54.

Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL et al (2009) Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 119(5):1322–1334CrossRef

55.

Cox CL, Stanhope KL, Schwarz JM, Graham JL, Hatcher B, Griffen SC et al (2011) Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women. Eur J Clin Nutr 66(2):201–208CrossRef

56.

Ren LP, Chan SM, Zeng XY, Laybutt DR, Iseli TJ, Sun RQ et al (2012) Differing endoplasmic reticulum stress response to excess lipogenesis versus lipid oversupply in relation to hepatic steatosis and insulin resistance. PLoS One 7(2):e30816. doi:10.1371/journal.pone.0030816 CrossRef

57.

Ferramosca A, Conte A, Damiano F, Siculella L, Zara V (2014) Differential effects of high-carbohydrate and high-fat diets on hepatic lipogenesis in rats. Eur J Nutr 53(4):1103–1114CrossRef

58.

Duarte JA, Carvalho F, Pearson M, Horton JD, Browning JD, Jones JG et al (2014) A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice. J Lipid Res 55(12):2541–2553CrossRef

59.

Chong MF, Hodson L, Bickerton AS, Roberts R, Neville M, Karpe F et al (2008) Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding. Am J Clin Nutr 87(4):817–823

60.

Feillet-Coudray C, Aoun M, Fouret G, Bonafos B, Ramos J, Casas F et al (2013) Effects of long-term administration of saturated and n-3 fatty acid-rich diets on lipid utilisation and oxidative stress in rat liver and muscle tissues. Br J Nutr 110(10):1789–1802CrossRef

61.

Morgan K, Uyuni A, Nandgiri G, Mao L, Castaneda L, Kathirvel E et al (2008) Altered expression of transcription factors and genes regulating lipogenesis in liver and adipose tissue of mice with high fat diet-induced obesity and nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 20(9):843–854CrossRef

62.

Oosterveer MH, van Dijk TH, Tietge UJ, Boer T, Havinga R, Stellaard F et al (2009) High fat feeding induces hepatic fatty acid elongation in mice. PLoS One 4(6):e6066. doi:10.1371/journal.pone.0006066 CrossRef

63.

de Meijer VE, Le HD, Meisel JA, Akhavan Sharif MR, Pan A, Nosé V et al (2010) Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine model. Metabolism 59(8):1092–1105CrossRef

64.

Crescenzo R, Bianco F, Falcone I, Coppola P, Liverini G, Iossa S (2013) Increased hepatic de novo lipogenesis and mitochondrial efficiency in a model of obesity induced by diets rich in fructose. Eur J Nutr 52:537–545CrossRef

65.

Castro MC, Francini F, Gagliardino JJ, Massa ML (2014) Lipoic acid prevents fructose-induced changes in liver carbohydrate metabolism: role of oxidative stress. Biochim Biophys Acta 1840:1145–1151CrossRef

66.

Castro MC, Massa ML, Shinella G, Gagliardino JJ, Francini F (2013) Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet. Biochim Biophys Acta 1830:2226–2232CrossRef

67.

Lambert K, Py G, Robert E, Mercier J (2003) Does high-sucrose diet alter skeletal muscle and liver mitochondrial respiration? Horm Metab Res 35:546–550CrossRef

Titel: A possible link between hepatic mitochondrial dysfunction and diet-induced insulin resistance
verfasst von: Raffaella Crescenzo
Francesca Bianco
Arianna Mazzoli
Antonia Giacco
Giovanna Liverini
Susanna Iossa
Publikationsdatum: 01.02.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 1/2016
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-015-1073-0

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A possible link between hepatic mitochondrial dysfunction and diet-induced insulin resistance

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