A Possible Link Between Hepatic Mitochondrial Dysfunction and Diet-induced Insulin Resistance

Overview

Journal Eur J Nutr

Specialty Nutritional Sciences

Date 2015 Oct 19

PMID 26476631

Citations 21

Authors

Raffaella Crescenzo

Francesca Bianco

Arianna Mazzoli

Antonia Giacco

Giovanna Liverini

Susanna Iossa

Affiliations

Soon will be listed here.

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 highfructose 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.

Citing Articles

An E115A Missense Variant in CERS2 Is Associated With Increased Sleeping Energy Expenditure and Hepatic Insulin Resistance in American Indians.

Heinitz S, Traurig M, Krakoff J, Rabe P, Staubert C, Kobes S Diabetes. 2024; 73(8):1361-1371.

PMID: 38776413 PMC: 11262042. DOI: 10.2337/db23-0690.

Mitochondria as a target for exercise-mitigated type 2 diabetes.

Tian J, Fan J, Zhang T J Mol Histol. 2023; 54(6):543-557.

PMID: 37874501 DOI: 10.1007/s10735-023-10158-1.

Recent Overview of Potent Antioxidant Activity of Coordination Compounds.

Abd El-Lateef H, El-Dabea T, Khalaf M, M Abu-Dief A Antioxidants (Basel). 2023; 12(2).

PMID: 36829772 PMC: 9952845. DOI: 10.3390/antiox12020213.

Berberine mitigates hepatic insulin resistance by enhancing mitochondrial architecture via the SIRT1/Opa1 signalling pathway.

Xu J, Zhang Y, Yu Z, Guan Y, Lv Y, Zhang M Acta Biochim Biophys Sin (Shanghai). 2022; 54(10):1464-1475.

PMID: 36269134 PMC: 9827808. DOI: 10.3724/abbs.2022146.

Time-of-Day Circadian Modulation of Grape-Seed Procyanidin Extract (GSPE) in Hepatic Mitochondrial Dynamics in Cafeteria-Diet-Induced Obese Rats.

Rodriguez R, Cortes-Espinar A, Soliz-Rueda J, Feillet-Coudray C, Casas F, Colom-Pellicer M Nutrients. 2022; 14(4).

PMID: 35215423 PMC: 8876123. DOI: 10.3390/nu14040774.

References

Jornayvaz F, Shulman G . Diacylglycerol activation of protein kinase Cε and hepatic insulin resistance. Cell Metab. 2012; 15(5):574-84. PMC: 3353749. DOI: 10.1016/j.cmet.2012.03.005. View

Pessayre D, Fromenty B, Mansouri A . Mitochondrial injury in steatohepatitis. Eur J Gastroenterol Hepatol. 2004; 16(11):1095-105. DOI: 10.1097/00042737-200411000-00003. View

Crescenzo R, Bianco F, Coppola P, Mazzoli A, Cigliano L, Liverini G . Increased skeletal muscle mitochondrial efficiency in rats with fructose-induced alteration in glucose tolerance. Br J Nutr. 2013; 110(11):1996-2003. DOI: 10.1017/S0007114513001566. View

Tappy L, Le K . Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev. 2010; 90(1):23-46. DOI: 10.1152/physrev.00019.2009. View

Valdecantos M, Perez-Matute P, Gonzalez-Muniesa P, Prieto-Hontoria P, Moreno-Aliaga M, Martinez J . Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function. J Nutr Biochem. 2012; 23(12):1676-84. DOI: 10.1016/j.jnutbio.2011.11.011. View

Crescenzo R, Bianco F, Coppola P, Mazzoli A, Tussellino M, Carotenuto R . Fructose supplementation worsens the deleterious effects of short-term high-fat feeding on hepatic steatosis and lipid metabolism in adult rats. Exp Physiol. 2014; 99(9):1203-13. DOI: 10.1113/expphysiol.2014.079632. View

Carmiel-Haggai M, Cederbaum A, Nieto N . A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J. 2004; 19(1):136-8. DOI: 10.1096/fj.04-2291fje. View

Enos R, Velazquez K, Murphy E . Insight into the impact of dietary saturated fat on tissue-specific cellular processes underlying obesity-related diseases. J Nutr Biochem. 2014; 25(6):600-12. PMC: 4419731. DOI: 10.1016/j.jnutbio.2014.01.011. View

Lanni A, Moreno M, Lombardi A, de Lange P, Silvestri E, Ragni M . 3,5-diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats. FASEB J. 2005; 19(11):1552-4. DOI: 10.1096/fj.05-3977fje. View

10.

Morgan K, Uyuni A, Nandgiri G, Mao L, Castaneda L, Kathirvel E . 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. 2008; 20(9):843-54. DOI: 10.1097/MEG.0b013e3282f9b203. View

11.

Bray G . Soft drink consumption and obesity: it is all about fructose. Curr Opin Lipidol. 2009; 21(1):51-7. DOI: 10.1097/MOL.0b013e3283346ca2. View

12.

Castro M, Massa M, Schinella G, Gagliardino J, Francini F . Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet. Biochim Biophys Acta. 2012; 1830(1):2226-32. DOI: 10.1016/j.bbagen.2012.10.010. View

13.

Schmitz-Peiffer C, Biden T . Protein kinase C function in muscle, liver, and beta-cells and its therapeutic implications for type 2 diabetes. Diabetes. 2008; 57(7):1774-83. PMC: 2453608. DOI: 10.2337/db07-1769. View

14.

Kathirvel E, Morgan K, French S, Morgan T . 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. 2013; 33(11):932-41. DOI: 10.1016/j.nutres.2013.08.001. View

15.

Roden M . Mechanisms of Disease: hepatic steatosis in type 2 diabetes--pathogenesis and clinical relevance. Nat Clin Pract Endocrinol Metab. 2006; 2(6):335-48. DOI: 10.1038/ncpendmet0190. View

16.

Lambert K, Py G, Robert E, Mercier J . Does high-sucrose diet alter skeletal muscle and liver mitochondrial respiration?. Horm Metab Res. 2003; 35(9):546-50. DOI: 10.1055/s-2003-42657. View

17.

Teodoro J, Duarte F, Gomes A, Varela A, Peixoto F, Rolo A . Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a possible role for SirT3 activation. Mitochondrion. 2013; 13(6):637-46. DOI: 10.1016/j.mito.2013.09.002. View

18.

Samuel V, Liu Z, Qu X, Elder B, Bilz S, Befroy D . Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem. 2004; 279(31):32345-53. DOI: 10.1074/jbc.M313478200. View

19.

Crescenzo R, Bianco F, Falcone I, Coppola P, Liverini G, Iossa S . Increased hepatic de novo lipogenesis and mitochondrial efficiency in a model of obesity induced by diets rich in fructose. Eur J Nutr. 2012; 52(2):537-45. DOI: 10.1007/s00394-012-0356-y. View

20.

Ciapaite J, Bakker S, van Eikenhorst G, Wagner M, Teerlink T, Schalkwijk C . Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet fed rats. Biochim Biophys Acta. 2006; 1772(3):307-16. DOI: 10.1016/j.bbadis.2006.10.018. View