Hostname: page-component-76fb5796d-dfsvx Total loading time: 0 Render date: 2024-04-26T05:41:56.845Z Has data issue: false hasContentIssue false
  • English
  • Français

Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone

Published online by Cambridge University Press:  09 March 2007

Jean-François Dumas ,
Gilles Simard ,
Damien Roussel ,
Olivier Douay ,
Françoise Foussard ,
Yves Malthiery  and
Patrick Ritz
Jean-François Dumas
Affiliation:
Medecine B, CHU, F-49033 ANGERS Cedex 01, France
Gilles Simard
Affiliation:
Medecine B, CHU, F-49033 ANGERS Cedex 01, France
Damien Roussel
Affiliation:
Medecine B, CHU, F-49033 ANGERS Cedex 01, France
Olivier Douay
Affiliation:
Medecine B, CHU, F-49033 ANGERS Cedex 01, France
Françoise Foussard
Affiliation:
Medecine B, CHU, F-49033 ANGERS Cedex 01, France
Yves Malthiery
Affiliation:
Medecine B, CHU, F-49033 ANGERS Cedex 01, France
Patrick Ritz*
Affiliation:
Medecine B, CHU, F-49033 ANGERS Cedex 01, France
*
*Corresponding author: Professor Patrick Ritz, fax +33 241354969, email paritz@chu-angers.fr
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The present investigation was undertaken to evaluate whether mitochondrial energy metabolism is altered in a model of malnutrition induced by dexamethasone (DEX) treatment (1·5mg/kg per d for 5d). The gastrocnemius and liver mitochondria were isolated from DEX-treated, pair-fed (PF) and control (CON) rats. Body weight was reduced significantly more in the DEX-treated group (−16%) than in the PF group (−9%). DEX treatment increased liver mass (+59% v. PF, +23% v. CON) and decreased gastrocnemius mass. Moreover, in DEX-treated rats, liver mitochondria had an increased rate of non-phosphorylative O2 consumption with all substrates (approximately +42%). There was no difference in enzymatic complex activities in liver mitochondria between rat groups. Collectively, these results suggest an increased proton leak and/or redox slipping in the liver mitochondria of DEX-treated rats. In addition, DEX decreased the thermodynamic coupling and efficiency of oxidative phosphorylation. We therefore suggest that this increase in the proton leak and/or redox slip in the liver is responsible for the decrease in the thermodynamic efficiency of energy conversion. In contrast, none of the variables of energy metabolism determined in gastrocnemius mitochondria was altered by DEX treatment. Therefore, it appears that DEX specifically affects mitochondrial energy metabolism in the liver.

Keywords

GlucocorticoidMitochondrionOxidative phosphorylationRespiratory chain complexes
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 5 , November 2003 , pp. 969 - 977
Copyright
Copyright © The Nutrition Society 2003

References

Allan, EH, Chisholm, AB & Titheradge, MA (1983) The stimulation of hepatic oxidative phosphorylation following dexamethasone treatment of rats. Biochim Biophys Acta 725, 71–76.Google Scholar
Balsam, A & Ingbar, SH (1978) The influence of fasting, diabetes, and several pharmacological agents on the pathways of thyroxine metabolism in rat liver. J Clin Invest 62, 415–424.CrossRefGoogle ScholarPubMed
Bollen, M, Keppens, S & Stalmans, W (1998) Specific features of glycogen metabolism in the liver. Biochem J 336, 19–31.Google Scholar
Bowes, SB, Jackson, NC, Papachristodoulou, D, Umpleby, AM & Sonksen, PH (1996) Effect of corticosterone on protein degradation in isolated rat soleus and extensor digitorum longus muscles. J Endocrinol 148, 501–507.CrossRefGoogle ScholarPubMed
Brillon, DJ, Zheng, B, Campbell, RG & Matthews, DE (1995) Effect of cortisol on energy expenditure and amino acid metabolism in humans. Am J Physiol 268, E501–E513.Google Scholar
Cairns, CB, Walther, J, Harken, AH & Banerjee, A (1998) Mitochondrial oxidative phosphorylation thermodynamic efficiencies reflect physiological organ roles. Am J Physiol 274, R1376–R1383.Google Scholar
Capaccio, JA, Galassi, TM & Hickson, RC (1985) Unaltered aerobic power and endurance following glucocorticoid-induced muscle atrophy. Med Sci Sports Exerc 17, 380–384.CrossRefGoogle ScholarPubMed
Capitanio, N, Capitanio, GDe Nitto, E, Villani, G & Papa, S (1991) H+/e- stoichiometry of mitochondrial cytochrome complexes reconstituted in liposomes. Rate-dependent changes of the stoichiometry in the cytochrome c oxidase vesicles. FEBS Lett 288, 179–182.Google Scholar
Cassar-Malek, I, Kahl, S, Jurie, C & Picard, B (2001) Influence of feeding level during postweaning growth on circulating concentrations of thyroid hormones and extrathyroidal 5'-deiodination in steers. J Anim Sci 79, 2679–2687.Google Scholar
Chima, CS, Barco, K, Dewitt, ML, Maeda, M, Teran, JC & Mullen, KD (1997) Relationship of nutritional status to length of stay, hospital costs, and discharge status of patients hospitalized in the medicine service. J Am Diet Assoc 97, 975–978, 979–980.CrossRefGoogle ScholarPubMed
Chopra, IJ, Williams, DE, Orgiazzi, J & Solomon, DH (1975) Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3'5-triiodothyronine (T3). J Clin Endocrinol Metab 41, 911–920.Google Scholar
Dauncey, MJ (1990) Thyroid hormones and thermogenesis. Proc Nutr Soc 49, 203–215.Google Scholar
Franco-Colin, M, Tellez-Lopez, AM, Quevedo-Corona, L & Racotta, R (2000) Effects of long-term high-sucrose and dexamethasone on fat depots, liver fat, and lipid fuel fluxes through the retroperitoneal adipose tissue and splanchnic area in rats. Metabolism 49, 1289–1294.CrossRefGoogle ScholarPubMed
Hausberger, FX & Hausberger, BC (1958) Effect of insulin and cortisone on weight gain, protein and fat content of rats. Am J Physiol 103, 455–460.Google Scholar
Jani, MS, Telang, SD & Katyare, SS (1991) Effect of corticosterone treatment on energy metabolism in rat liver mitochondria. J Steroid Biochem Mol Biol 38, 587–591.Google Scholar
Kaplan, MM & Utiger, RD (1978) Iodothyronine metabolism in rat liver homogenates. J Clin Invest 61, 459–471.CrossRefGoogle ScholarPubMed
Kaur, N, Sharma, N & Gupta, AK (1989) Effects of dexamethasone on lipid metabolism in rat organs. Indian J Biochem Biophys 26, 371–376.Google Scholar
Kedem, O & Caplan, SR (1965) Degree of coupling and its relation to efficiency of energy conversion. Trans Faraday Soc 21, 1897–1911.CrossRefGoogle Scholar
Kerppola, W (1960) Uncoupling of the oxidative phosphorylation with cortisone in liver mitochondria. Endocrinology 67, 252–263.Google Scholar
Kimura, S & Rasmussen, H (1977) Adrenal glucocorticoids, adenine nucleotide translocation, and mitochondrial calcium accumulation. J Biol Chem 252, 1217–1225.Google Scholar
Kochakian, CD & Robertson, E (1951) Adrenal steroids and body composition. J Biol Chem 190, 495–503.Google Scholar
Koski, CL, Rifenberick, DH & Max, SR (1974) Oxidative metabolism of skeletal muscle in steroid atrophy. Arch Neurol 31, 407–410.Google Scholar
Krahenbuhl, S, Talos, C, Fischer, S & Reichen, J (1994) Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria. Hepatology 19, 471–479.Google ScholarPubMed
Landi, F, Onder, G, Gambassi, G, Pedone, C, Carbonin, P & Bernabei, R (2000) Body mass index and mortality among hospitalized patients. Arch Intern Med 160, 2641–2644.Google Scholar
Lesourd, B & Mazzari, L (1997) Immune responses during recovery from protein energy malnutrition. Clin Nutr 16, 37–46.CrossRefGoogle ScholarPubMed
Malgat, M, Durrieu, G & Mazat, JP (1999) Enzymatic and polarographic measurements of the respiratory chain complexes. In Mitochondrial Diseases, pp. 357–377 [Lestienne, P, editor]. Paris: Springer Verlag.Google Scholar
Marone, JR, Falduto, MT, Essig, DA & Hickson, RC (1994) Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle. J Appl Physiol 77, 1685–1690.Google Scholar
Max, SR, Mill, J, Mearow, K et al. (1988) Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles. Am J Physiol 255, E397–E402.Google ScholarPubMed
Mazzuccheli, MV, Confalonieri, C & Schlechter, P (1960) The nervous system and lipid metabolism of adipose tissue. 2. Influence of denervation on the lipogenetic activity of adrenocortical hormones. Metabolism 10, 330–334.Google Scholar
Michaels, JE & Cardell, RR (1997) Localization of glycogen phosphorylase activity in liver of fasted normal and adrenalectomized rats and in fasted adrenalectomized rats after injection of dexamethasone. Anat Rec 248, 406–412.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Minet-Quinard, R, Moinard, C, Villie, F et al. (1999) Kinetic impairment of nitrogen and muscle glutamine metabolisms in old glucocorticoid-treated rats. Am J Physiol 276, E558–E564.Google Scholar
Minet-Quinard, R, Moinard, C, Walrand, S et al. (2000) Induction of a catabolic state in rats by dexamethasone: dose or time dependency? J Parenter Enteral Nutr 24, 30–36.Google Scholar
Mitch, WE, Bailey, JL, Wang, X, Jurkovitz, C, Newby, D & Price, SR (1999) Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. Am J Physiol 276, C1132–C1138.CrossRefGoogle Scholar
Moriscot, A, Rabelo, R & Bianco, AC (1993) Corticosterone inhibits uncoupling protein gene expression in brown adipose tissue. Am J Physiol 265, E81–E87.Google Scholar
Nguyen, LT, Bedu, M, Caillaud, D et al. (1999) Increased resting energy expenditure is related to plasma TNF-alpha concentration in stable COPD patients. Clin Nutr 18, 269–274.Google Scholar
Nogueira, V, Rigoulet, M, Piquet, MA, Devin, A, Fontaine, E & Leverve, XM (2001) Mitochondrial respiratory chain adjustment to cellular energy demand. J Biol Chem 276, 46104–46110.CrossRefGoogle ScholarPubMed
Odedra, BR, Bates, PC & Millward, DJ (1983) Time course of the effect of catabolic doses of corticosterone on protein turnover in rat skeletal muscle and liver. Biochem J 214, 617–627.Google Scholar
Palacios, E, Pinon-Lopez, MJ, Racotta, IS & Racotta, R (1995) Effect of lipectomy and long-term dexamethasone on visceral fat and metabolic variables in rats. Metabolism 44, 1631–1638.Google Scholar
Papa, S, Capitanio, N, Capitanio, G, De Nitto, E & Minuto, M (1991) The cytochrome chain of mitochondria exhibits variable H+/e− stoichiometry. FEBS Lett 288, 183–186.Google Scholar
Ramsey, JJ, Harper, ME & Weindruch, R (2000) Restriction of energy intake, energy expenditure, and aging. Free Radic Biol Med 29, 946–968.Google Scholar
Rolfe, DF & Brown, GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77, 731–758.Google Scholar
Roussel, D, Dumas, JF, Augeraud, A et al. (2003) Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria. FEBS Lett 541, 75–79.Google Scholar
Roussel, D, Lhenry, F, Ecochard, L, Sempore, B, Rouanet, JL & Favier, R (2000) Differential effects of endurance training and creatine depletion on regional mitochondrial adaptations in rat skeletal muscle. Biochem J 350, 547–553.Google Scholar
Sato, K, Mimura, H, Han, DC, Tsushima, T & Shizume, K (1984) Ontogenesis of iodothyronine-5'-deiodinase. Induction of 5'-deiodinating activity by insulin, glucocorticoid, and thyroxine in cultured fetal mouse liver. J Clin Invest 74, 2254–2262.Google Scholar
Savary, I, Debras, E, Dardevet, D et al. (2001) Evidence for an alteration of plasma and liver proteins response to dexamethasone in aging rats. Mech Ageing Dev 122, 105–120.Google Scholar
Song, S & Oka, T (2003) Regulation of type II deiodinase expression by EGF and glucocorticoid in HC11 mouse mammary epithelium. Am J Physiol 284, E1119–E1124.Google Scholar
Strack, AM, Bradbury, MJ & Dallman, MF (1995) Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue. Am J Physiol 268, R183–R191.Google ScholarPubMed
Stucki, JW (1980) The optimal efficiency and the economic degrees of coupling of oxidative phosphorylation. Eur J Biochem 109, 269–283.Google Scholar
Tataranni, PA, Larson, DE, Snitker, S, Young, JB, Flatt, JP & Ravussin, E (1996) Effects of glucocorticoids on energy metabolism and food intake in humans. Am J Physiol 271, E317–E325.Google Scholar
Tiao, G, Fagan, J, Roegner, V et al. (1996) Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids. J Clin Invest 97, 339–348.CrossRefGoogle ScholarPubMed
Tokuyama, K & Himms-Hagen, J (1989) Enhanced acute response to corticosterone in genetically obese (ob/ob) mice. Am J Physiol 257, E133–E138.Google Scholar
Tucker, HN & Miguel, SG (1996) Cost containment through nutrition intervention. Nutr Rev 54, 111–121.CrossRefGoogle ScholarPubMed
Vignos, PJ & Greene, R (1973) Oxidative respiration of skeletal muscle in experimental corticosteroid myopathy. J Lab Clin Med 81, 365–378.Google Scholar
Wakat, DK & Haynes, RC Jr (1977) Glucocorticoid-stimulated utilization of substrates in hepatic mitochondria. Arch Biochem Biophys 184, 561–571.CrossRefGoogle ScholarPubMed
Wallace, JI, Schwartz, RS, LaCroix, AZ, Uhlmann, RF & Pearlman, RA (1995) Involuntary weight loss in older outpatients: incidence and clinical significance. J Am Geriatr Soc 43, 329–337.CrossRefGoogle ScholarPubMed
Weber, CA & Kletzien, RF (1982) Hormonal and nutritional factors influencing glycogen deposition in primary cultures of rat liver parenchymal cells. J Cell Physiol 110, 300–303.Google Scholar
Weber, K, Bruck, P, Mikes, Z, Kupper, JH, Klingenspor, M & Wiesner, RJ (2002) Glucocorticoid hormone stimulates mitochondrial biogenesis specifically in skeletal muscle. Endocrinology 143, 177–184.Google Scholar
Woodward, CJ & Emery, PW (1989) Energy balance in rats given chronic hormone treatment. 2. Effects of corticosterone. Br J Nutr 61, 445–452.Google Scholar