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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 2, February, 2002 239-245

Effect of Prolonged Undernutrition on Rat Diaphragm Mitochondrial Respiration

Stefan Matecki, Guillaume Py, Karen Lambert, Christelle Peyreigne, Jacques Mercier, Christian Prefaut, and Michele Ramonatxo

Laboratoire de Physiologie des Interactions, Service Central de Physiologie Clinique, Hôpital Arnaud de Villeneuve, Montpellier, France

Previous studies have shown that undernutrition induces an impairment of the respiratory muscle function in patients with chronic lung disease. To explain this, we hypothesized that undernutrition could decrease oxidative metabolism in the diaphragm. We therefore examined the effect of prolonged undernutrition on diaphragm mitochondrial oxygen uptake with pyruvate and palmitate as substrates in adult rats. Ten rats served as controls (CTL). Ten nutritionally deprived rats (ND) received 40% of their estimated daily nutrition. Five weeks of undernutrition induced a 33% decrease in state 3 respiration with pyruvate plus malate as substrate (993 ± 171 versus 1488 ± 167 nmol atomic O/mg/min, P < 0.01) and a 39% decrease with palmitate plus malate (516 ± 89 versus 850 ± 165 nmol atomic O/mg/min, P < 0.05). With succinate plus rotenone, there was no significant difference in the respiratory rate between groups. In the ND group, we found a significant decrease in citrate synthase activity (P < 0.01), and also in reduced nicotinamine adenine dinucleotide (NADH) dehydrogenase activity (P < 0.05), which cannot alone induce such a state 3 respiratory decrease. This showed that undernutrition in rat diaphragm does not induce an alteration in protein complexes I, II, III, and IV, or the F complex containing the mitochondrial ATPase of the electron transport chain. In conclusion, the main result of this study was that prolonged undernutrition induced a decrease in mitochondrial respiration secondary to a significant reduction in NADH generation by the Krebs cycle, which may affect respiratory muscle function with implications for patient care.

Abbreviations: controls, CTL; nutritionally deprived rats ND; reduce nicotinamine adenine dinucleotide, NADH; isolation medium, IM; proteinase medium, PM; respiratory medium, RM; respiratory control ratio, RCR; ratio of the amount of phosphorylated ADP to amount of oxygen, ADP/ O; Citrate synthase, CS; tris(hydroxymethyl)aminomethane, Tris; myosin heavy chain, MHC; ethylene glycol-bis(beta -aminoethyl ether)-N,N,N',N'- tetraacetic acid, EGTA.




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