Effect of Prolonged Undernutrition on Rat Diaphragm Mitochondrial Respiration

Abstract

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.

Hypoxia-inducible Factor 2α Regulates Expression of the Mitochondrial Aconitase Chaperone Protein Frataxin

“…Previous studies of Epas1 Ϫ/Ϫ mice revealed an in vivo role for HIF-2␣ in the regulation of several major antioxidant enzyme genes, including Sod2 (17 (52,53) and metabolic capacity (54), is lower for complex I-linked substrates, and RCRs are lower for both complex I-as well as complex II-linked substrates in Epas1 Ϫ/Ϫ liver mitochondria. Similar patterns of mitochondrial respiration were observed in Sod2 ϩ/Ϫ (22) and Sod2 Ϫ/Ϫ (24) liver mitochondria.…”

Age-related decrease in aromatase and estrogen receptor (ERα and ERβ) expression in rat testes: protective effect of low caloric diets

“…Male Wistar rats, aged from 2 to 18 months, were either fed ad libitum (control) or submitted to diets of caloric restriction (CR1) or undernutrition (CR2), as reported elsewhere [8,9]. The CR1 and CR2 groups received, respectively, 60% and 40% of the quantity of food given to the control rats (equivalent to 413 kCal/kg body weight/day) and the restriction was initiated in animals aged 4 weeks.…”

Automated detection and delineation of mitochondria in electron micrographs of human skeletal muscles

“…The morphometry of the mitochondria reveals physiological information relating to exercise history (Manfredi et al, 1991;Mayne et al, 1991;Roth et al, 2000;Santoro et al, 2002;Singh et al, 1999), nutrition history (Matecki et al, 2002;Stockwell, 1991), and aging (Bechman and Ames, 1998;Kayar et al, 1988). Athletes competing in endurance sports such as marathon runners frequently exhibit a greater capacity for aerobic energy production, as evidenced by the increased volume of mitochondria and lipids in both slowtwitch and fast-twitch muscle fibers (Friden and Lieber, 1992).…”