Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans.

@article{citeulike:1185748, abstract = {BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y), overweight (body mass index, 27.8 +/- 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100\% of energy requirements; CR, 25\% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5\% CR + 12.5\% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35\% +/- 5\% in the CR group (p = 0.005) and 21\% +/- 4\% in the CREX group (p < 0.004), with no change in the control group (2\% +/- 2\%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003) and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR. CONCLUSIONS: The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults.}, author = {Civitarese, Anthony E E. and Carling, Stacy and Heilbronn, Leonie K K. and Hulver, Mathew H H. and Ukropcova, Barbara and Deutsch, Walter A A. and Smith, Steven R R. and Ravussin, Eric }, citeulike-article-id = {1185748}, doi = {10.1371/journal.pmed.0040076}, issn = {1549-1676}, journal = {PLoS Med}, keywords = {diet, mitochondria, mtdna}, month = {March}, number = {3}, posted-at = {2007-04-19 18:24:18}, priority = {2}, title = {Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans.}, url = {http://dx.doi.org/10.1371/journal.pmed.0040076}, volume = {4}, year = {2007} }

TY - JOUR ID - citeulike:1185748 L3 - citeulike-article-id:1185748 TI - Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans. JF - PLoS Med VL - 4 IS - 3 SN - 1549-1676 N2 - BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y), overweight (body mass index, 27.8 +/- 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005) and 21% +/- 4% in the CREX group (p < 0.004), with no change in the control group (2% +/- 2%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003) and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR. CONCLUSIONS: The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults. KW - diet KW - mitochondria KW - mtdna AU - Civitarese, Anthony E AU - Carling, Stacy AU - Heilbronn, Leonie K AU - Hulver, Mathew H AU - Ukropcova, Barbara AU - Deutsch, Walter A AU - Smith, Steven R AU - Ravussin, Eric PY - 2007/03/06/ UR - http://dx.doi.org/10.1371/journal.pmed.0040076 ER -