Mitochondrial adaptations to calorie restriction and bariatric surgery in human skeletal muscle: a systematic review with meta-analysis.

Objective: We performed a meta-analysis to determine the changes induced by calorie restriction (CR) and bariatric surgery on human skeletal muscle mitochondria.

Methods: A systematic search of Medline and Web of Science was conducted. Controlled trials exploring CR (≥14 days) and mitochondrial function and/or content assessment were included. Moreover, studies analyzing weight loss following gastric surgery were included for comparison purposes. Human muscle data from 28 studies assessing CR (520 muscle samples) and from 10 studies assessing bariatric surgery (155 muscle samples) were analyzed in a random effect meta-analysis with three a priori chosen covariates.

Main Results: We report a decrease (p < 0.05) (mean (95 % CI)) in maximal mitochondrial state 3 respiration in response to CR (-0.44 (-0.85, -0.03)) but not in response to surgery (-0.33 (-1.18, 0.52)). No changes in mitochondrial content were reported after CR (-0.05 (-0.12, 0.13)) or in response to surgery (0.23 (-0.05, 0.52)). Moreover, data from CR subjects showed a reduction in complex IV (CIV) activity (-0.29 (-0.56, -0.03)) but not in CIV content (-0.21 (-0.63, 0.22)). Similar results were obtained when the length of the protocol, the initial body mass index, and the estimated energy deficit were included in the model as covariates.

Conclusion: The observation of reduced maximal mitochondrial state 3, uncoupled respiration, and CIV activity without altering mitochondrial content suggests that, in human skeletal muscle, CR mainly modulates intrinsic mitochondrial function.