title: Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals.
abstract: The effects of caloric restriction (CR) on in vivo muscle mitochondrial function in humans are controversial.
  
  
  
  We evaluated muscle mitochondrial function and associated transcriptional profiles in nonobese humans after 12 months of CR.
  
  
  
  Individuals from an ancillary study of the CALERIE 2 randomized controlled trial were assessed at baseline and 12 months after a 25% CR or ad libitum (control) diet.
  
  
  
  The study was performed at Pennington Biomedical Research Center in Baton Rouge, LA.
  
  
  
  Study participants included 51 (34 female subjects, 25 to 50 years of age) healthy nonobese individuals randomized to 1 of 2 groups (CR or control).
  
  
  
  This study included 12 months of a 25% CR or ad libitum (control) diet.
  
  
  
  In vivo mitochondrial function [maximal ATP synthesis rate (ATPmax), ATPflux/O2 (P/O)] was determined by 31P-magnetic resonance spectroscopy and optical spectroscopy, and body composition was determined by dual-energy X-ray absorptiometry. In a subset of individuals, a muscle biopsy was performed for transcriptional profiling via quantitative reverse transcription polymerase chain reaction and microarrays.
  
  
  
  Weight, body mass index (BMI), fat, and fat-free mass (P < 0.001 for all) significantly decreased at month 12 after CR vs control. In vivo ATPmax and P/O were unaffected by 12 months of CR. Targeted transcriptional profiling showed no effects on pathways involved in mitochondrial biogenesis, function, or oxidative stress. A subgroup analysis according to baseline P/O demonstrated that a higher (vs lower) P/O was associated with notable improvements in ATPmax and P/O after CR.
  
  
  
  In healthy nonobese humans, CR has no effect on muscle mitochondrial function; however, having a "more coupled" (versus "less coupled") phenotype enables CR-induced improvements in muscle mitochondrial function.
authors: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida 32804.|Clinical and Molecular Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida 32827.
authors: Lauren M
authors: LM
authors: Sparks
authors: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808.
authors: Leanne M
authors: LM
authors: Redman
authors: Departments of Radiology.|Physiology & Biophysics, and.|Bioengineering, University of Washington Medical Center, Seattle, Washington 98195.
authors: Kevin E
authors: KE
authors: Conley
authors: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario ON K1N 6N5, Canada.
authors: Mary-Ellen
authors: ME
authors: Harper
authors: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida 32804.
authors: Fanchao
authors: F
authors: Yi
authors: Bioinformatics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037; and.
authors: Andrew
authors: A
authors: Hodges
authors: Bioinformatics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037; and.
authors: Alexey
authors: A
authors: Eroshkin
authors: Hospital for Sick Children, Toronto ON M5G 1X8, Canada.
authors: Sheila R
authors: SR
authors: Costford
authors: Clinical and Molecular Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida 32827.
authors: Meghan E
authors: ME
authors: Gabriel
authors: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida 32804.
authors: Cherie
authors: C
authors: Shook
authors: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida 32804.
authors: Heather H
authors: HH
authors: Cornnell
authors: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808.
authors: Eric
authors: E
authors: Ravussin
authors: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida 32804.|Clinical and Molecular Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida 32827.
authors: Steven R
authors: SR
authors: Smith
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight; D031204:Caloric Restriction; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress; D013997:Time Factors
chemical_list: D015415:Biomarkers