EFFECTS OF 12 MONTHS OF CALORIC RESTRICTION ON MUSCLE MITOCHONDRIAL FUNCTION IN HEALTHY INDIVIDUALS
Open accessAbstract
Context: The effects of caloric restriction (CR) on in vivo muscle mitochondrial function in humans are controversial. Objective: We evaluated muscle mitochondrial function and associated transcriptional profiles in nonobese humans after 12 months of CR. Design: 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. Setting: The study was performed at Pennington Biomedical Research Center in Baton Rouge, LA. Participants: 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). Intervention: This study included 12 months of a 25% CR or ad libitum (control) diet. Main Outcomes: 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. Results: 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. Conclusions: 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.
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Caloric restriction remodeling makes mitochondria more efficient, with an increased proportion of respiration coupled to ATP production and reduced overall oxygen consumption and ROS production.
“This remodeling makes mitochondria more efficient – increased proportion of respiration coupled to ATP production and reduced overall oxygen consumption and producing less ROS [71]”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [71]
In the Sparks et al. (2016) study, there was no change in mitochondrial capacity (ATPmax), coupling efficiency (P/O ratio), or mRNA levels of markers of mitochondrial biogenesis.
“However, there was no change in mitochondrial capacity as measured by ATPmax, or in coupling efficiency as measured by the P/O ratio, or in mRNA levels of markers of mitochondrial biogenesis.”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Sparks et al. (2016)
Individuals who had a more coupled phenotype at baseline were able to better improve mitochondrial function in response to CR.
“Contrary to expectations, individuals who had a more coupled phenotype at baseline were able to better improve mitochondrial function in response to CR.”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Sparks et al. (2016)
In 51 overweight but not obese individuals, 12 months of 25% CR vs control reduced intramyocellular lipid in soleus and mRNA levels of genes involved in lipogenesis and lipid transport.
“In this study, CR reduced intramyocellular lipid in soleus, and mRNA levels of genes involved in lipogenesis and lipid transport.”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Sparks et al. (2016)
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- Authors
- Sparks, L. M., Redman, L. M., Conley, K. E., Harper, M.-E., Yi, F., Hodges, A., Eroshkin, A., Costford, S. R., Gabriel, M. E., Shook, C., Cornnell, H. H., Ravussin, E., & Smith, S. R.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Pennington Biomedical Research Center (US)
- University of Washington Medical Center (US)
- University of Ottawa (CA)
- Translational Research Institute for Metabolism and Diabetes (US)
- Hospital for Sick Children (CA)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-10-25
- Volume
- 102
- Issue
- 1
- Pages
- jc.2016-3211
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5413108
- OpenAlex
- W2532998048
- Cited by
- 45
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 10 · 2019: 4 · 2018: 2 · 2017: 5
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- University of California
- National Institute on Aging (U01AG020478, R01AG030226)
- National Institute of General Medical Sciences (U54GM104940)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072476)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- caloric restriction, skeletal muscle, ATP production, P/O ratio, mitochondrial biogenesis, oxidative stress, gene expression, body composition, fat-free mass
- MeSH terms
- Adult, Body Composition, Body Weight, Energy Metabolism, Female, Humans, Male, Middle Aged, Mitochondria, Muscle, Time Factors, Biomarkers, Exercise, Body Mass Index, Oxidative Stress, Muscle, Skeletal, Gene Expression Profiling, Caloric Restriction, Healthy Volunteers
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