Lauren M Sparks1, Leanne M Redman1, Kevin E Conley1, Mary-Ellen Harper1, Andrew Hodges1, Alexey Eroshkin1, Sheila R Costford1, Meghan E Gabriel1, Fanchao Yi1, Cherie Shook1, Heather H Cornnell1, Eric Ravussin1, Steven R Smith1. 1. Translational Research Institute for Metabolism and Diabetes (L.M.S., F.Y., C.S., H.H.C., S.R.S.), Florida Hospital, Orlando, Florida 32804; Clinical and Molecular Origins of Disease (L.M.S., M.E.G., S.R.S.), Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida 32827; Pennington Biomedical Research Center (L.M.R., E.R.), Louisiana State University System, Baton Rouge, Louisiana 70808; Departments of Radiology, Physiology and Biophysics, and Bioengineering (K.E.C.), University of Washington Medical Center, Seattle, Washington 98195; Department of Biochemistry, Microbiology, and Immunology (M.-E.H.), University of Ottawa, Ottawa, Ontario ON K1N 6N5, Canada; Bioinformatics Core (A.H., A.E.), Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037; and Hospital for Sick Children (S.R.C.), Toronto, Ontario, ON M5G 1X8 Canada.
Abstract
CONTEXT: Reduced mitochondrial coupling (ATP/O2 [P/O]) is associated with sedentariness and insulin resistance. Interpreting the physiological relevance of P/O measured in vitro is challenging. OBJECTIVE: To evaluate muscle mitochondrial function and associated transcriptional profiles in nonobese healthy individuals distinguished by their in vivo P/O. DESIGN: Individuals from an ancillary study of Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy phase 2 were assessed at baseline. SETTING: The study was performed at Pennington Biomedical Research Center. PARTICIPANTS: Forty-seven (18 males, 26-50 y of age) sedentary, healthy nonobese individuals were divided into 2 groups based on their in vivo P/O. INTERVENTION: None. Main Outcome(s): Body composition by dual-energy x-ray absorptiometry, in vivo mitochondrial function (P/O and maximal ATP synthetic capacity) by 31P-magnetic resonance spectroscopy and optical spectroscopy were measured. A muscle biopsy was performed to measure fiber type, transcriptional profiling (microarray), and protein expressions. RESULTS: No differences in body composition, peak aerobic capacity, type I fiber content, or mitochondrial DNA copy number were observed between the 2 groups. Compared with the uncoupled group (lower P/O), the coupled group (higher P/O) had higher rates of maximal ATP synthetic capacity (maximal ATP synthetic capacity, P < .01). Transcriptomics analyses revealed higher expressions of genes involved in mitochondrial remodeling and the oxidative stress response in the coupled group. A trend for higher mitonuclear protein imbalance (P = .06) and an elevated mitochondrial unfolded protein response (heat shock protein 60 protein; P = .004) were also identified in the coupled group. CONCLUSIONS: Higher muscle mitochondrial coupling is accompanied by an overall elevation in mitochondrial function, a novel transcriptional signature of oxidative stress and mitochondrial remodeling and indications of an mitochondrial unfolded protein response.
RCT Entities:
CONTEXT: Reduced mitochondrial coupling (ATP/O2 [P/O]) is associated with sedentariness and insulin resistance. Interpreting the physiological relevance of P/O measured in vitro is challenging. OBJECTIVE: To evaluate muscle mitochondrial function and associated transcriptional profiles in nonobese healthy individuals distinguished by their in vivo P/O. DESIGN: Individuals from an ancillary study of Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy phase 2 were assessed at baseline. SETTING: The study was performed at Pennington Biomedical Research Center. PARTICIPANTS: Forty-seven (18 males, 26-50 y of age) sedentary, healthy nonobese individuals were divided into 2 groups based on their in vivo P/O. INTERVENTION: None. Main Outcome(s): Body composition by dual-energy x-ray absorptiometry, in vivo mitochondrial function (P/O and maximal ATP synthetic capacity) by 31P-magnetic resonance spectroscopy and optical spectroscopy were measured. A muscle biopsy was performed to measure fiber type, transcriptional profiling (microarray), and protein expressions. RESULTS: No differences in body composition, peak aerobic capacity, type I fiber content, or mitochondrial DNA copy number were observed between the 2 groups. Compared with the uncoupled group (lower P/O), the coupled group (higher P/O) had higher rates of maximal ATP synthetic capacity (maximal ATP synthetic capacity, P < .01). Transcriptomics analyses revealed higher expressions of genes involved in mitochondrial remodeling and the oxidative stress response in the coupled group. A trend for higher mitonuclear protein imbalance (P = .06) and an elevated mitochondrial unfolded protein response (heat shock protein 60 protein; P = .004) were also identified in the coupled group. CONCLUSIONS: Higher muscle mitochondrial coupling is accompanied by an overall elevation in mitochondrial function, a novel transcriptional signature of oxidative stress and mitochondrial remodeling and indications of an mitochondrial unfolded protein response.
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Authors: Lauren M Sparks; Leanne M Redman; Kevin E Conley; Mary-Ellen Harper; Fanchao Yi; Andrew Hodges; Alexey Eroshkin; Sheila R Costford; Meghan E Gabriel; Cherie Shook; Heather H Cornnell; Eric Ravussin; Steven R Smith Journal: J Clin Endocrinol Metab Date: 2017-01-01 Impact factor: 5.958