Relationships between mitochondrial content and bioenergetics with obesity, body composition and fat distribution in healthy older adults

Manish S Bharadwaj,J Jeffrey Carr,Mary F Lyles,Jamehl L Demons,Iris Leng,Anthony J A Molina,Daniel J Tyrrell,Barbara J Nicklas

doi:10.1186/s40608-015-0070-4

Manish S Bharadwaj, J Jeffrey Carr + Show 6 more

Open Access

https://doi.org/10.1186/s40608-015-0070-4

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Abstract

BackgroundMitochondrial function declines with age; however, the relationship between adiposity and mitochondrial function among older adults is unclear. This study examined relationships between skeletal muscle mitochondrial content and electron transport chain complex 2 driven respiration with whole body and thigh composition, body fat distribution, and insulin sensitivity in older adults.Methods25 healthy, sedentary, weight-stable men (N = 13) and women (N = 12) >65 years of age, with a BMI range of 18-35 kg/m2, participated in this study. Vastus lateralis biopsies were analyzed for citrate synthase (CS) activity and succinate mediated respiration of isolated mitochondria. Whole body and thigh composition were measured by DXA and CT. HOMA-IR was calculated using fasting glucose and insulin as an estimate of insulin sensitivity.ResultsSimilar to reports in middle-aged adults, skeletal muscle CS activity was negatively correlated with BMI (R = −0.43) in our cohort of older adults. Higher total and thigh adiposity were correlated with lower CS activity independent of BMI (R = −0.50 and −0.71 respectively). Maximal complex 2 driven mitochondrial respiration was negatively correlated with lower body adiposity in males (R = −0.66). In this cohort of non-diabetic older adults, both HOMA-IR and insulin were positively correlated with CS activity when controlling for BMI (R = 0.57 and 0.66 respectively).ConclusionsAdiposity and body composition are correlated with skeletal muscle mitochondrial content and electron transport chain function in healthy, sedentary, community dwelling, older adults. Specific relationships of mitochondrial bioenergetics with gender and insulin sensitivity are also apparent.Trial registrationClinicalTrials.gov identifier NCT01049698Electronic supplementary materialThe online version of this article (doi:10.1186/s40608-015-0070-4) contains supplementary material, which is available to authorized users.

Highlights

Mitochondrial function declines with age; the relationship between adiposity and mitochondrial function among older adults is unclear
We examined skeletal muscle bioenergetics in two ways; 1) citrate synthase (CS) activity, and 2) oxidative phosphorylation (OXPHOS) activity assessed by respirometric profiling of isolated organelles
Participant characteristics Body composition, body fat distribution, insulin and glucose, and bioenergetic profiles are presented in Table 1 for all participants and split by gender

Summary

Introduction

Mitochondrial function declines with age; the relationship between adiposity and mitochondrial function among older adults is unclear. This study examined relationships between skeletal muscle mitochondrial content and electron transport chain complex 2 driven respiration with whole body and thigh composition, body fat distribution, and insulin sensitivity in older adults. Bharadwaj et al BMC Obesity (2015) 2:40 differences in total and regional adiposity are likely underlying determinants of several deleterious changes in metabolic and physiologic function common with aging. Studies in middle-aged adults have reported that differences in body composition and insulin resistance have profound effects on skeletal muscle mitochondrial metabolism [18,19,20,21,22,23,24,25,26,27]. Among the bioenergetic differences linked to obesity and insulin resistance in these previous studies, oxidative phosphorylation (OXPHOS) activity and mitochondrial content have been reported to be significantly reduced

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