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

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

doi:10.1186/s40608-015-0070-4

Cited by 31 publications

(47 citation statements)

References 51 publications

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“…This is consistent with recent finding that increased adiposity is associated with decreased mitochondrial function from lower body skeletal muscle biopsies [23].…”

Section: Discussionsupporting

confidence: 93%

Monocyte bioenergetic function is associated with body composition in virologically suppressed HIV-infected women

et al. 2017

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Women living with HIV may present with high levels of body fat that are associated with altered bioenergetic function. Excess body fat may therefore exacerbate the bioenergetic dysfunction observed with HIV infection. To determine if body fat is associated with bioenergetic function in HIV, we conducted a cross-sectional study of 42 women with HIV who were virologically suppressed on antiretroviral therapy. Body composition was determined via dual-energy x-ray absorptiometry. Oxygen consumption rate (OCR) of monocytes was sorted from peripheral blood mononuclear cells obtained from participants in the fasting state. Differences in bioenergetic function, as measured by OCR, was assessed using Kruskal-Wallis tests and Spearman correlations adjusted for age, race, and smoking status. Participants were 86% Black, 45.5 years old, 48% current smokers, and 57% were obese (body mass index ≥30). Nearly all women (93%) had >30% total fat mass, while 12% had >50% total fat mass. Elevated levels of total fat mass, trunk fat, and leg fat were inversely correlated with measures of bioenergetic health as evidenced by lower maximal and reserve capacity OCR, and Bioenergetic Health Index. Measures of extracellular acidification (ECAR) in the absence (basal) or maximal (with oligomycin) were positively correlated with measures of bioenergetics, except proton leak, and were negatively correlated with fat mass. Despite virological suppression, women with HIV present with extremely high levels of adiposity that correlate with impaired bioenergetic health. Without effective interventions, this syndemic of HIV infection and obesity will likely have devastating consequences for our patients, potentially mediated through altered mitochondrial and glycolytic function.

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“…This is consistent with recent finding that increased adiposity is associated with decreased mitochondrial function from lower body skeletal muscle biopsies [23].…”

Section: Discussionsupporting

confidence: 93%

Monocyte bioenergetic function is associated with body composition in virologically suppressed HIV-infected women

et al. 2017

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“…Our study extends previous work showing that mitochondrial respiratory capacity and efficiency energetics were associated with walking speed in older adults . Our data also strengthen recent evidence indicating a positive association between mitochondrial content and insulin sensitivity in older individuals . Taken altogether, these results clearly emphasize the importance of mitochondria for skeletal muscle health and reinforce the view that mitochondria should be considered as important therapeutic targets to prevent or attenuate age‐related deterioration of muscle function and metabolism.…”

Section: Discussionsupporting

confidence: 90%

The impact of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men

St-Jean-Pelletier¹,

Pion

Leduc‐Gaudet³

et al. 2016

J cachexia sarcopenia muscle

115

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BackgroundThe exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men.MethodsRecreationally active young adult (20–30 yo; YA); active (ACT) and sedentary (SED) middle‐age (50–65 yo; MA‐ACT and MA‐SED); and older (65 + yo; 65 + ACT and 65 + SED) and pre‐frail older (65 + PF) men were recruited. Muscle biopsies from the vastus lateralis were collected to assess, on muscle cross sections, muscle phenotype (using myosin heavy chain isoforms immunolabelling), the fibre type‐specific content of mitochondria (by quantifying the succinate dehydrogenase stain intensity), and the fibre type‐specific lipid content (by quantifying the Oil Red O stain intensity).ResultsOnly 65 + SED and 65 + PF displayed significantly lower overall and type IIa fibre sizes vs. YA. 65 + SED displayed a lower type IIa fibre proportion vs. YA. MA‐SED and 65 + SED displayed a higher hybrid type IIa/IIx fibre proportion vs. YA. Sedentary and pre‐frail, but not active, men displayed lower mitochondrial content irrespective of fibre type vs. YA. 65 + SED, but not 65 + ACT, displayed a higher lipid content in type I fibres vs. YA. Finally, mitochondrial content, but not lipid content, was positively correlated with indices of muscle function, functional capacity, and insulin sensitivity across all subjects.ConclusionsTaken altogether, our results indicate that ageing in sedentary men is associated with (i) complex changes in muscle phenotype preferentially affecting type IIa fibres; (ii) a decline in mitochondrial content affecting all fibre types; and (iii) an increase in lipid content in type I fibres. They also indicate that physical activity partially protects from the effects of ageing on muscle phenotype, mitochondrial content, and lipid accumulation. No skeletal specific muscle phenotype of pre‐frailty was observed.

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“…Excess regional adipose tissue may impair skeletal muscle function and reduce mitochondrial density (42, 43); hence, the potential effects of obesity on skeletal muscle mitochondria are important to consider in the interpretation of the present results. While an earlier study has reported that Mfn2 mRNA is decreased in the skeletal muscle of obese individuals (44), a more recent study has shown that protein content of Mfn2 is unaffected (45).…”

Section: Discussionmentioning

confidence: 99%

Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance

Molina

Bharadwaj

Horn

et al. 2016

JACC: Heart Failure

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141

114

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Objectives The aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart failure with preserved ejection fraction (HFpEF) and to determine potential relationships with measures of exercise performance. Background Multiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2) in older patients with HFpEF, is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism, however little is known about how these organelles are affected in HFpEF. Methods Vastus lateralis skeletal muscle citrate synthase activity, and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n=20) and healthy, age-matched controls (n=17). Results In HFpEF patients compared to age-matched healthy controls, mitochondrial content assessed by Porin expression was 46% lower (p-value= 0.01), citrate synthase activity was 29% lower (p= 0.01), and Mfn2 expression was 54% lower (p= <0.001). Expression of Porin was significantly positively correlated with both peak VO2 and 6 minute walk distance (r=0.48, p=0.003 and r=0.33, p=0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6 minute walk distance (r=0.40, p=0.02 and r=0.37, p=0.03 respectively). Conclusion These findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and may contribute to their severe exercise intolerance.

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

Cited by 31 publications

References 51 publications

Monocyte bioenergetic function is associated with body composition in virologically suppressed HIV-infected women

Monocyte bioenergetic function is associated with body composition in virologically suppressed HIV-infected women

The impact of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men

Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance

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