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

ABSTRACT: BACKGROUND:Mitochondrial 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. METHODS:25 healthy, sedentary, weight-stable men (N?=?13) and women (N?=?12) >65 years of age, with a BMI range of 18-35 kg/m(2), 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. RESULTS:Similar 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). CONCLUSIONS:Adiposity 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 REGISTRATION:ClinicalTrials.gov identifier NCT01049698.

SUBMITTER: Bharadwaj MS

PROVIDER: S-EPMC4594906 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Bharadwaj Manish S MS Tyrrell Daniel J DJ Leng Iris I Demons Jamehl L JL Lyles Mary F MF Carr J Jeffrey JJ Nicklas Barbara J BJ Molina Anthony J A AJ

BMC obesity 20151006

<h4>Background</h4>Mitochondrial 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.<h4>Methods</h4>25 healthy, sedentary, weight-stable men (N = 13) and women (N = 12) >65 years of ...[more]

PMID: 26448868

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Project description:BackgroundAdiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females.MethodsThirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses.ResultsMitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = - 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = - 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr.ConclusionsThese novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.

Project description:This study had two main objectives: To examine the association between body fat distribution and non-alcoholic fatty liver disease (NAFLD) and liver fat content, and to determine whether the relationship between NAFLD and regional body fat distribution, with respect to liver fat content in youths with excess adiposity, is independent of cardiorespiratory fitness (CRF) and a healthy diet. Liver fat content (controlled attenuation parameter (CAP)), body fat distribution (body mass index (BMI) z-score, waist circumference, waist-to-height ratio, fat mass/height, body fat percentage, total fat mass, android-to-gynoid fat mass ratio, visceral adipose tissue (VAT), and lean mass index, determined by dual-energy X-ray absorptiometry (DXA)), CRF (20-m shuttle-run test), and healthy diet (adherence to the Mediterranean diet by KIDMED questionnaire) were measured in 126 adolescents (66% girls) aged between 11 and 17 years. Participants were assigned to two groups according to the presence or absence of hepatic steatosis (CAP values ?225 dB/m or <225 dB/m of liver fat, respectively). Considering the similar total fat values for the two groups (>30% by DXA), youths with NAFLD had higher fat distribution parameters than those without NAFLD, regardless of sex, age, puberty stage, lean mass index, CRF, and healthy diet (p < 0.01). In the non-NAFLD group, the association between hepatic fat and fat distribution parameters presented a similar pattern, although the association was statistically insignificant after adjusting for a potential confounding variable (ps > 0.05), except for the case of VAT. Body fat distribution parameters were higher in youths with NAFLD compared to those without NAFLD. Additionally, body fat distribution showed a significant association with liver fat content as assessed by CAP in youths with NAFLD independent of CRF and adherence to the Mediterranean diet, supporting the notion that upper body fat distribution might play a pivotal role in the development of NAFLD in adolescents. These results may have implications for the clinical management of youths with excess adiposity given the high prevalence of NAFLD in children and young adults.

Project description:BackgroundAdipose tissue may have different metabolic and endocrine functions depending on the region of the body in which it is located. While visceral or intra-abdominal fat has been found to contribute to leptin concentrations, insulin resistance and obesity-related diseases, there are only a few imaging studies documenting the preferential distribution of body fat to either the intra-abdominal or subcutaneous compartments in dogs. This study aimed to determine if CT-measured abdominal fat distributed preferentially to the visceral space (V) relative to the subcutaneous space (SQ), with increasing DXA-determined total body fat percentage; and if ultrasound measurements of the ventral midline subcutaneous (SAT) and visceral adipose thickness (VAT) can be used to estimate the distribution of fat to the subcutaneous and visceral abdominal spaces, in a sample of 22 dogs with variable body condition.ResultsMultivariate analysis showed no statistically significant correlation between visceral to subcutaneous fat ratio (V/SQ) and increasing total body fat percentage (??=???0.07, p?=?0.733), but strong correlation with age (??=?0.71 p?=?0.002). A substantial amount of variation for the ultrasound visceral adipose thickness to subcutaneous fat thickness (VAT/SAT) could be explained by both CT V/SQ and sex (R2Adjusted?=?0.477, p?=?0.001), with female dogs having significant lower VAT/SAT ratios compared to the male dogs (p?=?0.047). The ultrasound fat measurements appeared moderately reliable, but a larger sample number is required to confirm this.ConclusionsThe findings suggest that dogs with a relatively healthy to slightly overweight body condition score, distribute fat relatively similarly between their peritoneal (visceral) and subcutaneous abdominal compartments with increasing total body fat percentage. However, there was increased fat distribution to the peritoneal space relative to the subcutaneous space with increasing age. Further, abdominal ultrasound may be useful in estimating the ratio of fat distribution to both the abdominal visceral and subcutaneous spaces.

Project description:Objective The observational studies indicate an association between obesity and epilepsy, but it is unclear whether such an association responds to causality. The objective of this study was to determine the causal relationship between obesity and fat distribution and epilepsy subtypes based on waist circumference, hip circumference (HP), waist-hip ratio (WHR), and body mass index (BMI). Methods A two-sample Mendelian randomization study was conducted separately for the four indicators of obesity and epilepsy and its seven subtypes, with reverse Mendelian randomization and multivariate Mendelian randomization for significant outcomes. Results A two-sample Mendelian randomized analysis informed us that waist circumference was a risk factor for juvenile myoclonic epilepsy (beta = 0.0299, P = 4.60 × 10−3). The increase in hip circumference increased the risk of juvenile myoclonic epilepsy and epilepsy, with effect values of 0.0283 (P = 2.01 × 10−3) and 0.0928 (P = 1.40 × 10−2), respectively. Furthermore, children with a higher BMI exhibit a higher risk of epilepsy (beta = 0.0148 P = 1.05 × 10−3). The reverse Mendelian randomization study revealed that childhood absence epilepsy increased its BMI (beta = 0.8980, P = 7.52 × 10−7), and juvenile myoclonic epilepsy increased its waist circumference (beta = 0.7322, P = 3.26 × 10−2). Multivariate Mendelian randomization revealed that an increase in hip circumference and waist-hip ratio increased the risk of juvenile myoclonic epilepsy, with an effect value of 0.1051 (P = 9.75 × 10−4) and 0.1430 (P = 3.99 × 10−3), respectively, while an increase in BMI and waist circumference instead decreased their risk, with effect values of −0.0951 (P = 3.14 × 10−2) and−0.0541 (P = 1.71 × 10−2). In contrast, multivariate Mendelian randomization for childhood absence epilepsy and epilepsy did not identify any independent risk factors. Significance Our findings provide novel evidence in favor of obesity as a risk factor for epilepsy and waist circumference as a risk factor for juvenile myoclonic epilepsy. Increased hip circumference confers an elevated risk of juvenile myoclonic epilepsy and epilepsy (all documented cases), and a high BMI increases the risk of childhood absence epilepsy. With this, new insights are provided into the energy metabolism of epilepsy, which supports further nutritional interventions and the search for new therapeutic targets.

Project description:Tetrahydrobiopterin (BH4) is an essential cofactor for several metabolic enzymes, including the aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and NO synthases. BH4 deficiency due to an autosomal recessive defect in its biosynthetic enzyme 6-pyruvoyltetrahydropterin synthase (PTPS, encoded by the PTS gene) leads to a variant form of hyperphenylalaninemia concomitant with severe deficiency of brain monoamine neurotransmitters. In contrast, augmentation of BH4 by pharmacological supplementation or stimulation of its biosynthesis is thought to correct eNOS dysfunction, to protect from (cardio) vascular disease and/or to prevent from abdominal obesity and development of the metabolic syndrome. We have previously reported that complete Pts knock-out (ko) mice die after birth (Elzaouk et al JBC 2003). Here we generated a murine Pts-knock-in (ki) allele expressing a PTPS-p.Arg15Cys mutant enzyme with low residual activity (12% of wild-type in vitro) and investigated heterozygous Pts-ko/wt, homozygous Pts-ki/ki and compound heterozygous Pts-ki/ko mutant mice. All mice were viable and, depending on the severity of the Pts alleles, exhibited up to 90% reduction of PTPS activity in liver and brain tissues concomitant with high neopterin, but neither an elevation of blood L-Phe, nor a decrease in brain monoamine neurotransmitters dopamine or serotonin. Upon a standard systemic and comprehensive phenotyping of Pts-ki/ki mice, we found alterations in energy metabolites with reduced body mass, higher fat content, lower lean mass, and increased blood glucose and cholesterol in mutant animals. Furthermore, heterozygous Pts-ko/wt and/or homozygous Pts-ki/ki mice exhibited increased body weight and elevated intra-abdominal fat tissue when fed with normal chow or high fat diet. We conclude that a reduced BH4-biosynthetic activity in mice leads to abnormal body fat distribution and abdominal obesity potentially through a mildly compromised eNOS function.

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

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

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