Wake Forest, NC, United States
Wake Forest, NC, United States

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Kavanagh K.,Wake forest University | Davis A.T.,Wake forest University | Peters D.E.,Wake forest University | Legrand A.C.,Wake forest University | And 2 more authors.
Obesity | Year: 2017

Objective: Obesity exists with and without accompanying cardiometabolic disease, termed metabolically unhealthy obesity (MUO) and healthy obesity (MHO), respectively. Underlying differences in the ability of subcutaneous (SQ) fat to respond to nutrient excess are emerging as a key pathway. This study aimed to document the first spontaneous animal model of MHO and MUO and differences in SQ adipose tissue. Methods: Vervet monkeys (Chlorocebus aethiops; N=171) were screened for metabolic syndrome. A subset of MHO and MUO monkeys (n=6/group) had SQ fat biopsies collected for histological evaluations and examination of key mitochondrial proteins. Results: Obesity was seen in 20% of monkeys, and within this population, 31% were healthy, which mirrors human prevalence estimates. MUO monkeys had more than 60% lower adiponectin concentrations despite similar fat cell size, uncoupling protein 3, and activated macrophage abundance. However, alternatively activated/anti-inflammatory macrophages were 70% lower. Deficiencies of 50% or more in mitochondrial quality control regulators and selected mitochondrial fission and fusion markers were observed in the SQ fat of MUO monkeys despite comparable mitochondrial content. Conclusions: A novel and translatable spontaneously obese animal model of MHO and MUO, occurring independently of dietary factors, was characterized. Differences in mitochondrial quality and inflammatory cell populations of subcutaneous fat may underpin divergent metabolic health. © 2017 The Obesity Society.


Murphy R.A.,U.S. National Institute on Aging | Register T.C.,Sticht Center on Aging | Shively C.A.,Section on Comparative Medicine Pathology | Carr J.J.,Section on Radiologic science | And 21 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2014

Background. Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics. Methods. VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4-13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics. Results .Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36-2.80; Health ABC) and 1.88 (1.31-2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35-2.28; Health ABC) and 1.56 (1.15-2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12-2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21-2.07), and AGES-Reykjavik, 1.43 (1.07-1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs. Conclusion. VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related. © 2013 The Author.


PubMed | Section on Gerontology and Geriatrics and Vanderbilt University
Type: | Journal: BMC obesity | Year: 2015

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.25 healthy, sedentary, weight-stable men (N=13) and women (N=12) >65years of age, with a BMI range of 18-35kg/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.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).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.ClinicalTrials.gov identifier NCT01049698.


PubMed | Section on Gerontology and Geriatrics, Northwestern University, Stanford University, Pennington Biomedical Research Center and 3 more.
Type: Journal Article | Journal: The journals of gerontology. Series A, Biological sciences and medical sciences | Year: 2016

This subgroup analysis of the Lifestyle Intervention and Independence for Elders trial evaluates the impact of a long-term physical activity (PA) intervention on rates of major mobility disability (MMD) among older adults according to their antihypertensive medication use.Lifestyle Intervention and Independence for Elders study participants were randomized to center-based PA or health education for a median of 2.7 years. Participants were sedentary men and women aged 70-89 years with objectively measured physical limitations. This analysis evaluated rates of MMD and persistent MMD among 1,633 participants, according to antihypertensive medication use. Participants were designated as either (i) an angiotensin-converting enzyme (ACE) inhibitor user (ACEi+), (ii) a user of other antihypertensives not including ACEi (ACEi-), or (iii) nonusers of antihypertensive medications (AHT-). Interactions were explored between antihypertensive use and randomized arm.Interaction terms for MMD (p = .214) and persistent MMD (p = .180) did not reach statistical significance. For MMD, PA displayed marginal effects among ACEi+ (hazard ratio [HR] = 0.76; 95% confidence interval [CI] = 0.57, 1.02) and ACEi- (HR = 0.76; 95% CI = 0.60, 0.97) but not AHT- (HR = 1.19; 95% CI = 0.75, 1.87). For persistent MMD, the effect of PA was greatest among ACEi+ (HR = 0.57; 95% CI = 0.39, 0.84) when compared to ACEi- (HR = 0.76; 95% CI = 0.55, 1.06) or AHT- (HR = 1.18; 95% CI = 0.59, 2.36).The effects of long-term PA on the incidence of MMD and persistent MMD were similar among three subgroups of older adults stratified by their antihypertensive medication use. However, though statistical interactions did not reach significance, several findings may warrant future study in other cohorts given the post hoc nature of this study.


Kalogeropoulos A.P.,Emory University | Georgiopoulou V.V.,Emory University | Murphy R.A.,U.S. National Institute on Aging | Newman A.B.,University of Pittsburgh | And 5 more authors.
JAMA Internal Medicine | Year: 2015

IMPORTANCE: Additional information is needed about the role of dietary sodium on health outcomes in older adults. OBJECTIVE: To examine the association between dietary sodium intake and mortality, incident cardiovascular disease (CVD), and incident heart failure (HF) in older adults. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 10-year follow-up data from 2642 older adults (age range, 71-80 years) participating in a community-based, prospective cohort study (inception between April 1, 1997, and July 31, 1998). EXPOSURES: Dietary sodium intake at baseline was assessed by a food frequency questionnaire. We examined sodium intake as a continuous variable and as a categorical variable at the following levels: less than 1500 mg/d (291 participants [11.0%]), 1500 to 2300 mg/d (779 participants [29.5%]), and greater than 2300 mg/d (1572 participants [59.5%]). MAIN OUTCOMESAND MEASURES: Adjudicated death, incident CVD, and incident HF during 10 follow-up years. Analysis of incident CVD was restricted to 1981 participants without prevalent CVD at baseline. RESULTS: The mean (SD) age of participants was 73.6 (2.9) years, 51.2% were female, 61.7% were of white race, and 38.3% were black. After 10 years, 881 participants had died, 572 had developed CVD, and 398 had developed HF. In adjusted Cox proportional hazards regression models, sodium intake was not associated with mortality (hazard ratio [HR] per 1 g, 1.03; 95% CI, 0.98-1.09; P =.27). Ten-year mortality was nonsignificantly lower in the group receiving 1500 to 2300 mg/d (30.7%) than in the group receiving less than 1500 mg/d (33.8%) and the group receiving greater than 2300 mg/d (35.2%) (P =.07). Sodium intake of greater than 2300 mg/d was associated with nonsignificantly higher mortality in adjusted models (HR vs 1500-2300 mg/d, 1.15; 95% CI, 0.99-1.35; P =.07). Indexing sodium intake for caloric intake and body mass index did not materially affect the results. Adjusted HRs for mortality were 1.20 (95% CI, 0.93-1.54; P =.16) per milligram per kilocalorie and 1.11 (95% CI, 0.96-1.28; P =.17) per 100 mg/kg/m2 of daily sodium intake. In adjusted models accounting for the competing risk for death, sodium intake was not associated with risk for CVD (subHR per 1 g, 1.03; 95% CI, 0.95-1.11; P =.47) or HF (subHR per 1 g, 1.00; 95% CI, 0.92-1.08; P =.92). No consistent interactions with sex, race, or hypertensive status were observed for any outcome. CONCLUSIONS AND RELEVANCE: In older adults, food frequency questionnaire-assessed sodium intake was not associated with 10-year mortality, incident CVD, or incident HF, and consuming greater than 2300 mg/d of sodium was associated with nonsignificantly higher mortality in adjusted models. © 2015 American Medical Association. All rights reserved.

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