Sex differences in the relationships between body composition, fat distribution, and mitochondrial energy metabolism: a pilot study.

BACKGROUND: Adiposity 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. METHODS: Thirty-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. RESULTS: Mitochondrial 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. CONCLUSIONS: These 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.

Physical Fitness but Not Diet Quality Distinguishes Lean and Normal Weight Obese Adults.

BACKGROUND: Individuals with normal weight obesity (NWO) have increased cardiometabolic disease and mortality risk, but factors contributing to NWO development are unknown. OBJECTIVE: The objective of this study was to determine whether diet quality scores and physical fitness levels differed between adults classified as lean, NWO, and overweight-obese. Secondary objectives of the study were to compare clinical biomarkers and food groups and macronutrient intakes between the three groups, and to test for associations between body composition components with diet quality scores and physical fitness levels. DESIGN: This is a secondary data analysis from a cross-sectional study that included metropolitan university and health care system employees. Body composition was measured by dual energy x-ray absorptiometry. Individuals with a body mass index <25 kg/m2 and body fat >23% for men and >30% for women were classified as having NWO. Alternate Healthy Eating Index, Dietary Approaches to Stop Hypertension score, and Mediterranean Diet Score were calculated from Block food frequency questionnaires. Physical fitness was assessed by measuring maximal oxygen uptake (VO2 maximum) during treadmill testing. PARTICIPANTS/SETTING: This study included 693 adults (65% women, mean age 48.9 ± 11.5 years) enrolled between 2007 and 2013 in Atlanta, GA. MAIN OUTCOME MEASURES: The main outcome measures were Alternate Healthy Eating Index, Dietary Approaches to Stop Hypertension, and Mediterranean Diet Score diet quality scores and maximal oxygen uptake. STATISTICAL ANALYSES: Multiple linear regression analyses with post hoc comparisons were used to investigate group differences in fitness, diet quality, and biomarkers. Regression analyses were also used to examine relationships between diet quality scores and fitness with body composition. RESULTS: VO2 maximum was significantly lower in the NWO compared with the lean group (36.2 ± 0.8 mL/min/kg vs 40.2 ± 1.0 mL/min/kg; P < 0.05). Individuals with NWO reported similar diet quality to lean individuals and more favorable Alternate Healthy Eating Index and Dietary Approaches to Stop Hypertension scores than individuals with overweight-obesity (P < 0.05). Diet quality scores and physical fitness levels were inversely associated with percent body fat and visceral adipose tissue (P < 0.05), regardless of weight status. Individuals with NWO exhibited higher fasting blood insulin concentrations, insulin resistance, low-density lipoprotein cholesterol, and triglyceride levels, and significantly lower high-density lipoprotein cholesterol levels than lean individuals (P < 0.05). CONCLUSIONS: Physical fitness was significantly decreased in individuals with NWO compared with lean individuals. Higher diet quality was associated with decreased total and visceral fat but did not distinguish individuals with NWO from lean individuals.

Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.

BACKGROUND: Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. OBJECTIVE: Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. METHODS: Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. RESULTS: eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. CONCLUSION: Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.

Plasma High-Resolution Metabolomics Differentiates Adults with Normal Weight Obesity from Lean Individuals.

OBJECTIVE: This study explored underlying metabolism-related dysfunction by examining metabolomic profiles in adults categorized as lean, as having normal weight obesity (NWO), or as having overweight/obesity. METHODS: Participants (N = 179) had fasting plasma analyzed by liquid chromatography and high-resolution mass spectrometry for high-resolution metabolomics. Body composition was assessed by dual-energy x-ray absorptiometry. NWO was defined as BMI < 25 and body fat > 30% for women and > 23% for men. Differentiating metabolomic features were determined by using linear regression models and likelihood ratio tests with false discovery rate correction. Mummichog was used for pathway and network analyses. RESULTS: A total of 222 metabolites significantly differed between the groups at a false discovery rate of q = 0.2. Linoleic acid, ß-alanine, histidine, and aspartate/asparagine metabolism pathways were significantly enriched (all P < 0.01) by metabolites that were similarly upregulated in the NWO and overweight/obesity groups compared with the lean group. A module analysis linked branched-chain amino acids and amino acid metabolites as elevated in the NWO and overweight/obesity groups compared with the lean group (all P < 0.05). CONCLUSIONS: Metabolomic profiles of individuals with NWO reflected similar metabolic disruption as those of individuals with overweight/obesity. High-resolution metabolomics may help identify people at risk for developing obesity-related disease, despite normal BMI.

Visceral adipose tissue is associated with poor diet quality and higher fasting glucose in adults with cystic fibrosis.

BACKGROUND: Body fat distribution and diet quality influence clinical outcomes in general populations but are understudied in individuals with cystic fibrosis (CF). The aim of this pilot study was to assess body fat distribution and diet quality in relation to fasting glucose and lung function in adults with CF. METHODS: Subjects were 24 adults (ages 18-50) with CF and 25 age-matched controls. The Healthy Eating Index 2015 (HEI-2015) was calculated from 3-day food records and data were adjusted per 1000 kcal. Whole and regional body composition, including visceral adipose tissue (VAT), was assessed by dual energy X-ray absorptiometry. RESULTS: Subjects with CF reported more added sugar intake [26.1 (IQR 18.1) vs. 12.9 (12.5) g/1000 kcal, p < 0.001] and had lower HEI-2015 scores [48.3 (IQR 9.9) vs. 63.9 (27.3), p < 0.001] compared to controls. There were no differences in BMI, total body fat, or lean body mass (LBM) between subjects with CF and controls (p > 0.05 for all), although subjects with CF had higher VAT than control subjects [0.3 (IQR 0.3) vs 0.1 (0.3) kg, p = 0.02]. Among subjects with CF, VAT was positively associated with added sugar intake (p < 0.001) and fasting blood glucose (p = 0.04). Lung function was positively associated with BMI (p = 0.005) and LBM (p = 0.03) but not with adiposity indicators. CONCLUSIONS: These novel data link body fat distribution with diet quality and fasting glucose levels in adults with CF, whereas LBM was associated with lung function. This study highlights the importance of increasing diet quality and assessing body composition and fat distribution in the CF population.