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Background: The relative proportion of visceral fat (VAT) to subcutaneous fat (SAT) has been described as a major determinant of insulin resistance (IR). Our study sought to evaluate the effect of body fat distribution on glucose metabolism and intrahepatic fat content over time in a multiethnic cohort of obese adolescents., Subjects/methods: We examined markers of glucose metabolism by oral glucose tolerance test, and body fat distribution by abdominal MRI at baseline and after 19.2 ± 11.4 months in a cohort of 151 obese adolescents (88 girls, 63 boys; mean age 13.3 ± 3.4 years; mean BMI z-score 2.15 ± 0.70). Hepatic fat content was assessed by fast-gradient MRI in a subset of 93 subjects. We used the median value of VAT/(VAT + SAT) ratio within each gender at baseline to stratify our sample into high and low ratio groups (median value 0.0972 in girls and 0.118 in boys)., Results: Female subjects tended to remain in their VAT/(VAT + SAT) category over time (change over follow-up P = 0.14 among girls, and P = 0.04 among boys). Baseline VAT/(VAT + SAT) strongly predicted the hepatic fat content, fasting insulin, 2-h glucose, and whole-body insulin sensitivity index at follow-up among girls, but not in boys., Conclusions: The VAT/(VAT + SAT) ratio is a major determinant of impaired glucose metabolism and hepatic fat accumulation over time, and its effects are more pronounced in girls than in boys.

Background/objectives: Fat mass development in infancy contributes to later adiposity, but its relation to ectopic fat depots is unknown. We examined the associations of infant subcutaneous fat with childhood general and organ-specific fat., Subjects/methods: Among 593 children from a population-based prospective cohort study, we obtained total subcutaneous fat mass (as sum of biceps, triceps, suprailiacal, and subscapular skinfolds thickness), central-to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thickness/total subcutaneous fat) at 1.5, 6 and 24 months of age. At 10 years, we assessed BMI, fat mass index (FMI) based on total body fat by dual-energy X-ray absorptiometry, and abdominal subcutaneous, visceral and pericardial fat mass indices, and liver fat fraction by Magnetic Resonance Imaging., Results: A higher central-to-total subcutaneous fat ratio at 1.5 months only and higher total subcutaneous fat at 6 and 24 months were associated with higher BMI, FMI and subcutaneous fat mass index at 10 years. The observed associations were the strongest between total subcutaneous fat at 24 months and these childhood outcomes (difference per 1-SDS increase in total subcutaneous fat: 0.15 SDS (95% Confidence Interval (CI) 0.08, 0.23), 0.17 SDS (95% CI 0.10, 0.24), 0.16 SDS (95% CI 0.08, 0.23) for BMI, FMI and childhood subcutaneous fat mass index, respectively). Infant subcutaneous fat measures at any time point were not associated with visceral and pericardial fat mass indices, and liver fat fraction at 10 years., Conclusions: Our results suggest that infant subcutaneous fat is associated with later childhood abdominal subcutaneous fat and general adiposity, but not with other organ-specific fat depots.

Background/objectives: The phenomenon of adipocyte 'beiging' involves the conversion of non-classic brown adipocytes to brown-like adipose tissue with thermogenic, fat-burning properties, and this phenomenon has been shown in rodents to slow the progression of obesity-associated metabolic diseases. Rodent studies consistently report adipocyte beiging after endurance exercise training, indicating that increased thermogenic capacity in these adipocytes may underpin the improved health benefits of exercise training. The aim of this study was to determine whether prolonged endurance exercise training induces beige adipogenesis in subcutaneous adipose tissues of obese men., Subjects/methods: Molecular markers of beiging were examined in adipocytes obtained from abdominal subcutaneous (AbSC) and gluteofemoral (GF) subcutaneous adipose tissues before and after 6 weeks of endurance exercise training in obese men (n=6, 37.3±2.3 years, 30.1±2.3 kg m -2 )., Results: The mRNAs encoding the brown or beige adipocyte-selective proteins were very lowly expressed in AbSC and GF adipose tissues and exercise training did not alter the mRNA expression of UCP1, CD137, CITED, TBX1, LHX8 and TCF21. Using immunohistochemistry, neither multilocular adipocytes, nor UCP1 or CD137-positive adipocytes were detected in any sample. MicroRNAs known to regulate brown and/or beige adipose development were highly expressed in white adipocytes but endurance exercise training did not impact their expression., Conclusions: The present study reaffirms emerging data in humans demonstrating no evidence of white adipose tissue beiging in response to exercise training, and supports a growing body of work demonstrating divergence of brown/beige adipose location, molecular characterization and physiological function between rodents and humans.

Objectives: We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities., Methods: SAT biopsies were obtained from 19 clinically healthy obese subjects (body mass index (BMI) 34.6±2.7 kg m - 2 ) during a weight loss intervention (0, 5 and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg m -2 ) at baseline. Based on 1-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino-acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography., Results: Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with WL success, and with SAT and VAT glucose uptake. During WL, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 and 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon WL., Conclusions: Higher mitochondrial capacity in SAT predicts good long-term WL success. WL does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it.Data availability:The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.

Background: Emerging data have revealed a negative association between adiposity and muscle quality (MQ). There is a lack of research to examine this interaction among young, healthy individuals, and to evaluate the contribution of adiposity to adaptation after resistance exercise (RE)., Objective: The purpose of this investigation was to examine the influence of subcutaneous adipose tissue (SAT) on muscle function among non-obese individuals before and after RE., Design: Analyses included 634 non-obese (body mass index <30 kg m(-2)) subjects (253 males, 381 females; age=23.3 ± 5.2 years). SAT and muscle mass (magnetic resonance imaging-derived SAT and biceps muscle volume), isometric and dynamic biceps strength, and MQ (strength/muscle volume), were analyzed at baseline and after 12 weeks of unilateral RE., Results: At baseline, SAT was independently associated with lower MQ for males (β=-0.55; P<0.01) and females (β=-0.45; P<0.01), controlling for body mass and age. Adaptation to RE revealed a significant negative association between SAT and changes for strength capacity (β=-0.13; p=0.03) and MQ (β=-0.14; P<0.01) among males. No attenuation was identified among females. Post-intervention SAT remained a negative predictor of MQ for males and females (β=-0.47; P<0.01)., Conclusions: The findings reveal that SAT is a negative predictor of MQ among non-obese, healthy adults, and that after 12 weeks of progressive RE this association was not ameliorated. Data suggest that SAT exerts a weak, negative influence on the adaptive response to strength and MQ among males.