It has been hypothesized that visceral fat releases free fatty acids and adipokines and thereby exposes the liver to fat accumulation. The authors aimed to evaluate current epidemiologic evidence for an association between abdominal fat and liver fat content. Clinical and epidemiologic studies with data on abdominal fat and liver fat content were reviewed. Studies using waist circumference to estimate abdominal fat mass suggested a direct association between abdominal fat and liver fat content. Studies using imaging methods suggested a direct association between intraabdominal fat and liver fat content, but not between subcutaneous abdominal fat and liver fat content. In conclusion, clinical and epidemiologic studies of abdominal fat and liver fat content suggest a direct association between abdominal fat and liver fat content which is probably accounted for by visceral fat. However, results from the included studies do not allow strong conclusions regarding the temporal sequence of events. Future longitudinal studies are recommended to obtain additional information on associations and mechanisms. Both abdominal fat depots and other body compartments of interest should be included to further investigate the association between specific fat depots and liver fat content. Biomarkers may provide insight into underlying mechanisms.
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.
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.
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.
VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related.
Karolinska Institutet, Department of Neurobiology, Care Sciences, and Society, Division of Physiotherapy, Huddinge, and Karolinska University Hospital, SE 141 86 Huddinge and SE 171 76 Solna, Sweden. firstname.lastname@example.org
AIM: To describe age and gender differences in estimated maximum oxygen uptake (VO2max) and participation in organized physical activity in Swedish obese children and adolescents, and compare the results with an age-matched reference group representative of the general population. METHODS: Two hundred and nineteen obese children (102 boys, 117 girls, aged 8-16 years, Body Mass Index (BMI) 24.3-57.0 kg.m-2) performed a submaximal bicycle ergometry test and an interview concerning participation in organized physical activity. RESULTS: The obese children had lower relative VO2max (p
There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity.
Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota.
Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2?±?12.3, HFHS 153.9?±?19.3, BBE 114.4?±?14.3, CLE 82.5?±?13.0, CRE 152.3?±?24.4, ABE 90.6?±?18.0, LGE 95.4?±?10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l?×?min]: chow 14.3?±?1.4, HFHS 31.4?±?3.1, BBE 27.2?±?4.0, CLE 17.7?±?2.2, CRE 32.6?±?6.3, ABE 22.7?±?18.0, LGE 23.9?±?2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice.
Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders.
All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).
BACKGROUND: More and better data are needed to understand the action of physical activity (PA) on insulin resistance and the concomitant relation with body fat in adolescence. OBJECTIVE: We examined the relation between total PA and intensity levels with insulin resistance under special consideration of waist circumference and skinfold thickness. DESIGN: This was a cross-sectional study of 613 adolescents (352 girls, 261 boys) with a mean (+/-SD) age of 15.5 +/- 0.5 y from Sweden and Estonia. Total, low, moderate, and vigorous PA was measured by accelerometry. Body fat estimators included waist circumference and the sum of 5 skinfold thicknesses. Fasting insulin and glucose were measured, and insulin resistance was calculated according to the homeostasis model assessment (HOMA). Linear regression analysis and analysis of covariance were used to determine the association between PA and insulin resistance while considering body fat. All estimates were adjusted for sex, country, pubertal status, and indicators of body fat when applicable. RESULTS: Total, moderate, and vigorous PA were inversely correlated with HOMA. Body fat estimators were positively correlated with HOMA. Significant contrasts in HOMA concentrations were seen when comparing the lower 2 tertiles with the upper tertile of PA indicators. Repeating the analysis with body fat estimators showed significant contrasts in HOMA concentrations when comparing the lower tertiles with the upper tertile. CONCLUSION: In view of an increase in obesity in young people, the results accentuate the role of PA in sustaining metabolic balance in adolescence and the potential benefit of an increase of time spent at higher PA levels for youth with relatively elevated amounts of body fat.
While hypertension still is a major health problem worldwide, some studies have indicated that the blood pressure level has decreased in some populations. This population based cohort study aims at analysing blood pressure changes in a large Norwegian population over a 22 year period.
Data is acquired from three comprehensive health surveys of the HUNT Study conducted from 1984-86 to 2006-08. All citizens of Nord-Trøndelag County, Norway, >20 years were invited: 74,549 individuals participated in 1984-86; 64,523 in 1995-97; and 43,905 in 2006-08.
Both systolic and diastolic blood pressure levels decreased substantially from mid 1980s to mid 2000s, with the most pronounced decrease from 1995-97 to 2006-08 (from 136.0/78.9 to 128.3/70.9 mmHg in women and from 140.1/82.1 to 133.7/76.5 mmHg in men). Although the use of blood pressure lowering medication increased, there was a considerable decrease even in those who reported never use of medication (mean decrease 6.8/7.2 mmHg in women and 6.3/5.3 mmHg in men), and the decrease was most pronounced in the elderly (mean decrease 16.1/12.4 mmHg in women and 14.7/10.4 mmHg in men aged 80+). Mean heart rate, total cholesterol and daily smoking decreased, self-reported hard physical activity increased, while body weight and the prevalence of diabetes increased during the same period.
The BP decrease might seem paradoxically, as body weight and prevalence of diabetes increased during the same period. Salt consumption might have decreased, but no salt data is available. The parallel decrease in mean heart rate might indicate reduction in the white-coat phenomenon, or increased use of beta blockers or calcium channel blockers for other diagnosis than hypertension. Additionally, the data could support the "healthy obese" hypothesis, i.e., that subgroups in the population can sustain obesity without serious health consequences.
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Obesity and SLC2A9 genotype are strong determinants of uric acid levels. However, data on SLC2A9 variants and weight loss induced changes in uric acid levels are missing. We examined whether the changes in uric acid levels two- and ten-years after weight loss induced by bariatric surgery were associated with SLC2A9 single nucleotide polymorphisms (SNPs) in the Swedish Obese Subjects study.
SNPs (N?=?14) identified by genome-wide association studies and exonic SNPs in the SLC2A9 gene locus were genotyped. Cross-sectional associations were tested before (N?=?1806), two (N?=?1664) and ten years (N?=?1201) after bariatric surgery. Changes in uric acid were compared between baseline and Year 2 (N?=?1660) and years 2 and 10 (N?=?1172). A multiple testing corrected threshold of P?=?0.007 was used for statistical significance.
Overall, 11 of the 14 tested SLC2A9 SNPs were significantly associated with cross-sectional uric acid levels at all three time points, with rs13113918 showing the strongest association at each time point (R(2)?=?3.7-5.2%, 3.9?10(-22)=p=7.7?10(-11)). One SNP (rs737267) showed a significant association (R(2)?=?0.60%, P?=?0.002) with change in uric acid levels from baseline to Year 2, as common allele homozygotes (C/C, N?=?957) showed a larger decrease in uric acid (-61.4 ?mol/L) compared to minor allele carriers (A/X: -51.7 ?mol/L, N?=?702). No SNPs were associated with changes in uric acid from years 2 to 10.
SNPs in the SLC2A9 locus contribute significantly to uric acid levels in obese individuals, and the associations persist even after considerable weight loss due to bariatric surgery. However, we found little evidence for an interaction between genotype and weight change on the response of uric acid to bariatric surgery over ten years. Thus, the fluctuations in uric acid levels among the surgery group appear to be driven by the weight losses and gains, independent of SLC2A9 genotypes.
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The presence of obesity-related metabolic disturbances varies widely among obese individuals. Accordingly, a unique subset of obese individuals has been described in the medical literature, which seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as a favorable lipid, inflammation, hormonal, liver enzyme and immune profile. However, recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality. Mechanisms that could explain the favorable metabolic profile of MHO individuals are poorly understood. However, preliminary evidence suggests that differences in visceral fat accumulation, birth weight, adipose cell size and gene expression-encoding markers of adipose cell differentiation may favor the development of the MHO phenotype. Despite the uncertainty regarding the exact degree of protection related to the MHO status, identification of underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping us understand factors that predispose, delay or protect obese individuals from metabolic disturbances. Collectively, a greater understanding of the MHO individual has important implications for therapeutic decision making, the characterization of subjects in research protocols and medical education.
Recent research suggests that tumor necrosis factor-alpha (TNF alpha) may play an important role in obesity-associated insulin resistance and diabetes. We studied the relationship between TNF alpha and the anthropometric and physiological variables associated with insulin resistance and diabetes in an isolated Native Canadian population with very high rates of type 2 diabetes mellitus (DM). A stratified random sample (n = 80) of participants was selected from a population-based survey designed to determine the prevalence of type 2 DM and its associated risk factors. Fasting blood samples for glucose, insulin, triglyceride, leptin, and TNF alpha were collected; a 75-g oral glucose tolerance test was administered, and a second blood sample was drawn after 120 min. Insulin resistance was estimated using the homeostasis assessment (HOMA) model. Systolic and diastolic blood pressure (BP), height, weight, and waist and hip circumferences were determined, and percent body fat was estimated using biological impedance analysis. The relationship between circulating concentrations of TNF alpha and the other variables was assessed using Spearman correlation coefficients, analysis of covariance, and multiple linear regression. The mean TNF alpha concentration was 5.6 pg/mL (SD = 2.18) and ranged from 2.0-12.9 pg/mL, with no difference between men and women (P = 0.67). There were moderate, but statistically significant, correlations between TNF alpha and fasting insulin, HOMA insulin resistance (HOMA IR) waist circumference, fasting triglyceride, and systolic BP (r = 0.23-0.34; all P 0.25). Regression analysis indicated that log HOMA IR and log systolic BP were significant independent contributors to variations in log TNF alpha concentration (model r2 = 0.32). We conclude that in this homogeneous Native Canadian population, circulating TNF alpha concentrations are positively correlated with insulin resistance across a spectrum of glucose tolerance. The data suggest a possible role for TNF alpha in the pathophysiology of insulin resistance.
Subcutaneous fat tissues from an indigenous fat-type breed and an intensively-lean selected breed were studied in juvenile pigs. Combining DIGE with bioinformatics and target analyses of key genes, enzymes or terminal routes, this study identifies metabolic and homeostatic processes, response to organic substances, and acute-phase responses as the main pathways whose proteins were regulated in association with adiposity. Breed-related differences in abundance and activities of malic enzyme and glucose-6-phosphate dehydrogenase NADPH-supplying enzymes suggested up-regulation of the lipogenic pathway to dispose for a greater adiposity. Over-abundance in the lipolytic protein carboxylesterase-1 was revealed in fat-type piglets. A panel of pro- and anti-inflammatory proteins such as serpins, had an altered abundance in the fat-type piglets, suggesting adverse consequences of fat accumulation even in early post-weaning stages. Propensity to low-grade inflammation in fat pigs was reinforced by the up-regulation of genes encoding pro-inflammatory cytokines IL6 and TNF-a in these piglets. Differential abundance in annexin-A5 and pericentrin suggested a positive regulation of cell apoptosis in lean piglets. Our results are relevant in the context of data linking the accretion of body lipids to the physiology and pathology of adipose tissue in models other than rodents for a better control of human health and nutrition.