scholarly journals Subcutaneous fat mass is associated with genetic risk scores related to proinflammatory cytokine signaling and interact with physical activity in middle-aged obese adults

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
James W. Daily ◽  
Hye Jeong Yang ◽  
Meiling Liu ◽  
Min Jung Kim ◽  
Sunmin Park
Keyword(s):  
Physical Activity ◽  
Fat Mass ◽  
Visceral Fat ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Subcutaneous Fat ◽  
Risk Scores ◽  
Obese Adults ◽  
High Physical Activity

Abstract Background and aims Subcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat. Materials and methods Subcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40–65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups. Results Subjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity. Conclusion Obese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat.

Has the time come to integrate genetic risk scores into clinical practice?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F.V Moniz Mendonca ◽  
M.I Mendonca ◽  
A Pereira ◽  
J Monteiro ◽  
J Sousa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Practice ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Risk Scores ◽  
Cumulative Number ◽  
Genetic Risk Scores ◽  
Risk Alleles ◽  
Cad Risk

Abstract Background The risk for Coronary Artery Disease (CAD) is determined by both genetic and environmental factors, as well as by the interaction between them. It is estimated that genetic factors could account for 40% to 55% of the existing variability among the population (inheritability). Therefore, some authors have advised that it is time we integrated genetic risk scores into clinical practice. Aim The aim of this study was to evaluate the magnitude of the association between an additive genetic risk score (aGRS) and CAD based on the cumulative number of risk alleles in these variants, and to estimate whether their use is valuable in clinical practice. Methods A case-control study was performed in a Portuguese population. We enrolled 3120 participants, of whom 1687 were CAD patients and 1433 were normal controls. Controls were paired to cases with respect to gender and age. 33 genetic variants known to be associated with CAD were selected, and an aGRS was calculated for each individual. The aGRS was further subdivided into deciles groups, in order to estimate the CAD risk in each decile, defined by the number of risk alleles. The magnitude of the risk (odds ratio) was calculated for each group by multiple logistic regression using the 5th decile as the reference group (median). In order to evaluate the ability of the aGRS to discriminate susceptibility to CAD, two genetic models were performed, the first with traditional risk factors (TRF) and second with TRF plus aGRS. The AUC of the two ROC curves was calculated. Results A higher prevalence of cases over controls became apparent from the 6th decile of the aGRS, reflecting the higher number of risk alleles present (see figure). The difference in CAD risk was only significant from the 6th decile, increasing gradually until the 10th decile. The odds ratio (OR) for the last decile related to 5th decile (median) was 1.87 (95% CI:1.36–2.56; p<0.0001). The first model yielded an AUC=0.738 (95% CI:0.720–0.755) and the second model was slightly more discriminative for CAD risk (AUC=0.748; 95% CI:0.730–0.765). The DeLong test was significant (p=0.0002). Conclusion Adding an aGRS to the non-genetic risk factors resulted in a modest improvement in the ability to discriminate the risk of CAD. Such improvement, even if statistically significant, does not appear to be of real value in clinical practice yet. We anticipate that with the development of further knowledge about different SNPs and their complex interactions, and with the inclusion of rare genetic variants, genetic risk scores will be better suited for use in a clinical setting. Funding Acknowledgement Type of funding source: None

scholarly journals Carbohydrate and sodium intake and physical activity interact with genetic risk scores of four genetic variants mainly related to lipid metabolism to modulate metabolic syndrome risk in Korean middle-aged adults

2019 ◽  
Vol 122 (8) ◽  
pp. 919-927 ◽  
Author(s):  
Jun-Yu Zhou ◽  
Mi Young Song ◽  
Sunmin Park
Keyword(s):  
Physical Activity ◽  
Metabolic Syndrome ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Risk Scores ◽  
Moderate Activity ◽  
Middle Aged ◽  
Genetic Risk Scores ◽  
Daily Physical Activities ◽  
Middle Aged Adults

AbstractMetabolic syndrome (MetS) risk is influenced by genetic and environmental factors. The present study explored genetic risk scores (GRS) of genetic variants that influence the MetS and the effect of interactions between GRS and nutrient intake on MetS risk. The genetic variants that influence MetS risk were selected by genome-wide association study after adjusting for age, sex, area of residence and BMI in 8840 middle-aged adults. GRS were calculated by summing the risk alleles of the selected SNP and divided into low (0–1), medium (2–3) and high (4–7) risk groups, and the relationships between the MetS and GRS were determined by logistic regression after adjusting covariates involved in MetS risk. We also analysed the interaction between GRS and lifestyles. Four genetic variants (APOA5_rs651821, EFCAB4B_rs4766165, ZNF259_rs2160669 and APOBEC1_rs10845640) were selected because they increased MetS risk after adjusting for covariates. Individuals with medium-GRS and high-GRS alleles had a higher MetS risk by 1·48- and 2·23-fold, respectively, compared with those with low-GRS after adjusting for covariates. The increase in MetS risk was mainly related to serum TAG and HDL-cholesterol concentrations. The GRS had an interaction with carbohydrate (CHO) and Na intakes and daily physical activities for MetS risk. In conclusion, Asian middle-aged adults with high-GRS alleles were at increased MetS risk mainly due to dyslipidaemia. High daily physical activity (≥1 h moderate activity per d) reduced the MetS risk but a low-CHO diet (<65 % of total energy intake) increased the risk in carriers with high-GRS alleles. Low Na intake (<1·6 g Na intake/4 MJ) did not decrease its risk.

scholarly journals Analysis of Activity-Dependent Energy Metabolism in Mice Reveals Regulation of Mitochondrial Fission and Fusion mRNA by Voluntary Physical Exercise in Subcutaneous Fat from Male Marathon Mice (DUhTP)

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2697
Author(s):  
Julia Brenmoehl ◽  
Daniela Ohde ◽  
Christina Walz ◽  
Martina Langhammer ◽  
Julia Schultz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Energy Metabolism ◽  
Fat Mass ◽  
Mitochondrial Fission ◽  
Subcutaneous Fat ◽  
Voluntary Exercise ◽  
Heart Weight ◽  
Mitochondrial Energy Metabolism ◽  
Voluntary Physical Activity

Physical inactivity is considered as one of the main causes of obesity in modern civilizations, and it has been demonstrated that resistance training programs can be used to reduce fat mass. The effects of voluntary exercise on energy metabolism are less clear in adipose tissue. Therefore, the effects of three different voluntary exercise programs on the control of energy metabolism in subcutaneous fat were tested in two different mouse lines. In a cross-over study design, male mice were kept for three or six weeks in the presence or absence of running wheels. For the experiment, mice with increased running capacity (DUhTP) were used and compared to controls (DUC). Body and organ weight, feed intake, and voluntary running wheel activity were recorded. In subcutaneous fat, gene expression of browning markers and mitochondrial energy metabolism were analyzed. Exercise increased heart weight in control mice (p < 0.05) but significantly decreased subcutaneous, epididymal, perinephric, and brown fat mass in both genetic groups (p < 0.05). Gene expression analysis revealed higher expression of browning markers and individual complex subunits present in the electron transport chain in subcutaneous fat of DUhTP mice compared to controls (DUC; p < 0.01), independent of physical activity. While in control mice, voluntary exercise had no effect on markers of mitochondrial fission or fusion, in DUhTP mice, reduced mitochondrial DNA, transcription factor Nrf1, fission- (Dnm1), and fusion-relevant transcripts (Mfn1 and 2) were observed in response to voluntary physical activity (p < 0.05). Our findings indicate that the superior running abilities in DUhTP mice, on one hand, are connected to elevated expression of genetic markers for browning and oxidative phosphorylation in subcutaneous fat. In subcutaneous fat from DUhTP but not in unselected control mice, we further demonstrate reduced expression of genes for mitochondrial fission and fusion in response to voluntary physical activity.

Visceral Fat: Higher Responsiveness of Fat Mass and Gene Expression to Calorie Restriction than Subcutaneous Fat

2003 ◽  
Vol 228 (10) ◽  
pp. 1118-1123 ◽  
Author(s):  
Yin Li ◽  
Hideaki Bujo ◽  
Kazuo Takahashi ◽  
Manabu Shibasaki ◽  
Yanjuan Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Calorie Restriction ◽  
Fat Mass ◽  
Visceral Fat ◽  
Subcutaneous Fat

scholarly journals Polygenic risk modeling with latent trait-related genetic components

2019 ◽  
Author(s):  
Matthew Aguirre ◽  
Yosuke Tanigawa ◽  
Guhan Ram Venkataraman ◽  
Rob Tibshirani ◽  
Trevor Hastie ◽  
...  
Keyword(s):  
Fat Mass ◽  
Genetic Risk ◽  
Complex Traits ◽  
Fat Free Mass ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Genetic Associations ◽  
Polygenic Risk ◽  
Genetic Components ◽  
Mass Component

AbstractPolygenic risk models have led to significant advances in understanding complex diseases and their clinical presentation. While models like polygenic risk scores (PRS) can effectively predict outcomes, they do not generally account for disease subtypes or pathways which underlie within-trait diversity. Here, we introduce a latent factor model of genetic risk based on components from Decomposition of Genetic Associations (DeGAs), which we call the DeGAs polygenic risk score (dPRS). We compute DeGAs using genetic associations for 977 traits in the UK Biobank and find that dPRS performs comparably to standard PRS while offering greater interpretability. We show how to decompose an individual’s genetic risk for a trait across DeGAs components, highlighting specific results for body mass index (BMI), myocardial infarction (heart attack), and gout in 337,151 white British individuals, with replication in a further set of 25,486 non-British white individuals from the Biobank. We find that BMI polygenic risk factorizes into components relating to fat-free mass, fat mass, and overall health indicators like physical activity measures. Most individuals with high dPRS for BMI have strong contributions from both a fat mass component and a fat-free mass component, whereas a few ‘outlier’ individuals have strong contributions from only one of the two components. Overall, our method enables fine-scale interpretation of the drivers of genetic risk for complex traits.

scholarly journals Perinatal, sociodemographic and lifestyle correlates of increased total and visceral fat mass levels in schoolchildren in Greece: the Healthy Growth Study

2016 ◽  
Vol 20 (4) ◽  
pp. 660-670 ◽  
Author(s):  
George Moschonis ◽  
Adriana C Kaliora ◽  
Kalliopi Karatzi ◽  
Aggelos Michaletos ◽  
Christina-Paulina Lambrinou ◽  
...  
Keyword(s):  
Physical Activity ◽  
Fat Mass ◽  
Visceral Fat ◽  
Primary Schools ◽  
Growth Study ◽  
Full Data ◽  
Cross Sectional ◽  
Smoking During Pregnancy ◽  
Healthy Growth ◽  
Mass Level

AbstractObjectiveTo identify possibly independent associations of perinatal, sociodemographic and lifestyle factors with childhood total and visceral body fat.DesignA representative sample of 2655 schoolchildren (9–13 years) participated in the Healthy Growth Study, a cross-sectional epidemiological study.SettingSeventy-seven primary schools in four large regions in Greece.SubjectsA sample of 1228 children having full data on total and visceral fat mass levels, as well as on anthropometric, dietary, physical activity, physical examination, socio-economic and perinatal indices, was examined.ResultsMaternal (OR=3·03 and 1·77) and paternal obesity (OR=1·62 and 1·78), maternal smoking during pregnancy (OR=1·72 and 1·93) and rapid infant weight gain (OR=1·42 and 1·96) were significantly and positively associated with children’s increased total and visceral fat mass levels, respectively. Children’s television watching for >2 h/d (OR=1·40) and maternal pre-pregnancy obesity (OR=2·46) were associated with children’s increased total and visceral fat mass level, respectively. Furthermore, increased children’s physical activity (OR=0·66 and 0·47) were significantly and negatively associated with children’s total and visceral fat mass levels, respectively. Lastly, both father’s age >46 years (OR=0·57) and higher maternal educational level (OR=0·45) were associated with children’s increased total visceral fat mass level.ConclusionsParental sociodemographic characteristics, perinatal indices and pre-adolescent lifestyle behaviours were associated with children’s abnormal levels of total and visceral fat mass. Any future programme for childhood prevention either from the perinatal age or at late childhood should take these indices into consideration.

scholarly journals Impact of Early Infant Growth, Duration of Breastfeeding and Maternal Factors on Total Body Fat Mass and Visceral Fat at 3 and 6 Months of Age

2017 ◽  
Vol 71 (3-4) ◽  
pp. 203-210 ◽  
Author(s):  
Laura M. Breij ◽  
Marieke Abrahamse-Berkeveld ◽  
Dennis Acton ◽  
Emanuella De Lucia Rolfe ◽  
Ken K. Ong ◽  
...  
Keyword(s):  
Fat Mass ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Breastfeeding Duration ◽  
Growth Duration ◽  
Term Infants ◽  
Maternal Characteristics ◽  
Air Displacement Plethysmography ◽  
Total Body ◽  
Duration Of Breastfeeding

Background: Accelerated gain in fat mass in the first months of life is considered to be a risk factor for adult diseases, given the tracking of infancy fat mass into adulthood. Our objective was to assess the influence of early growth, type of feeding and maternal variables on fat mass in early life. Methods: In 300 healthy term infants, we longitudinally measured fat mass percentage (FM%) by air-displacement-plethysmography at 1, 3, and 6 months and abdominal visceral and subcutaneous fat measured by ultrasound at 3 and 6 months. Results: Both gain in FM% and weight-for-length in the first 3 months were positively associated with FM% at 6 months of age and visceral fat at 3 months of age. Gain in FM% and weight-for-length between 3 and 6 months were both positively associated with visceral fat at 6 months. Breastfeeding duration associated positively with subcutaneous fat but not with visceral fat at 3 and 6 months. Maternal characteristics did not associate with FM% or visceral fat at 3 or 6 months. Conclusion: Higher gain in FM% or in weight-for-length in the first postnatal months leads not only to higher FM% but also more to accumulation of visceral fat. Exclusive breastfeeding appears to promote subcutaneous but not visceral fat in the first 6 months.

The 24-Month Changes in Body Fat Mass and Adipokines in Patients Starting Peritoneal Dialysis

2017 ◽  
Vol 37 (3) ◽  
pp. 290-297 ◽  
Author(s):  
Soo Jeong Choi ◽  
Moo Yong Park ◽  
Jin Kuk Kim ◽  
Seung Duk Hwang
Keyword(s):  
Peritoneal Dialysis ◽  
Fat Mass ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Nutrition Status ◽  
Endocrine Organ ◽  
Tnf Α ◽  
Fat Composition ◽  
Serial Change

BackgroundPeritoneal dialysis (PD) is characterized by a gain in fat mass. The fat tissue is a complex endocrine organ that releases various adipokines. In this study, we prospectively examined serial changes of fat composition and adipokines in patients undergoing PD.MethodsBody composition was assessed by computed tomography (CT). Nutrition status and adipokines (leptin, adiponectin, interleukin [IL]-6, and tumor necrosis factor [TNF]-α) were assessed on the 7th day and 6 months, 12 months, and 24 months after the start of PD.ResultsFifty-four patients (28 men), with a mean age of 53.2 ± 13.2 years, were enrolled. Baseline fat mass, especially subcutaneous fat mass, was correlated with baseline leptin (ρ = 0.612), adiponetin (ρ = -0.477), and interleukin-6 (IL-6) (ρ = 0.391). Visceral fat mass was correlated with leptin (ρ = 0.545) and adiponectin (ρ = -0.514). Baseline adiponectin was negatively correlated with baseline leptin (ρ = -0.363). While body weight and leptin increased during the 24 months, serum adiponectin decreased in that period. The changes in visceral and subcutaneous fat mass were greater in the first 12 months and 6 months, respectively. There was no difference in IL-6 and TNF-α. Eight patients died during the follow-up period (mean 47.4 months). Twenty-seven patients continued PD. Increased baseline and serial change of IL-6 level were risk factors for mortality. After adjusting for age, sex, diabetes mellitus (DM), and coronary vascular disease (CVD), the significance of the IL-6 level disappeared.ConclusionsBaseline subcutaneous fat in patients starting PD is correlated with baseline adipokine levels rather than visceral fat. The increase in subcutaneous fat was greatest in the first 6 months. While leptin and adiponectin increased and decreased respectively, IL-6 did not change in the first 24 months.

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