Methods: We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.
Results: PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF.
Conclusion: Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.
METHODS AND FINDINGS: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.
CONCLUSIONS: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.
TRIAL REGISTRATION: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398.
PURPOSE: This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract.
METHODS: By using a combination of 1H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified.
RESULTS: The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified.
CONCLUSION: I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism.
Subjects and Methods: Eighty female adults were recruited and divided into three groups; normal weight (n = 23), overweight (n = 28) and obese (n = 29), according to their BMI. Blood samples were obtained prior to cardiopulmonary exercise testing. Plasma samples were separated by centrifugation and analysed for enzymatic antioxidant activity including catalase, glutathione peroxidase and superoxide dismutase. Non-enzymatic antioxidant activities were assessed using 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging and ferric reducing ability of plasma (FRAP) assays. To evaluate the oxidative stress status of subjects, levels of reactive oxygen species and malondialdehyde, the by-product of lipid peroxidation, were measured. Cardiopulmonary responses were analysed using cardiopulmonary exercise testing (CPET) which involved 15 various parameters such as peak oxygen consumption, metabolic equivalents and respiratory exchange ratio.
Results: The obese group had significantly lower ABTS radical scavenging and FRAP activities than the normal weight group. A higher catalase activity was observed in the obese group than the normal weight group. Spearman's correlation showed an inverse relationship between catalase and peak oxygen consumption, while partial correlation analysis showed inverse correlations between superoxide dismutase and respiratory frequency, ABTS activity and oxygen pulse, and between ABTS activity and cardiac output.
Conclusion: Our results demonstrate a lower cardiovascular fitness and antioxidant capacity in obese women; the higher catalase activity may be a compensatory mechanism. The negative correlations found between these two parameters may indicate the potential effect of antioxidants on the cardiopulmonary system and deserve further analysis in a larger population. Nevertheless, this study provides the basis for future studies to further explore the relationships between redox status and cardiopulmonary responses. This can potentially be used to predict future risk of developing diseases associated with oxidative stress, especially pulmonary and cardiovascular diseases.