Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults

Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129. (AU)

Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults.

Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129.

Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults.

OBJECTIVE: Omega-6 and omega-3 oxylipins are known to play a role in inflammation and cardiometabolic diseases in preclinical models. The associations between plasma levels of omega-6 and omega-3 polyunsaturated fatty acid-derived oxylipins and body composition and cardiometabolic risk factors in young adults were assessed. METHODS: Body composition, brown adipose tissue, traditional serum cardiometabolic risk factors, inflammatory markers, and a panel of 83 oxylipins were analyzed in 133 young adults (age 22.1[SD 2.2] years, 67% women). RESULTS: Plasma levels of four omega-6 oxylipins (15-HeTrE, 5-HETE, 14,15-EpETrE, and the oxidative stress-derived 8,12-iso-iPF2α -VI) correlated positively with adiposity, prevalence of metabolic syndrome, fatty liver index, and homeostatic model assessment of insulin resistance index and lipid parameters. By contrast, the plasma levels of three omega-3 oxylipins (14,15-DiHETE, 17,18-DiHETE, and 19,20-DiHDPA) were negatively correlated with adiposity, prevalence of metabolic syndrome, fatty liver index, homeostatic model assessment of insulin resistance index, and lipid parameters. The panel of seven oxylipins predicted adiposity better than traditional inflammatory markers such as interferon gamma or tumor necrosis factor-alpha. Pathway analyses revealed that individuals with obesity had higher plasma levels of omega-6 and lower plasma levels of omega-3 oxylipins than normal-weight individuals. CONCLUSION: Plasma levels of seven omega-6 and omega-3 oxylipins may have utility as early markers of cardiometabolic risk in young adults.

Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults.

BACKGROUND: Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for inflammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown. METHODS: Cross-sectional study in 100 (65% women) individuals aged 18-25 years from the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study cohort. CVD risk factors, body composition, dietary intake, basal metabolic rate, and cardiorespiratory fitness were assessed by routine methods. Plasma succinate was measured with an enzyme-based assay. Brown adipose tissue (BAT) was evaluated by positron emission tomography, and circulating oxylipins were assessed by targeted metabolomics. Fecal microbiota composition was analyzed in a sub-sample. RESULTS: Individuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+ 42.5%), triglycerides (+ 63.9%), C-reactive protein (+ 124.2%), diastolic blood pressure (+ 5.5%), and pro-inflammatory omega-6 oxylipins than individuals with lower succinate levels. Succinate levels were also higher in metabolically unhealthy individuals than in healthy overweight/obese peers. Succinate levels were not associated with BAT volume or activity or with fecal microbiota composition and diversity. CONCLUSIONS: Plasma succinate levels are linked to a specific pro-inflammatory omega-6 signature pattern and higher VAT levels, and seem to reflect the cardiovascular status of young adults.

Relationship between plasma S-Klotho and cardiometabolic risk in sedentary adults.

This cross-sectional study investigates the relationship between the shed form of the Klotho protein (S-Klotho) in plasma, and cardiometabolic risk in healthy, sedentary adults. The study subjects were 214 healthy, sedentary adults (~64% women). Data were collected during the baseline assessments of two randomized controlled trials: The FIT-AGEING study (n=74 [~50% women] middle-aged adults aged 40-65 years) and the ACTIBATE study (n=140 [~70% women] young adults aged 18-25 years). A sex-specific cardiometabolic risk score was calculated for each subject based on waist circumference, systolic and diastolic blood pressure, and plasma glucose, high-density lipoprotein cholesterol and triglycerides. A significant inverse relationship was detected between S-Klotho and the cardiometabolic risk score of both the middle-aged men and women (ß=-0.658, R2=0.433, P<0.001 and ß=-0.442, R2=0.195, P=0.007) which persisted after adjusting for actual age, energy intake, and VO2max. No significant association was found between S-Klotho and cardiometabolic risk score for the young, healthy adults (P>0.5), nor for the young, healthy men and women when analysed separately (all P>0.1). In conclusion, in healthy, sedentary, middle-aged adults, but not in young, healthy, sedentary adults, higher plasma S-Klotho concentrations are associated with a lower cardiometabolic risk score.

Influence of exposure to pesticides on serum components and enzyme activities of cytotoxicity among intensive agriculture farmers.

Although the effects of acute pesticide poisoning are well known for the pesticides most currently used, hardly any data exist on health effects after long-term low-dose exposures. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The increased utilization of pesticides other than organophosphates makes it even more difficult to find associations. In this study a cohort of 106 intensive agriculture workers were assessed twice during the course of a spraying season for changes in serum biochemistry, namely enzymes reflecting cytotoxicity (AST, ALT, LDH, CK, and amino-oxidase) and other biochemical parameters, such as markers of nephrotoxicity (urea, creatinine) and lipid profile (cholesterol and triglycerides). Several criteria for estimating pesticide exposure were used, the most important one being serum cholinesterase depression greater than 25% from baseline to peak exposure. Our results revealed an association of pesticide exposure with changes in AST (increased activity), LDH, and amino-oxidase (decreased activity) as well as with changes in serum creatinine and phosphorus (lower and higher levels, respectively). These results provide support for a very slight impairment of the liver function, but overall these findings are consistent with no clinically significant hepatotoxicity. Intriguingly, paraoxonase-1 R allele was found to be an independent predictor of higher rates of AST and lower rates of amino-oxidase, so that it may play a supporting role as an individual marker of susceptibility on pesticide-induced health effects. In conclusion, different biomarkers might be used to detect early biochemical effects of pesticides before adverse clinical health effects occur.