Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol.

BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.

Historical exposure to persistent organic pollutants and risk of incident hypertension.

The aim of this study was to assess the influence of adipose tissue concentrations of a group of persistent organic pollutants (POPs) on the risk of hypertension in an adult cohort of residents of Granada (Southern Spain) over a 10-year follow-up. No chemical was significantly associated with the risk of hypertension in the overall population or when models were stratified by sex or median age. However, we found positive associations between log-transformed POP concentrations and hypertension risk in participants with body mass index (BMI) above the median value of 26.3kg/m(2), which were statistically significant for hexachlorobenzene (HR=1.26, 95% CI=1.03-1.56), ß-hexachlorocyclohexane (HR=1.25, 95% CI=1.03-1.51), and polychlorinated biphenyl congeners -138 (HR=1.32, 95% CI=1.04-1.69) and -153 (HR=1.36, 95% CI=1.00-1.84). Inverse associations were observed in the subgroup with BMI≤26.3kg/m(2), but none was statistically significant. More research and a longer follow-up period are warranted to verify these associations and elucidate the role of obesity as a potential effect modifier. Given the elevated worldwide frequency of POP exposure and hypertension, the public health impact of this relationship may be substantial.

Time-restricted eating and supervised exercise for improving hepatic steatosis and cardiometabolic health in adults with obesity: protocol for the TEMPUS randomised controlled trial.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease is a major public health problem considering its high prevalence and its strong association with extrahepatic diseases. Implementing strategies based on an intermittent fasting approach and supervised exercise may mitigate the risks. This study aims to investigate the effects of a 12-week time-restricted eating (TRE) intervention combined with a supervised exercise intervention, compared with TRE or supervised exercise alone and with a usual-care control group, on hepatic fat (primary outcome) and cardiometabolic health (secondary outcomes) in adults with obesity. METHODS AND ANALYSIS: An anticipated 184 adults with obesity (50% women) will be recruited from Granada (south of Spain) for this parallel-group, randomised controlled trial (TEMPUS). Participants will be randomly designated to usual care, TRE alone, supervised exercise alone or TRE combined with supervised exercise, using a parallel design with a 1:1:1:1 allocation ratio. The TRE and TRE combined with supervised exercise groups will select an 8-hour eating window before the intervention and will maintain it over the intervention. The exercise alone and TRE combined with exercise groups will perform 24 sessions (2 sessions per week+walking intervention) of supervised exercise combining resistance and aerobic high-intensity interval training. All participants will receive nutritional counselling throughout the intervention. The primary outcome is change from baseline to 12 weeks in hepatic fat; secondary outcomes include measures of cardiometabolic health. ETHICS AND DISSEMINATION: This study was approved by Granada Provincial Research Ethics Committee (CEI Granada-0365-N-23). All participants will be asked to provide written informed consent. The findings will be disseminated in scientific journals and at international scientific conferences. TRIAL REGISTRATION NUMBER: NCT05897073.

Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies.

Based on toxicological evidence, children's exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6-12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children's total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS-IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: -8.8%; 95% CI: -16.7, -0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children's exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a "urine concentration bias" that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Sonographic quantification of a hepato-renal index for the assessment of hepatic steatosis in comparison with 3T proton magnetic resonance spectroscopy.

CONTEXT: Nonalcoholic fatty liver disease is the most frequent hepatic disorder in the developed world. Currently, liver biopsy and proton magnetic resonance spectroscopy (H-MRS) are considered the gold standard methods for the quantification of liver fat deposits. OBJECTIVE: To determine whether a Sonographic Hepato-Renal Index (SHRI) calculated using a standard workstation, without a specifically designed software, is an adequate alternative to H-MRS for the quantification of fat liver content and diagnosis of steatosis in the general population. METHODS: A total of 121 volunteers (mean age=46 years, range=21-77 years) were recruited at three medical centers in Granada (Southern Spain) from among individuals attending routine general checkups. All participants were examined by ultrasound and by H-MRS 3T, which served as a reference for the diagnosis of steatosis. The SHRI was calculated as the ratio between the echogenicity of the liver and that of the right renal parenchyma. The validity of the methodology was assessed by receiver operating characteristic curves and correlation tests. RESULTS: The quantitative SHRI showed a strong correlation (Spearman's coefficient=0.89, P<0.001) with the H-MRS 3T. The optimal SHRI cutoff points of 1.21, 1.28, and 2.15 yielded 100% sensitivity for the diagnoses of steatosis greater than 5, 25, and 50%, respectively, with a specificity greater than 70%. CONCLUSION: This study shows that the SHRI is a valid, simple, reliable, and cost-effective screening tool for the identification, assessment, and quantification of hepatic steatosis in the general population.