Search

Our objective was to interrogate mesenchymal stem cell (MSC) lipid metabolism and gestational exposures beyond maternal body mass that may contribute to child obesity risk. MSCs were cultured from term infants of mothers with obesity (n = 16) or normal weight (n = 15). In MSCs undergoing myogenesis in vitro, we used lipidomics to distinguish phenotypes by unbiased cluster analysis and lipid challenge (24-hour excess fatty acid [24hFA]). We measured MSC AMP-activated protein kinase (AMPK) activity and fatty acid oxidation (FAO), and a composite index of maternal glucose, insulin, triglycerides, free fatty acids, TNF-α, and high-density lipoprotein and total cholesterol in fasting blood from mid and late gestation (~17 and ~27 weeks, respectively). We measured child adiposity at birth (n = 29), 4-6 months (n = 29), and 4-6 years (n = 13). Three MSC clusters were distinguished by triacylglycerol (TAG) stores, with greatest TAGs in Cluster 2. All clusters increased acylcarnitines and TAGs with 24hFA, although Cluster 2 was more pronounced and corresponded to AMPK activation and FAO. Maternal metabolic markers predicted MSC clusters and child adiposity at 4-6 years (both highest in Cluster 3). Our data support the notion that MSC phenotypes are predicted by comprehensive maternal metabolic milieu exposures, independent of maternal BMI, and suggest utility as an at-birth predictor for child adiposity, although validation with larger longitudinal samples is warranted.

BACKGROUND: Sedentary behavior is linked to excess fat mass; however, this association may be inconclusive due to potential measurement errors in self-reported sedentary behavior. OBJECTIVE: To assess the association between changes in sedentary behavior and fat mass in a Cohort of Health Workers (HWCS) from 2004 to 2010. METHODS: A total of 1,285 adults participating in the Cohort of Health Workers were evaluated in 2004 and 2010. Fat mass (kg) was measured by dual X-ray absorptiometry. A self-administered questionnaire was used to estimate the sedentary behavior. Sedentary behavior was also estimated using accelerometry in a sample of 142 health workers. Accelerometry data were used to correct self-reported sedentary behavior using a generalized linear model, which included values for sleeping time, age, sex, sedentary behavior, glucose, and triglycerides. Concordance between both methods was assessed using a kappa and Bland-Altman analysis. Once sedentary behavior was corrected, the values were used to evaluate the association between changes in sedentary behavior and body fat mass using a fixed effect model in the cohort, adjusting for confounders. RESULTS: Self-reported sedentary behavior was 2.8 ± 1.8 and 2.3 ± 1.6 h/day, and body fat mass was 24.9 ± 8.1 and 26.8 ± 8.5 kg in 2004 and 2010, respectively. After applying the correction model, the self-reported sedentary behavior was 7.6 ± 1.2 and 7.5 ± 1.2 h/day in 2004 and 2010, respectively. For every hour increase in corrected sedentary behavior, there was an observed increase of 0.847 (p > 0.001) kg in body fat mass during the 6.8 years in the Cohort of Health Workers from 2004 to 2010. Conversely, non-corrected self-reported sedentary behavior was associated with a non-significant reduction of 0.097 kg (p = 0.228) for every hour of sedentary behavior. CONCLUSIONS: Increased sedentary behavior was associated with increased body fat mass when corrected self-reported sedentary behavior was used. Implementing public health strategies to reduce sedentary behavior is imperative.

STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Womens Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause 3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from ACSMS Body Composition Assessment Book and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Trans vaccenic acid (TVA, trans11-18 : 1) and cis9, trans11-CLA (also known as rumenic acid; RA) have received widespread attention as potentially beneficial trans-FA due to their putative health benefits, including anti-diabetic properties. The objective of this study was to determine the effects of beef fat naturally enriched with TVA and RA on parameters related to glucose homoeostasis and associated metabolic markers in diet-induced obese (DIO) mice. Thirty-six male C57BL/6J mice (8 weeks old) were fed for 19 weeks with either a control low-fat diet (CLF), a control high-fat diet (CHF), or a TVA+RA-enriched high-fat diet (EHF). Compared with CLF, feeding either CHF or EHF resulted in adverse metabolic outcomes associated with high-fat diets, including adiposity, impaired glucose control and hepatic steatosis. However, the EHF diet induced a significantly higher liver weight TAG content and elevated plasma alanine transaminase levels compared with the CHF diet. Collectively, the findings from this study suggest that EHF does not improve glucose tolerance and worsens liver steatosis in DIO mice. However, the adverse effects of EHF on the liver could be in part related to the presence of other trans-FA in the enriched beef fat.

Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22-24 months) compared to saline-injected aged-matched controls. Secretome delivery substantially increased whole-body lean mass and decreased fat mass, corresponding to higher myofiber cross-sectional area and smaller adipocyte size, respectively. Secretome-treated mice also had greater whole-body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome-treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL-6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome-treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction. Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole-body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice.

Background: Recent statistical approaches have allowed consideration of the integrated relationships between sedentary behavior (SB) and physical activity (PA) with different health outcomes. The present paper aimed to systematically review the literature and synthesize evidence about associations between hypothetical reallocations from SB to different PA intensities and cardiovascular risk factors in youth. Methods: A systematic search of 8 databases was performed. Observational studies with a population of children and/or adolescents and based on statistical analysis that investigated the associations between time reallocations from SB to PA and cardiovascular risk factors were included. Results: Twenty-eight studies met the inclusion criteria. Level of evidence (derived from cross-sectional studies) indicated that the reallocation from SB to moderate to vigorous PA was beneficially associated with adiposity, cardiorespiratory fitness, and cardiometabolic biomarkers in youth. Reallocation from SB to light PA was not associated with the analyzed outcomes. Associations derived from longitudinal studies were mostly inconclusive. Conclusion: Cardiovascular risk factors could be improved by increasing moderate to vigorous PA at the expense of time spent in SB in pediatric populations. Prospective studies or studies investigating the effects of reallocating sedentary bouts to PA are needed. [ABSTRACT FROM AUTHOR]

BackgroundSouth Asians are at higher risk for type 2 diabetes (T2D) than many other race/ethnic groups. Ectopic adiposity, specifically hepatic steatosis and visceral fat may partially explain this. Our objective was to derive metabolite risk scores for ectopic adiposity and assess associations with incident T2D in South Asians.MethodsWe examined 550 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40-84 years without known cardiovascular disease or T2D and with metabolomic data. Computed tomography scans at baseline assessed hepatic attenuation and visceral fat area, and fasting serum specimens at baseline and after 5 years assessed T2D. LC-MS-based untargeted metabolomic analysis was performed followed by targeted integration and reporting of known signals. Elastic net regularized linear regression analyses was used to derive risk scores for hepatic steatosis and visceral fat using weighted coefficients. Logistic regression models associated metabolite risk score and incident T2D, adjusting for age, gender, study site, BMI, physical activity, diet quality, energy intake and use of cholesterol-lowering medication.ResultsAverage age of participants was 55 years, 36% women with an average body mass index (BMI) of 25 kg/m2 and 6% prevalence of hepatic steatosis, with 47 cases of incident T2D at 5 years. There were 445 metabolites of known identity. Of these, 313 metabolites were included in the MET-Visc score and 267 in the MET-Liver score. In most fully adjusted models, MET-Liver (OR 2.04 [95% CI 1.38, 3.03]) and MET-Visc (OR 2.80 [1.75, 4.46]) were associated with higher odds of T2D. These associations remained significant after adjustment for measured adiposity.ConclusionsMetabolite risk scores for intrahepatic fat and visceral fat were strongly related to incident T2D independent of measured adiposity. Use of these biomarkers to target risk stratification may help capture pre-clinical metabolic abnormalities.

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P

Loss of lean muscle mass and accumulation of adipose tissue are changes associated with aging. Previous studies have documented various components of body composition as predictors for insulin resistance. The objective of this study was to investigate whether components of body composition-appendicular lean mass (ALM) and/or abdominal fat mass (AFM)-correlate with insulin resistance in older men and women. This was a cross-sectional study of 92 older men and women. Weight was classified according to body mass index (BMI)-normal (BMI 30). All body composition data was determined by dual energy x-ray absorptiometry (DEXA), and insulin resistance was assessed by the homeostatic model assessment of insulin resistance (HOMA-IR). Multivariable regression models with two-way interaction terms were employed to assess whether the associations between components of body composition and log HOMA varied by BMI categories. Adjusted regression showed that log HOMA was significantly associated with AFM (estimate ± standard error: 0.055 ± 0.026) and ALM (0.057 ± 0.029) for the overweight participants (p-values

Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don't. Two explanations have been proposed for this paradoxical finding. One posits that Δ9-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid receptors, stopping their stimulating effects on lipogenesis and adipogenesis. Another explanation is that THC exposure in adolescence, when habitual cannabis use typically starts, produces lasting changes in the developing adipose organ, which impacts adult systemic energy use. Here, we consider these possibilities in the light of a study which showed that daily THC administration in adolescent mice produces an adult metabolic phenotype characterized by reduced fat mass, partial resistance to obesity and dyslipidemia, and impaired thermogenesis and lipolysis. The phenotype, whose development requires activation of CB1 receptors in differentiated adipocytes, is associated with overexpression of myocyte proteins in the adipose organ with unchanged CB1 expression. We propose that adolescent exposure to THC causes lasting adipocyte dysfunction and the consequent emergence of a metabolic state that only superficially resembles healthy leanness. A corollary of this hypothesis, which should be addressed in future studies, is that CB1 receptors and their endocannabinoid ligands may contribute to the maintenance of adipocyte differentiation during adolescence.

Inter-organ communication is a vital process to maintain physiologic homeostasis, and its dysregulation contributes to many human diseases. Given that circulating bioactive factors are stable in serum, occur naturally, and are easily assayed from blood, they present obvious focal molecules for therapeutic intervention and biomarker development. Recently, studies have shown that secreted proteins mediating inter-tissue signaling could be identified by 'brute force' surveys of all genes within RNA-sequencing measures across tissues within a population. Expanding on this intuition, we reasoned that parallel strategies could be used to understand how individual genes mediate signaling across metabolic tissues through correlative analyses of gene variation between individuals. Thus, comparison of quantitative levels of gene expression relationships between organs in a population could aid in understanding cross-organ signaling. Here, we surveyed gene-gene correlation structure across 18 metabolic tissues in 310 human individuals and 7 tissues in 103 diverse strains of mice fed a normal chow or high-fat/high-sucrose (HFHS) diet. Variation of genes such as FGF21, ADIPOQ, GCG, and IL6 showed enrichments which recapitulate experimental observations. Further, similar analyses were applied to explore both within-tissue signaling mechanisms (liver PCSK9) and genes encoding enzymes producing metabolites (adipose PNPLA2), where inter-individual correlation structure aligned with known roles for these critical metabolic pathways. Examination of sex hormone receptor correlations in mice highlighted the difference of tissue-specific variation in relationships with metabolic traits. We refer to this resource as gene-derived correlations across tissues (GD-CAT) where all tools and data are built into a web portal enabling users to perform these analyses without a single line of code (gdcat.org). This resource enables querying of any gene in any tissue to find correlated patterns of genes, cell types, pathways, and network architectures across metabolic organs.

Phenolic compounds show promise in treating obesity and enhancing intestinal health. This systematic review addressed the following question: "What are the effects of polyphenols on intestinal health in preclinical studies with diet-induced obesity?". The review followed PRISMA guidelines and was registered in PROSPERO(CRD42021262445). Studies published until April 2024 were selected from Medline(PubMed), Web of Science, Scopus, Embase, and ScienceDirect using terms related to polyphenols, obesity, and microbiota in rats and mice. Thirty papers meeting PICOS criteria were included. Bias risk was assessed with the SYRCLE tool, yielding scores between 4.5 and 7.0 out of 10. Findings indicated that 22 phenolic compounds improved gut microbiota diversity, reduced the Firmicutes/Bacteroides ratio, and modulated microbiota at various taxonomic levels. They also increased short-chain fatty acids, tight-junction expression, enhanced intestinal morphology, and reduced endotoxemia and inflammatory cytokines. These results suggest phenolic compounds may help treat obesity by modifying the microbiota and improving intestinal health. However, further research is needed to standardize data and facilitate meta-analyses. [ABSTRACT FROM AUTHOR]

Background: Bisphenol S (BPS) is the main substitute for bisphenol A (BPA), a well-known plasticiser and endocrine disruptor. BPS disrupts ovarian function in several species. Moreover, a few studies have reported that the effects of BPS might be modulated by the metabolic status, and none have characterised the granulosa cell (GC) proteome after chronic BPS exposure. Objectives: This study aimed to decipher the mechanisms of action of chronic BPS exposure on the proteome of ewe GCs while considering the interaction between a deliberate contrasted metabolism and reproductive function. Methods: Forty ewes were split into two groups with contrasted diets: restricted (R, n = 20) and well-fed (WF, n = 20). The R and WF ewes were subdivided according to the dose of BPS administered through the diet (0–50 µg/kg/day), forming four groups: R0, R50, WF0 and WF50. After 3-month BPS daily exposure, GCs were recovered during the pre-ovulatory stage and proteins were analysed by nano-liquid chromatography coupled with tandem mass spectrometry. Results: Chronic exposure to BPS affected the GC proteome differently according to the ewe metabolic status. Fifty-nine out of 958 quantified proteins were differentially abundant between groups and are mainly involved in carbohydrate and lipid pathways. Unsupervised hierarchical clustering of differentially abundant proteins (DAPs) identified four clusters of 34, 6, 5 and 14 proteins according to the BPS exposure and diet interaction. Pairwise comparisons between groups also revealed a strong effect of BPS exposure and diet interaction. Functional analysis of DAPs highlighted that BPS upregulated β-glucuronidase (GUSB; p = 0.002), a protein especially able to deconjugate bisphenol glucuronides (BP-g). Moreover, among unexposed ewes, GUSB was detected only in well-fed ewes. Discussion: Conjugation of glucuronides inhibits the oestrogenic activity of bisphenols. Upregulation of GUSB in ewes dosed with BPS would prolong the oestrogenic effects of BPS by deconjugating BPS-g into free BPS. In addition, literature has reported an up-regulation of GUSB in people suffering from obesity. Therefore, people suffering from obesity could be subjected to prolonged and aggravated exposure to BPS. These data highlighted the deleterious effects of BPS and its interaction with metabolic status. [ABSTRACT FROM AUTHOR]

Background: Understanding and finding the correlation between morphometric measurements and horse blood parameters is crucial for predicting equine metabolic issues. Objective: This study aims to analyse morphometric measurements and blood samples in horses with varying adiposity levels. Study design: Cross‐sectional observational. Methods: A total of 50 horses were included in the study and categorized into groups based on their body condition score (BCS) and cresty neck score (CNS). Results: The insulin concentration was significantly higher in overweight horses (p = 0.022). Female horses exhibited higher cortisol concentrations (p = 0.025) and girth circumference at the withers (p = 0.004) compared to males. Lactating mares exhibited higher concentrations of serum total protein (p = 0.012) and globulin (p = 0.003). A positive correlation was observed between BCS and insulin concentrations (r = 0.290, p = 0.041). Negative correlations were found between neck circumference to height at withers and glucose (r = −0.309, p = 0.029), CNS and glucose (r = −0.315, p = 0.026) as well as between crest diameter and cortisol (r = −0.360, p = 0.01). Main limitations: Increasing the sample size and conducting longitudinal studies would enhance the study's validity and reliability. Conclusion: Although insulin, glucose and cortisol concentrations have predictive capabilities based on signs and certain morphometric measurements, their correlations are not always strong. Therefore, this study challenges the notion that all overweight horses are unhealthy, as overweight horses can still have good metabolic health. Conversely, lean horses may also experience metabolic issues. Hence, relying solely on visual cues is insufficient to diagnose the metabolic status of horses. Other factors must also be considered to assess their health status accurately. [ABSTRACT FROM AUTHOR]

Chronic systemic inflammation is a hallmark of obesity. This cross-sectional study aimed to investigate the association between metabolic obesity phenotypes and inflammatory markers in Korean adults (N = 21,112; mean age: 50.9 ± 16.6). Metabolic obesity phenotypes were categorized into metabolically healthy non-obesity (MHNO), metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO) based on body mass index and the presence of any metabolic abnormalities. High-sensitivity C-reactive protein (hs-CRP) levels were measured. Multiple linear regression was used to determine the association between obesity phenotypes and hs-CRP levels. In the male sample, compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 22.3% (95% confidence interval; CI: 14.7–30.3%), 15.8% (95% CI: 2.6–30.7%), and 12.5% (95% CI: 3.0–22.9%) increase in the hs-CRP levels, respectively. The association between metabolic obesity types and hs-CRP levels was stronger among the female sample; compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 30.2% (95% CI: 22.8–38.2%), 16.0% (95% CI: 6.5–26.4%), and 22.8% (95% CI: 13.6–32.8%) increase in the hs-CRP levels, respectively. Our findings indicate a varying profile of systemic inflammation across different metabolic obesity phenotypes. [ABSTRACT FROM AUTHOR]

Background: Little is known about the cardiorespiratory fitness (CRF)‐cardiometabolic risk relationship in Latin American pediatric populations across different age/sex groups, especially when considering the potential effects of adiposity on the association. We evaluated cross‐sectional associations between VO2max and cardiometabolic risk variables (CMRV), and verified whether the associations were independent of adiposity markers in school‐aged children and adolescents from Cali, Colombia. Methods: The sample consisted of 1206 children aged 5–17 years. CMRV were fasting glucose, HDL and LDL cholesterol, triglycerides, systolic, and diastolic pressure. Logistic regressions were conducted for associations of age/sex‐specific tertiles of VO2max with age/sex‐specific highest tertiles of CMRV (except HDL‐C, lowest tertile) and a CMR cluster (> 2 CMRV in extreme tertiles), adjusting for socioeconomic stratum, and adiposity markers (BMI, body fat percentage, and waist circumference). Results: Overweight/obesity ranged from 15% to 18% with no difference by sex. In children aged 5–11 years, high VO2max (highest tertile vs. lowest) was inversely associated with the CMR cluster [Odds ratio (95% confidence interval): 0.18 (0.06–0.47), p < 0.05] independently of adjustment for any adiposity marker in boys but not in girls. In the age group of 12–17 years, there were initially significant VO2max‐ CMR cluster and VO2max‐ CMRV associations but attenuated by adiposity adjustment. In girls, high VO2max was inversely associated with high systolic blood pressure regardless of adjustment for adiposity markers. Conclusion: VO2max is inversely associated with cardiometabolic risk, but adiposity influences the association. The adiposity‐independent association among younger boys requires further research. Interventions to tackle cardiometabolic risk in childhood may primarily focus on reducing excess adiposity, and secondarily on improvement of CRF. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the association of physical activity (PA) levels with all‐cause and cardiovascular disease (CVD) mortality risks stratified by adiposity and age. Methods: Participants (36 703; mean age: 49.1; 57.1% women) were selected from the Korea National Health and Nutrition Examination Survey 2007–2013. A Cox proportional hazards model was used to examine the association between PA and mortality across different adiposity categories and ages. Results: Median follow‐up was 9.22 years; 2393 individuals died, including 538 with CVD. Compared with normal‐weight controls, underweight individuals had increased all‐cause mortality risk (hazard ratio [HR]: 1.60, 95% confidence interval [CI]: 1.33–1.79). The overweight and obese groups demonstrated reduced mortality risks (HRs: 0.75 [95% CI: 0.67–0.84] and 0.59 [95% CI: 0.51–0.67], respectively). Mortality risk based on abdominal obesity had an HR of 1.22 (95% CI: 1.08–1.37). PA protected against mortality risk most in the obese group performing more than 1000 MET‐min/week and was particularly significant among those who were underweight and obese aged 65 and older. Conclusions: Overweight and obese Asian individuals (based on body mass index) had a lower mortality risk than those with normal body mass index, whereas obesity based on waist circumference was associated with increased mortality. PA protected against mortality across various weight categories, especially in individuals aged ≥65. Geriatr Gerontol Int 2024; 24: 1156–1164. [ABSTRACT FROM AUTHOR]

Obesity is a pervasive public health problem that causes debilitating complications across the life course. One opportunity for preventing the onset of obesity is to focus on its social determinants. Socioeconomic status (SES), which includes factors such as income, educational attainment, occupational prestige, and access to resources, is a key determinant of obesity. In this scoping mini-review, we summarized review articles and meta-analyses of the SES-obesity association. From the 1980s to the present, cross-sectional studies have demonstrated a persistent socioeconomic gradient in obesity in which the association is negative in developed countries and positive in developing countries. Longitudinal studies have revealed the bidirectionality of the SES-obesity association; some studies demonstrate that socioeconomic adversity precedes the onset of obesity, while others provide evidence of reverse causality. While earlier studies relied on anthropometric assessments of weight and height to define obesity, the use of modern technologies like dual-energy x-ray absorptiometry and bioelectrical impedance have demonstrated that the socioeconomic gradient in obesity is robust across multiple indicators of body composition, including direct measures of lean and fat mass. More recently, examination of mediators and moderators of the SES-obesity association have highlighted causal pathways and potential intervention targets, with a focus on health behaviors, environmental conditions, psychological factors, and biological processes. We describe current gaps in knowledge and propose opportunities for future innovation to reduce the burden of obesity and related socioeconomic disparities. [ABSTRACT FROM AUTHOR]

Context Obesity is a disease with deleterious effects on the female reproductive tract, including the endometrium. Objective We sought to understand the effects of excess adipose on the benign endometrium. Methods A physiologic in vitro coculture system was developed, consisting of multicellular human endometrial organoids, adipose spheroids, and menstrual cycle hormones. Native human endometrial tissue samples from women with and without obesity were also analyzed. Benign endometrial tissues from premenopausal women ages 33 to 53 undergoing hysterectomy were obtained following written consent at Northwestern University Prentice Women's Hospital, Chicago, Illinois. Gene expression, protein expression, chromatin binding, and expression of DNA damage and oxidative damage markers were measured. Results Under high adiposity conditions, endometrial organoids downregulated endometrial secretory phase genes, suggestive of an altered progesterone response. Progesterone specifically upregulated the metallothionein (MT) gene family in the epithelial cells of endometrial organoids, while high adiposity significantly downregulated the MT genes. Silencing MT genes in endometrial epithelial cells resulted in increased DNA damage, illustrating the protective role of MT s. Native endometrium from women with obesity displayed increased MT expression and oxidative damage in the stroma and not in the epithelium, indicating the cell-specific impact of obesity on MT genes. Conclusion Taken together, the in vitro and in vivo systems used here revealed that high adiposity or obesity can alter MT expression by decreasing progesterone response in the epithelial cells and increasing oxidative stress in the stroma. [ABSTRACT FROM AUTHOR]

Background: Maternal preconception overweight status has been reported to be associated with an increased risk of overweight offspring. However, there are no published population-based studies on the association between maternal preconception weight and offspring body fat measured by dual-energy X-ray absorptiometry (DXA). The present population-based retrospective cohort study aimed to examine the association between maternal weight at conception and offspring body fat measured by DXA. Methods: The source population consisted of 5th-grade students (1244 students aged 11 years) registered at 8 municipal elementary schools in Kitakata, Fukuroi, Hamamatsu, and Himeji in Japan. The present analyses included 964 participants who provided complete information. Maternal body mass index (BMI) at conception was calculated using records in the Mother and Child Health Handbook (MCHH). Offspring body fat at age 11 years was measured with the same QDR-4500A DXA instrument in a mobile test room that was brought to each school. With regard to the prediction of excess fat in offspring, the area under the curve (AUC) calculated with receiver operating characteristic curve analysis was used to quantify the diagnostic accuracy of maternal BMI at conception. Results: Adjusted odds ratios for excess body fat in offspring of the overweight mother group (odds ratios, 4.93 to 15.32) were significantly higher than those in the non-overweight mother group. For the prediction of excess offspring fat, AUCs and 95% confidence intervals for maternal BMI at conception were greater than 0.5. Conclusion: Maternal overweight status at conception might be a risk factor for excess body fat in offspring. Maternal BMI values calculated using MCHH data have the potential to distinguish between the presence and absence of excess fat in the next generation. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy (HDP) are a prevalent complication during pregnancy with significant implications for maternal and perinatal health globally. Maternal obesity is a known risk factor for HDP. This review sought to identify adiposity indicators in early pregnancy that are linked to the development of HDP. Methods: We conducted a systematic search of the PubMed, Science Citation Index (Web of Science), and Embase databases. Screening and quality evaluation of studies was conducted independently by two reviewers. Both random effects meta-analysis and narrative synthesis were performed. Results: Thirty-one studies were included with a pooled sample of 81,311 women. The meta-analysis showed that the odds of HDP were significantly increased by higher pregnancy measures of adiposity (pre-pregnancy body mass index (OR = 2.14, 95%CI: 1.67–2.75), visceral adipose tissue (OR = 1.79, 95%CI: 1.01–3.16), subcutaneous adiposity thickness (OR = 1.67, 95%CI: 1.36–2.05), waist circumference (OR = 2.20, 95%CI: 1.37–3.54), waist to-hip ratio (OR = 3.08, 95% CI: 1.38–6.87), weight gain (OR = 1.69, 95%CI: 1.42–2.02) and percentage body fat (OR = 1.71, 95%CI: 1.16–2.53)). Epicardial fat thickness was significantly associated with HDP, although limited data were available. Conclusions: The results of our study highlight the importance of investigating the predictive value of adiposity measures in identifying the risk of HDP to tailor care towards women at the highest risk. [ABSTRACT FROM AUTHOR]

Background: Understanding the causal relations between dietary habits and stroke is crucial for prioritizing public health interventions and developing effective health strategies. This study utilized Mendelian randomization (MR) analysis to examine the causal associations between 20 dietary habits and various stroke subtypes, aiming to identify potential mediators and evaluate the proportions of mediation. Methods: A two-sample MR analysis was conducted to examine the causal relationships between dietary habits and stroke incidence. Mediation analysis, two-step MR (TSMR), and multivariable MR (MVMR) were employed to identify potential mediators. Genetic data pertaining to dietary habits and stroke were obtained from extensive genome-wide association study (GWAS) consortia. The inverse variance-weighted (IVW) method served as the primary analytical approach, with the additional scrutiny of significant correlations conducted through the Egger regression, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and weighted median techniques. Results: Our analyses indicated that genetically predicted intakes of dried fruits, cheese, cereal, oily fish, and hot drink temperatures were protective against stroke, whereas higher intakes of lamb/mutton, poultry, and added salt significantly elevated stroke risk. Specifically, dried fruit consumption demonstrated a protective effect against total stroke (β = −0.009, p = 0.013), ischemic stroke (β = −0.475, p = 0.003), and small-vessel ischemic stroke (β = −0.682, p = 0.033) through reductions in BMI levels, accounting for mediated proportions of 3.2%, 17.1%, and 8.5%, respectively. Furthermore, cheese intake provided a protective effect against ischemic stroke (β = −0.275, p = 0.003) by decreasing BMI and increasing HDL-C levels, with mediated proportions of 30.5% and 6.5%. Together, BMI and HDL-C accounted for 34.9% of the beneficial effect of cheese intake on reducing the risk of ischemic stroke. In contrast, an increased salt intake exhibited a positive association with large-artery ischemic stroke (β = 0.432, p = 0.033) through BMI elevation, with a mediated proportion of 10.9%. Conclusions: Our findings provide compelling evidence supporting causal relationships between dietary habits and stroke subtypes, while identifying mediators and evaluating the proportions of mediation. Adhering to a low-calorie, nutrient-dense diet enriched with dried fruits, cheese, and cereal, along with reduced salt and poultry consumption, could potentially mitigate stroke risk. [ABSTRACT FROM AUTHOR]

Background: Health literacy is a core public health issue in relation to children and adolescents associated with multiple health behaviours and health outcomes. The aim of the study is to test the direct associations between health literacy, physical activity behaviour, health outcomes of body composition and cardiorespiratory fitness among Slovak adolescents and possible indirect effect of health literacy on health outcomes of body composition and cardiorespiratory fitness mediated by adolescents' physical activity behaviour. Methods: Data from the Slovak Health Behaviour in School-aged Children (HBSC) study conducted in 2022 were used. For the purposes of this study, a subsample of the adolescents (n = 508; mean age = 14.50; SD = 0.82; 54.3% boys) which provided HBSC questionnaire data on health literacy, moderate-to-vigorous physical activity and vigorous physical activity and participated in body composition (InBody 230) and cardiorespiratory fitness (20-m shuttle run test) measurements. Data were analysed using linear regression analysis. Results: The findings showed that higher health literacy of the adolescents was directly associated with higher frequency of physical activity represented by moderate-to-vigorous physical activity and vigorous physical activity and only with the visceral fat area in the crude model. Furthermore, there was an indirect effect of health literacy on cardiorespiratory fitness and most of the body composition variables (except the Body Mass Index) which was mediated by physical activity of the respondents. Conclusions: Health literacy is indirectly associated to body composition and cardiorespiratory fitness through higher frequency of physical activity. It seems that health literacy as cognitive and social competencies need behavioural components to be involved in the proposed causal pathway between health literacy and health outcomes. Our findings may contribute to the process of creating a framework for future health literacy interventions in adolescents. [ABSTRACT FROM AUTHOR]

Summary A footnote in Adolphe Quetelet's classic 1835 Treatise on Man described his algebraic analysis of how body weight (W$$ W $$) varies with height (H$$ H $$) in adult males and females. Using data on 12 short and 12 tall subjects of each sex, Quetelet established the rule that W$$ W $$ is approximately proportional (∝$$ \propto $$) to H2 in adults; that is, W∝H2$$ W\propto {H}^2 $$ when W≈αH2$$ W\approx \alpha {H}^2 $$ for some constant α$$ \alpha $$. Quetelet's Rule (W∝H2$$ W\propto {H}^2 $$), transformed and renamed in the twentieth century to body mass index (BMI=W/H2$$ \mathrm{BMI}=W/{H}^2 $$), is now a globally applied phenotypic descriptor of adiposity at the individual and population level. The journey from footnote to ubiquitous adiposity measure traveled through hundreds of scientific reports and many more lay publications. The recent introduction of highly effective pharmacologic weight loss treatments has heightened scrutiny of BMI's origins and appropriateness as a gateway marker for diagnosing and monitoring people with obesity. This contemporary context prompted the current report that delves into the biological and mathematical paradigms that underlie the simple index BMI=W/H2$$ \mathrm{BMI}=W/{H}^2 $$. Students and practitioners can improve or gain new insights into their understanding of BMI's historical origins and quantitative underpinning from the provided overview, facilitating informed use of BMI and related indices in research and clinical settings. [ABSTRACT FROM AUTHOR]

Background: Neighborhood poverty is associated with adiposity in women, though longitudinal designs, annually collected residential histories, objectively collected anthropometric measures, and geographically diverse samples of midlife women remain limited. Objective: To investigate whether longitudinal exposure to neighborhood concentrated poverty is associated with differences in body mass index (BMI) and waist circumference (WC) among 2,328 midlife women (age 42–52 years at baseline) from 6 U.S. cities enrolled in the Study of Women's Health Across the Nation (SWAN) from 1996 to 2007. Methods: Residential addresses and adiposity measures were collected at approximately annual intervals from the baseline visit through a 10-year follow-up. We used census poverty data and local spatial statistics to identify hot-spots of high concentrated poverty areas and cold-spots of low concentrated poverty located within each SWAN site region, and used linear mixed-effect models to estimate percentage differences (95% confidence interval [CI]) in average BMI and WC levels between neighborhood concentrated poverty categories. Results: After adjusting for individual-level sociodemographics, health-related factors, and residential mobility, compared to residents of moderate concentrated poverty communities, women living in site-specific hot-spots of high concentrated poverty had 1.5% higher (95% CI: 0.6, 2.3) BMI and 1.3% higher (95% CI: 0.5, 2.0) WC levels, whereas women living in cold-spots of low concentrated poverty had 0.7% lower (95% CI: −1.2, −0.1) BMI and 0.3% lower (95% CI: −0.8, 0.2) WC. Site-stratified results remained in largely similar directions to overall estimates, despite wide CIs and small sample sizes. Conclusions: Longitudinal exposure to neighborhood concentrated poverty is associated with slightly higher BMI and WC among women across midlife. [ABSTRACT FROM AUTHOR]

• Better diet quality had a direct (beneficial) effect on pain. • Higher consumption of core foods was related to less pain in women, but not men. • Adiposity did not mediate the relationship between diet quality and pain. • Strategies for pain management should consider diet quality. Dietary intake has been associated with pain and physical function, but it is unclear if these relationships are mediated by adiposity. Data were derived from the Whyalla Intergenerational Study of Health (n = 654, 57% women). Structural equation modelling tested the hypotheses that adiposity (body mass index (BMI), waist circumference (WC), or body fat (BF, dual energy x-ray absorptiometry)) would mediate the relationship between diet quality (Dietary Guideline Index (DGI) total, core, or non-core scores) and pain (Short Form-36 bodily pain scale (SF36-BPS)), or physical function (grip-strength), overall, and by gender. Adiposity did not mediate a relationship between DGI scores and pain. Direct effects were observed between DGI total scores and SF36-BPS accounting for BMI (β = 0.170, 95% CI 0.002, 0.339), and between DGI core food scores and SF36-BPS (BMI, β = 0.278, 95% CI 0.070, 0.486; WC, β = 0.266, 95% CI 0.058, 0.474; BF, β = 0.266, 95% CI 0.060, 0.473). In women, direct effects existed between DGI scores and SF36-BPS (DGI total scores, BMI, β = 0.388, 95% CI 0.162, 0.613; WC, β = 0.372, 95% CI 0.146, 0.598; BF, β = 0.382, 95% CI 0.158, 0.605, and DGI core scores, BMI, β = 0.482, 95% CI 0.208, 0.757; WC, β = 0.472, 95% CI 0.197, 0.747; BF, β = 0.467, 95% CI 0.195, 0.739), and DGI total scores and grip-strength (BMI, β = 0.075, 95% CI 0.008, 0.142; WC, β = 0.076, 95% CI 0.009, 0.143; BF, β = 0.079, 95% CI 0.011, 0.146). Better diet quality is associated with lower bodily pain, irrespective of adiposity. Findings highlight the potential role of diet quality in pain management and function, particularly in women. A cross-sectional study of 654 Australian adults (57% women) from the WISH found better diet quality, particularly the intake of core foods, assessed via the DGI, was associated with lower body pain. These findings were most pronounced in women. Mediation analyses did not show any influence of adiposity in this relationship. Abbreviations: BMI, body mass index; DGI, Dietary Guideline Index; WISH, Whyalla Intergenerational Study of Health. [Display omitted] [ABSTRACT FROM AUTHOR]

Increased cardiometabolic risk among children is increasingly becoming a concern, with evidence indicating that obesity, diet, and serum 25-hydroxyvitamin D (25(OH)D) are associated with cardiometabolic risk. However, such studies among Malaysian children are scarce. Thus, this study explores the associations between adiposity, dietary quality, and 25(OH)D, with cardiometabolic risk factors among Malaysian children aged 4–12 years. Data of 479 children (mean age: 8.2 ± 2.3 years old, 52% females) from the South East Asian Nutrition Surveys (SEANUTS II) Malaysia, were included in this analysis. Adiposity (percentage of body fat) was assessed with bioelectrical impedance technique. Dietary quality was assessed using 24 h dietary recall and calculated as mean adequacy ratio. Vitamin D was assessed based on serum 25-hydroxyvitamin D (25(OH)D). Measurements of cardiometabolic risk factors included waist circumference (WC), mean arterial pressure (MAP), fasting blood glucose (FBG), high-density lipoprotein (HDL), triglyceride, and high-sensitivity C-reactive protein, and cardiometabolic risk cluster score (siMS) was calculated. Overall, higher adiposity was positively associated with all cardiometabolic risk factors (WC, ß = 0.907; 95% CI = 0.865, 0.948; MAP, ß = 0.225; 95% CI = 0.158, 0.292; HDL, ß = −0.011; 95% CI = −0.014, −0.009; Triglyceride, ß = 0.012; 95% CI = 0.009, 0.016; FBG, ß = 0.006; 95% CI = 0.002, 0.011) and siMS score (ß = 0.033; 95% CI = 0.029, 0.037). Serum 25(OH)D was inversely associated with siMS score (ß = −0.002; 95% CI = −0.004, −0.000008) and positively associated with HDL (ß = 0.002; 95% CI = 0.0001, 0.003). Our findings suggest that adiposity is a key determinant of adverse cardiometabolic risk factors in children, while serum 25(OH)D may be associated with overall cardiometabolic health. Interventions to reduce obesity are needed to mitigate the deleterious consequences of cardiometabolic dysregulation in children. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Less than 50% of patients treated for hypertension reach a target office systolic blood pressure (SBP). We aimed to evaluate the role of adiposity on antihypertensive drug responses in newly diagnosed hypertensive patients.Estimated glomerular filtration rates, body mass index (BMI), skinfold thickness (SFT), body surface areas and waist circumferences of 150 hypertensive patients naïve to treatment were measured. Treatment protocols were started as combination of angiotensin converting enzyme inhibitor (ACE‐I) plus calcium channel blocker (CCB), angiotensin receptor blocker plus CCB or ACE‐I plus diuretic. Pre‐treatment and change in blood pressure (ΔBP) after 4 weeks treatment were determined. Multiple linear regression analysis was used to find independent predictors of Δblood pressure changes, and multivariable binary logistic regression analysis to find independent predictors of target SBP < 140 mmHg at 4 weeks.A total of 104 patients reached the target systolic pressure of <140 mmHg at 4 weeks. Triceps, mid‐abdomen and subscapular SFT were significantly thicker in the uncontrolled blood pressure group (P = .011, P = .006 and P = .016, respectively). Pretreatment SBP (r = 0.644), pretreatment diastolic blood pressure (DBP) (r = 0.188), subscapular SFT (r = −0.318), suprailiac SFT (r = −0.211) and ΔDBP (r = 0.433) were correlated with ΔSBP in correlation analysis. Pretreatment SBP (β = 0.644, 95% CI = 0.697–0.993, P < .001), subscapular SFT (β = −0.253, 95% CI = −0.886–−0.329, P < .001), pretreatment DBP (β = −0.380, 95% CI = −0.1001– −0.453, P = .001) and ΔDBP (β = 0.401, 95% CI = 0.377–0.796, P < .001) were independent predictors of ΔSBP in multivariable linear regression analysis. Subscapular SFT was an independent predictor of target SBP < 140 mmHg in multivariable logistic regression analysis (OR = 0.895, 95% CI = 0.832–0.963, P = .003).Subscapular SFT may be a valuable marker for prediction of response to antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. Objective: To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. Method: From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. Result: Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). Conclusion: Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity. [ABSTRACT FROM AUTHOR]

Background/Objectives: To assess associations between dietary fibre intake, adiposity, and odds of metabolic syndrome in Pacific and New Zealand European women. Methods: Pacific (n = 126) and New Zealand European (NZ European; n = 161) women (18–45 years) were recruited based on normal (18–24.9 kg/m2) and obese (≥30 kg/m2) BMIs. Body fat percentage (BF%), measured using whole body DXA, was subsequently used to stratify participants into low (<35%) or high (≥35%) BF% groups. Habitual dietary intake was calculated using the National Cancer Institute (NCI) method, involving a five-day food record and semi-quantitative food frequency questionnaire. Fasting blood was analysed for glucose and lipid profile. Metabolic syndrome was assessed with a harmonized definition. Results: NZ European women in both the low- and high-BF% groups were older, less socioeconomically deprived, and consumed more dietary fibre (low-BF%: median 23.7 g/day [25–75-percentile, 20.1, 29.9]; high-BF%: 20.9 [19.4, 24.9]) than Pacific women (18.8 [15.6, 22.1]; and 17.8 [15.0, 20.8]; both p < 0.001). The main source of fibre was discretionary fast foods for Pacific women and whole grain breads and cereals for NZ European women. A regression analysis controlling for age, socioeconomic deprivation, ethnicity, energy intake, protein, fat, and total carbohydrate intake showed an inverse association between higher fibre intake and BF% (β= −0.47, 95% CI = −0.62, −0.31, p < 0.001), and odds of metabolic syndrome (OR = 0.91, 95% CI = 0.84, 0.98, p = 0.010) among both Pacific and NZ European women (results shown for both groups combined). Conclusions: Low dietary fibre intake was associated with increased metabolic disease risk. Pacific women had lower fibre intakes than NZ European women. [ABSTRACT FROM AUTHOR]

Background/Objectives: The phyla Firmicutes and Bacteroidetes are the main constituents of the gut microbiota. An imbalance in the gut microbiota is a sign of dysbiosis, and the Firmicutes-to-Bacteroidetes ratio has been proposed to be a marker of it, especially in the context of obesity. Since Croatia is the country with one of the highest obesity rates in Europe, a pilot observational study was conducted. The aim of the study was to investigate the validity of this potential biomarker in a methodological study using sample processing, DNA sequence analysis and characterization of recruited participants, including various health factors. Methods: A study involving Croatian population was conducted. Participants age, body weight, gender, health history and lifestyle factors were recorded. Gut microbiota composition was analyzed using 16S rRNA sequencing. The F/B ratio was calculated and evaluated in the context of health factors. Statistical analysis was performed to detect the possible association of F/B ratio and excess body weight (kg) and possible impact of certain lifestyle factors. Results: No association between the F/B ratio and excess body weight (kg) was found. Excess body weight was significantly associated with higher age, male gender, and history of appendectomy. No significant health predictors of the F/B ratio were found, but weight gain was positively associated with a higher average F/B ratio. Conclusions: Although this study could not confirm the predictive value of the F/B ratio or any other phyla-related biomarker for excess body weight in the study population, it demonstrated interesting insights into the obesity-associated gut microbiota. [ABSTRACT FROM AUTHOR]

As adiposity increases in youth, so does the prevalence of cardiometabolic risk factors (CMRFs). The etiology of adiposity-based chronic disease and CMRFs includes ethnoracial disparities that are rarely considered in current treatment approaches. Precision interventions require further characterization of these disparities among high-risk youth. The objective of this study was to characterize differences in CMRF among African American (AA) and Hispanic (H) adolescents with varying levels of adiposity. A cross-sectional analysis of 2284 adolescents aged 12–17 was conducted using 3-year clinical data from Lifedoc Health. CMRF prevalence were compared using χ2, with logistic regression models (LRM) applied to explore the relationships between exposures (age, sex, ethnoracial group, adiposity) and CMRF outcomes. Prevalence of CMRF rose with increasing adiposity, which was the strongest determinant of risk overall. However, individual risk profiles differed between the two groups, with H having higher prevalence of metabolic syndrome (MetS), higher triglycerides and liver enzymes, and low high-density lipoprotein cholesterol (HDL-c). Meanwhile, AA had higher prevalence of elevated blood pressure (BP) in the overweight category, prediabetes in overweight to severe obesity, and type 2 diabetes in obesity. LRM showed 3.0-fold greater chance of impaired glucose metabolism in AA than H, who were 1.7, 5.9, and 8.3 times more likely to have low HDL-c, high liver enzymes, and high triglycerides, respectively. Overweight/obesity prevalence was very high among AA and H adolescents. Excess adiposity was associated with an increased prevalence of CMRF, with individual risk factors differing between groups as adiposity increased. Research within routine clinical settings is required to better characterize these discrepancies and ameliorate their adverse impact on health in the transition to adulthood. [ABSTRACT FROM AUTHOR]

Background: Adiposity shows opposing associations with mortality within COVID-19 versus non-COVID-19 respiratory conditions. We assessed the likely causality of adiposity for mortality among intensive care patients with COVID-19 versus non-COVID-19 by examining the consistency of associations across temporal and geographical contexts where biases vary. Methods: We used data from 297 intensive care units (ICUs) in England, Wales, and Northern Ireland (Intensive Care National Audit and Research Centre Case Mix Programme). We examined associations of body mass index (BMI) with 30-day mortality, overall and by date and region of ICU admission, among patients admitted with COVID-19 (N = 34,701; February 2020–August 2021) and non-COVID-19 respiratory conditions (N = 25,205; February 2018–August 2019). Results: Compared with non-COVID-19 patients, COVID-19 patients were younger, less often of a white ethnic group, and more often with extreme obesity. COVID-19 patients had fewer comorbidities but higher mortality. Socio-demographic and comorbidity factors and their associations with BMI and mortality varied more by date than region of ICU admission. Among COVID-19 patients, higher BMI was associated with excess mortality (hazard ratio (HR) per standard deviation (SD) = 1.05; 95% CI = 1.03–1.07). This was evident only for extreme obesity and only during February–April 2020 (HR = 1.52, 95% CI = 1.30–1.77 vs. recommended weight); this weakened thereafter. Among non-COVID-19 patients, higher BMI was associated with lower mortality (HR per SD = 0.83; 95% CI = 0.81–0.86), seen across all overweight/obesity groups and across dates and regions, albeit with a magnitude that varied over time. Conclusions: Obesity is associated with higher mortality among COVID-19 patients, but lower mortality among non-COVID-19 respiratory patients. These associations appear vulnerable to confounding/selection bias in both patient groups, questioning the existence or stability of causal effects. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular adenoma (HCA) is a rare benign neoplasm, seldom ascribed as the cause of endocrine and metabolic derangement. We herein report a case of primary amenorrhea, growth arrest and metabolic syndrome. En bloc resection of the tumor normalized all the disturbances. Case presentation: A 16-year-old girl complained of primary amenorrhea and growth arrest for the past 2 years. Her height and weight were at the 3rd percentile, whereas waist circumference was at the 90th percentile for chronological age. She was hypertensive on admission. Plasma cholesterol, triglyceride and uric acid were elevated. Evaluation of GH/IGF-1 axis showed extremely low IGF-1 concentration, which was unresponsive to hGH stimulation. Computer tomography identified a huge liver mass (18.2 cm×13.7 cm×21 cm). The patient underwent an uneventful open right hepatic lobectomy. The tumor was en bloc resected. Immunohistochemistry indicated an unclassified HCA, which was confirmed by genetic screening. IGF-1 concentration, blood pressure, lipid profile and ovarian function were all normalized after surgery, and the girl had reduction in waist circumference and gain in height during the follow up. Conclusion: We provide evidence that liver-derived IGF-1 has a direct effect on skeletal and pubertal development, blood pressure, visceral adiposity and dyslipidemia independent of insulin resistance and obesity in the circumstance of undernutrition. Though rare, we propose the need to look into HCA cases for the existence of IGF-1 deficiency and its impact on metabolic derangement. [ABSTRACT FROM AUTHOR]

Aims: The impact of life-course different adiposity indices on diabetes mellitus (DM) is poorly understood. We aimed to do trajectory analysis with repeated measurements of adiposity indices in the development of DM among women across the lifespan. Methods: This study prospectively investigated the 1,681 population of Tehran Lipid and Glucose Study. At baseline, all individuals were free of diabetes. Trajectory analysis was used to identify homogeneous distinct clusters of adiposity indices trajectories and assign individuals to unique clusters. Results: Of the 1681 healthy women, 320 progressed to the DM. Three distinct body mass index (BMI) trajectories and 2 distinct trajectories of other adiposity indices (waist circumstance (WC), conicity index (C-index), and body roundness index (BRI)) were chosen as the best fitting of the latent class growth mixture model. In the adjusted model, total participants [HR (CI 95%): 2.83 (2.05, 3.91); p < 0.001], and menopause [1.35 (1.10, 2.11); p = 0.001] and reproductive-age women [2.93 (1.80, 4.78); p = 0.003] of the high BMI trajectory compared to the ones in the low trajectory of BMI were more likely to develop DM. The high BRI in menopause had a significantly higher risk of DM compared to the low trajectory. In menopause (1.80 (1.26, 2.58)) and reproductive-age women (4.32 (2.49, 7.47)) with high trajectory of C-index, the DM risk decreased after adjustment. Conclusions: The risk of DM was greater for high BMI, WC, C-index, and BRI trajectories than for lower trajectories. Hence, the development of general, abdominal, and visceral obesity trajectories in the prevention of DM should be considered by clinicians. [ABSTRACT FROM AUTHOR]

Obesity is a multifactorial metabolic disorder associated with endothelial dysfunction and increased risk of cardiovascular disease. Adipose capillary adipose endothelial cells (CaECs) plays a crucial role in lipid transport and storage. Here, we investigated the mechanisms underlying CaEC-adipocyte interaction and its impact on metabolic function. Single-cell RNA sequencing (scRNAseq) revealed an enrichment of fatty acid handling machinery in CaECs from high fat diet (HFD) mice, suggesting their specialized role in lipid metabolism. Transmission electron microscopy (TEM) confirmed direct heterocellular contact between CaECs and adipocytes. To model this, we created an in vitro co-culture transwell system to model the heterocellular contact observed with TEM. Contact between ECs and adipocytes in vitro led to upregulation of fatty acid binding protein 4 in response to lipid stimulation, hinting intercellular signaling may be important between ECs and adipocytes. We mined our and others scRNAseq datasets to examine which connexins may be present in adipose capillaries and adipocytes and consistently identified connexin 43 (Cx43) in mouse and humans. Genetic deletion of endothelial Cx43 resulted in increased epididymal fat pad (eWAT) adiposity and dyslipidemia in HFD mice. Consistent with this observation, phosphorylation of Cx43 at serine 368, which closes gap junctions, was increased in HFD mice and lipid-treated ECs. Mice resistant to this post-translational modification, Cx43S368A, were placed on an HFD and were found to have reduced eWAT adiposity and improved lipid profiles. These findings suggest Cx43-mediated heterocellular communication as a possible regulatory mechanism of adipose tissue function. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: Anthropometry and body mass index (BMI) do not assess body composition or its distribution in older adults; thus, individuals may have different fat percentages but similar BMI values. The body adiposity index (BAI) was recently proposed as a feasible and inexpensive method for estimating the percentage of body fat based on measurements of hip circumference and height. The present study evaluated whether BAI and BMI are useful alternatives to dual-energy X-ray absorptiometry (DXA), which is rarely used in clinical practice, for predicting body fat in independent long-lived older adults. Methods: In this cross-sectional study, we used DXA to calculate the percentage of body fat, which was compared with BAI and BMI values. We performed Pearson correlation analyses and used Cronbach's alpha, described by Bland and Altman, to compare the reliability between the indexes. Results: Among 157 evaluated individuals (73.2% women, mean age 87±3.57 years), men had a lower percentage of total fat, as assessed by DXA, and lower BAI indices than women. The correlation between BAI and DXA was moderate (r=0.59 for men and r=0.67 for women, p<0.001). We confirmed the reliability based on Cronbach's alpha coefficients of 0.67 in men and 0.77 in women. We also observed that the BAI was strongly positively correlated with BMI in both men and women. Conclusion: The BAI, used in combination with BMI, can be an alternative to DXA for the assessment of body fat in the oldest old in clinical practice, mainly women, and can be used to add information to BMI. [ABSTRACT FROM AUTHOR]

Purpose: To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. Methods: The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. Results: Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. Conclusion: Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk. [ABSTRACT FROM AUTHOR]

Summary: Considering the current prevalence in obesity and sarcopenia globally, this study aimed to summarize the development of sarcopenic obesity research to establish the topic's past, present, and future research direction using a bibliometric analysis. A comprehensive search for publications on sarcopenia and obesity was conducted in the Web of Science (WoS) database until the 31st of December 2023. We performed a detailed descriptive analysis, considering metrics like sources, authors, and documents, along with analyzing conceptual and social structures to map sarcopenic obesity research. Between 1993 and 2023, there were 4978 publications on sarcopenic obesity, representing 22.6% of the whole sarcopenia research (22070). Most published articles were originals (74.6%), and one of the highest increments in the fields was seen after 2010. The most significant contribution in this research area falls under the categories of Nutrition & Dietetics, Gerontology, and Geriatrics & Gerontology. Among regions, scientific production was located in 93 different countries. The United States, China, and South Korea had the highest contributions. The most relevant keywords were sarcopenia, obesity, and body composition. Research on sarcopenic obesity primarily focuses on epidemiology and identifying risk factors and outcome predictors. Yet, there is a shortage of research addressing prevention, early detection, and treatments to enhance the health of individuals with sarcopenia. [ABSTRACT FROM AUTHOR]

Summary: Objective: This study identified metabolite modules associated with adiposity and body fat distribution in childhood using gold‐standard measurements. Methods: We used cross‐sectional data from 329 children at mid‐childhood (age 5.3 ± 0.3 years; BMI 15.7 ± 1.5 kg/m2) from the Genetics of Glucose regulation in Gestation and Growth (Gen3G), a prospective pre‐birth cohort. We quantified 1038 plasma metabolites and measured body composition using the gold‐standard dual‐energy x‐ray absorptiometry (DXA), in addition to skinfold, waist circumference, and BMI. We applied weighted‐correlation network analysis to identify a network of highly correlated metabolite modules. Spearman's partial correlations were applied to determine the associations of adiposity with metabolite modules and individual metabolites with false discovery rate (FDR) correction. Results: We identified a 'green' module of 120 metabolites, primarily comprised of lipids (mostly sphingomyelins and phosphatidylcholine), that showed positive correlations (all FDR p < 0.05) with DXA estimates of total and truncal fat (ρadjusted = 0.11–0.19), skinfold measures (ρadjusted = 0.09–0.26), and BMI and waist circumference (ρadjusted = 0.15 and 0.18, respectively). These correlations were similar when stratified by sex. Within this module, sphingomyelin (d18:2/14:0, d18:1/14:1)*, a sphingomyelin sub‐specie that is an important component of cell membranes, showed the strongest associations. Conclusions: A module of metabolites was associated with adiposity measures in childhood. [ABSTRACT FROM AUTHOR]

Aim: Higher adiposity and increased risk of cardiovascular diseases have been reported in juvenile idiopathic arthritis (JIA), but body composition measurements have produced inconsistent results. This controlled cross‐sectional study assessed body composition with two methods to evaluate adiposity in children with JIA. Methods: We measured body composition by dual‐ energy X‐ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) from 79 JIA‐patients in two Finish university hospitals in 2017–2019. Their age‐ and sex‐matched controls (n = 79) were selected from the Physical Activity and Nutrition in Children‐ study and through National Registry. Results: Body fat percentage measured by BIA was higher (mean, SD) in patients compared to controls (23.1 ± 9.3% vs. 20.1 ± 7.5%, p = 0.047). Also, using DXA, there was a tendency of higher body fat percentage in patients (27.1 ± 9.1% vs. 24.6 ± 8.6, p = 0.106). BIA and DXA showed strong correlation (r from 0.810 to 0.977) in all body composition variables. Conclusion: Increased adiposity was observed in patients with JIA. Evaluation of body composition should be included in the multidisciplinary care of JIA to reduce the possible risk of cardiovascular diseases in adulthood. BIA could be a useful tool for assessing body composition due to its clinical availability and safety. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cardiac magnetic resonance imaging (CMR)–defined ventricular scar and anatomic conduction channels (CMRCCs) offer promise in delineating ventricular tachycardia substrate. No studies have validated channels with coregistered histology, nor have they ascertained the histological characteristics of deceleration zones (DZs) within these channels. We aimed to validate CMR scar and CMR-CCs with whole-heart histology and electroanatomic mapping in a postinfarction model. METHODS: Five sheep underwent anteroseptal infarction. CMR (116±20 days post infarct) was postprocessed using ADAS-3D, varying pixel intensity thresholds (5545, 6040, 6535, and 7030). DZs were identified by electroanatomic mapping (129±12 days post infarct). Explanted hearts were sectioned and stained with Picrosirius red, and whole-heart histopathologic shells were generated. Scar topography as well as percentage fibrosis, adiposity, and remaining viable myocardium within 3 mm histological biopsies and within CMR-CCs were determined. RESULTS: Using the standard 6040 thresholding, CMR had 83.8% accuracy for identifying histological scar in the endocardium (κ, 0.666) and 61.4% in the epicardium (κ, 0.276). Thirty-seven CMR-CCs were identified by varying thresholding; 23 (62%) were unique. DZs colocalized to 19 of 23 (83%) CMR-CCs. Twenty (87%) CMR-CCs were histologically confirmed. Within-channel histological fibrosis did not differ by the presence of DZs (P=0.242). Within-channel histological adiposity was significantly higher at sites with versus without DZs (24.1% versus 8.3%; P<0.001). CONCLUSIONS: Postprocessed CMR-derived scars and channels were validated by histology and electroanatomic mapping. Regions of CMR-CCs at sites of DZs had higher adiposity but similar fibrosis than regions without DZs, suggesting that lipomatous metaplasia may contribute to arrhythmogenicity of postinfarction scar. [ABSTRACT FROM AUTHOR]

Adiposity is a chronic disease that must be treated from childhood. Despite the transcendence of improving habits, few interventions report their contribution to decreasing adiposity. Methods: This cohort enrolled children and teens of any gender, 8–18 years old, and with a body mass index (BMI) z-score of ≥1 into "Sacbe", a comprehensive program to identify which eating habits could reduce BMI z-score. The sample size calculated was 110 participants. We recorded anthropometric measures, clinical history, and habits. A clinically relevant reduction in BMI z-score was defined as ≥0.5 over 12 months or its equivalent according to the months of follow-up. Results: 58.2% were female, the median age was 12 years (range: 9.1–14.7), and the mean BMI z-score was 2.30 ± 0.83. The 82.7% achieved a reduced BMI z-score but 41.8% achieved a clinically relevant reduction with a median follow-up of 6.7 months. Eating out less than once per week was associated with this outcome, even after adjusting for energy intake, other eating patterns, sedentary screen time, physical activity, sleep duration, and sitting time (HR 2.12; 95% CI: 1.07–4.21). Conclusions: Eating out < once/week implicates less processed food exposition and better quality of food; this habit could be the most effective to reduce childhood adiposity. [ABSTRACT FROM AUTHOR]

Background: The interaction between physical activity, skeletal muscle health, and adiposity has been explored in normal weight and overweight/obesity grouped together; however, the overall risks associated with being overweight are less than those observed with obesity and can be confounded by disparities in both sex and race. Thus, the present study sought to investigate the intricate interplay of daily physical activity and skeletal muscle oxidative capacity (SMOC) in overweight and obesity, while exploring how sex and race impact this dynamic relationship. Methods: One hundred and forty participants were grouped by body mass index (BMI) as overweight (n = 73; BMI >25–<30 kg/m2) or obese (n = 67; BMI ≥30 kg/m2). SMOC was assessed using near‐infrared spectroscopy and daily physical activity was assessed for 7 days using accelerometry. Results: Overweight individuals exhibited a higher (p = 0.004) SMOC and engaged in more (p = 0.007) vigorous physical activity compared to obese individuals. In addition, SMOC was lower (p = 0.005) in obese non‐Hispanic Black (NHB) men compared to overweight NHB men. No relationships between physical activity and SMOC were observed. Conclusion: Physical activity is not associated with differences in SMOC in overweight and obesity. Obese individuals engage in less vigorous physical activity and exhibit lower SMOC compared to overweight individuals and these differences are emphasised in NHB men. [ABSTRACT FROM AUTHOR]

Background: To assess the association of adverse pregnancy and infant outcomes with different cut-off levels of glucose intolerance during pregnancy in the MAASTHI cohort. Design: Pregnant women (n = 1470) underwent Oral glucose tolerance test between 24 and 36 weeks using a 75-g oral glucose load, with plasma glucose estimations measured at fasting and two hours later. Follow-up was done within 72 hours of delivery for recording type of delivery, infant weight, mid-upper arm circumference, and skinfold thickness. Results: The odds of having higher skinfold thickness (> 90th percentile) were 43% higher (AOR = 1.43; 95% CI: 1.18, 1.74) and the odds of being overweight at birth was 34% higher (AOR = 1.34; 95% CI: 1.09, 1.62) for every 1 standard deviation (9.9 mg/dL) increase in fasting plasma glucose (FPG) in male infants. The odds of delivering via caesarean section were 45% higher in women with female foetus (1.45,95% CI 1.15,1.82) for every one SD (23.4 mg/dl) increase in 2-h post-load Glucose. Conclusion: The impact of maternal glucose levels on infant and maternal outcomes differed notably between sex of the child. Compared to female infants, male infants exhibited a stronger association with elevated risks for adverse outcomes, including higher infant weight and increased skinfold thickness. Plain Language Summary: Glucose intolerance, in simple terms, refers to a condition where the body has difficulty processing sugar (glucose) properly. Normally, when we eat, our body breaks down carbohydrates into glucose, which is then used by cells for energy. However, in glucose intolerance, this process does not work as efficiently. This can lead to higher-than-normal blood sugar levels, which, if persistent, can increase the risk of developing type 2 diabetes over time. In this study, the researchers investigated how glucose intolerance during pregnancy results in negative health outcomes in mothers and infants in a South Indian City. This is significant as the adverse impact of glucose intolerance in Indian women is not widely studied. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was considered by WHO for defining GDM diagnosis primarily focused on Caucasian populations. Given the known ethnic differences in glucose metabolism and the high prevalence of gestational diabetes in India, understanding glucose intolerance, specifically in Indian women, is essential. In this research, all pregnant mothers underwent an oral glucose tolerance test between the 24th and 36th weeks of pregnancy. They fasted for 12 hours before their blood samples were taken to measure their fasting glucose levels. Then, they drank a glucose solution containing 75 g of glucose. After waiting for 2 hours, their glucose levels were measured again. Those with fasting glucose levels equal to or greater than 92 mg/dl and 2-hour post-load plasma glucose levels equal to or greater than 153 mg/dl were diagnosed with gestational diabetes mellitus (GDM). After delivery, the weight and fat deposition under the skin; known as skinfold thickness (adiposity) were measured using a skinfold caliper. The risks of higher weight and skinfold were seen in male infants compared to female infants. The overall risk of adiposity and C-section were higher than those reported in the HAPO study, highlighting the need for large-scale studies among the Indian population to better understand and address these associations. [ABSTRACT FROM AUTHOR]

The prevalence of overweight and obesity increases in people with type 1 diabetes (T1D). However, the impact of fat accumulation on glucose dynamics in T1D is poorly understood. We assessed continuous glucose monitoring (CGM) parameters in patients with T1D depending on their body weight, body composition, and insulin sensitivity. In 547 patients, including 238 overweight/obese individuals, CGM-derived time in range (TIR) and glucose variability (GV) were estimated. Body composition was assessed by DXA. Estimated glucose disposal rate (eGDR) was used as an indicator of insulin sensitivity. Overweight/obese patients, when compared to normal-weight ones, have a lower time below range (TBR) (<3 mmol/L), GV, and experienced fewer episodes of low glucose. In men, lower TIR, higher time above range (TAR), and GV reduction were associated with central adiposity assessed by total, trunk, and android fat mass. In women, gynoid fat mass only was associated with a lower TIR and higher TAR. The eGDR was a positive predictor of TIR and a negative predictor of TAR, TBR, and GV in men and women. In conclusion, adiposity in people with T1D is associated with a lower risk of CGM-confirmed hypoglycemia, higher TAR, and reduced GV. These features of daily glucose dynamics may be mediated by insulin resistance. [ABSTRACT FROM AUTHOR]

Context Surrogate measures of childhood and adolescent obesity have impaired the understanding of the relationship of body composition with insulin resistance in the young population. Objective We aim to examine the longitudinal associations of directly measured total fat mass, trunk fat mass, and lean mass with the risk of hyperglycemia, hyperinsulinemia, and insulin resistance from ages 15 to 24 years, the mediation path through which lipids and inflammation influence insulin resistance, and whether increased fat mass temporally precede insulin resistance. Methods We studied 3160 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, who had complete dual-energy x-ray absorptiometry measure and fasting blood samples at age 15 years and repeated measures at ages 17- and 24-years clinic visit. Fasting glucose greater than 6.1 mmol/L, insulin greater than 11.78 mU/L, and homeostatic model assessment for insulin resistance (HOMA-IR) greater than or equal to the 75th percentile were categorized as hyperglycemia, hyperinsulinemia, and high insulin resistance, respectively. Longitudinal associations were examined with generalized logit-mixed-effect models, while mediation and temporal path analyses were examined using structural equation models, adjusting for cardiometabolic and lifestyle factors. Results Among 3160 participants (51% female), fat mass and lean mass increased linearly both in males and females, while glucose, insulin, and HOMA-IR had a U-shaped course from age 15 through 24 years. After full adjustment, each 1-kg cumulative increase in total fat mass (odds ratio 1.12 [95% CI, 1.11-1.13]) and trunk fat mass (1.21 [1.19-1.23]) from ages 15 through 24 years were associated with a progressively worsening risk of high insulin resistance as well as hyperglycemia and hyperinsulinemia. The association of increased total fat mass with increased insulin resistance was partly mediated by triglycerides (9% mediation). In the temporal path analysis, higher total fat mass at age 15 years was associated with higher insulin resistance at age 17 years, but not vice versa. Higher total fat mass at age 17 years was bidirectionally associated with higher insulin resistance at 24 years. Conclusion Mid-adolescence may be an optimal time for interrupting the worsening fat mass–insulin resistance pathologic cycle and attenuating the risk of progressively worsening metabolic dysfunction before young adulthood. [ABSTRACT FROM AUTHOR]

BackgroundFindings on the associations between prenatal PFAS exposures and offspring adiposity are inconsistent. Whether such associations may extend to adolescence is especially understudied.ObjectivesWe investigated associations of prenatal PFAS exposures with offspring adiposity and body composition at 16-20 years of age.MethodsWe studied 545 mother-child pairs in the prospective prebirth cohort Project Viva (Boston, Massachusetts). We measured six PFAS (PFOA, PFOS, PFNA, PFHxS, EtFOSAA, and MeFOSAA) in maternal early pregnancy (median age=9.6wk, range: 5.7-19.6 wk) plasma samples. At the late adolescence visit (median age=17.4 y, range: 15.9-20.0 y), we obtained anthropometric measures and assessed body composition using bioelectrical impedance analysis and dual-energy X-ray absorptiometry. We examined associations of individual PFAS with obesity [i.e., age- and sex-specific body mass index (BMI) ≥95th percentile] and adiposity and body composition using multivariable Poisson and linear regression models, respectively. We assessed PFAS mixture effects using Bayesian kernel machine regression (BKMR) and quantile g-computation. We used fractional-polynomial models to assess BMI trajectories (at 3-20 years of age) by prenatal PFAS levels.ResultsThirteen percent (n=73) of the children had obesity in late adolescence. After multivariable adjustment, higher prenatal PFAS concentrations were associated with higher obesity risk [e.g., 1.59 (95% CI: 1.19, 2.12), 1.24 (95% CI: 0.98, 1.57), and 1.49 (95% CI: 1.11, 1.99) times the obesity risk per doubling of PFOS, PFOA, and PFNA, respectively]. BKMR showed an interaction between PFOA and PFOS, where the positive association between PFOS and obesity was stronger when PFOA levels were lower. Each quartile increment of the PFAS mixture was associated with 1.52 (95% CI: 1.03, 2.25) times the obesity risk and 0.52 (95% CI: -0.02, 1.06) kg/m2 higher BMI. Children with higher prenatal PFOS, EtFOSAA, and MeFOSAA concentrations had higher rates of BMI increase starting from 9-11 years of age.DiscussionPrenatal PFAS exposures may have obesogenic effects into late adolescence. https://doi.org/10.1289/EHP12597.

Abstract Background Bisphenol S (BPS) is the main substitute for bisphenol A (BPA), a well-known plasticiser and endocrine disruptor. BPS disrupts ovarian function in several species. Moreover, a few studies have reported that the effects of BPS might be modulated by the metabolic status, and none have characterised the granulosa cell (GC) proteome after chronic BPS exposure. Objectives This study aimed to decipher the mechanisms of action of chronic BPS exposure on the proteome of ewe GCs while considering the interaction between a deliberate contrasted metabolism and reproductive function. Methods Forty ewes were split into two groups with contrasted diets: restricted (R, n = 20) and well-fed (WF, n = 20). The R and WF ewes were subdivided according to the dose of BPS administered through the diet (0–50 µg/kg/day), forming four groups: R0, R50, WF0 and WF50. After 3-month BPS daily exposure, GCs were recovered during the pre-ovulatory stage and proteins were analysed by nano-liquid chromatography coupled with tandem mass spectrometry. Results Chronic exposure to BPS affected the GC proteome differently according to the ewe metabolic status. Fifty-nine out of 958 quantified proteins were differentially abundant between groups and are mainly involved in carbohydrate and lipid pathways. Unsupervised hierarchical clustering of differentially abundant proteins (DAPs) identified four clusters of 34, 6, 5 and 14 proteins according to the BPS exposure and diet interaction. Pairwise comparisons between groups also revealed a strong effect of BPS exposure and diet interaction. Functional analysis of DAPs highlighted that BPS upregulated β-glucuronidase (GUSB; p = 0.002), a protein especially able to deconjugate bisphenol glucuronides (BP-g). Moreover, among unexposed ewes, GUSB was detected only in well-fed ewes. Discussion Conjugation of glucuronides inhibits the oestrogenic activity of bisphenols. Upregulation of GUSB in ewes dosed with BPS would prolong the oestrogenic effects of BPS by deconjugating BPS-g into free BPS. In addition, literature has reported an up-regulation of GUSB in people suffering from obesity. Therefore, people suffering from obesity could be subjected to prolonged and aggravated exposure to BPS. These data highlighted the deleterious effects of BPS and its interaction with metabolic status.