Risk Of Metabolic Diseases Research Articles

The pulse of sleep: novel interventions in understanding the sleep-cardiovascular connection: a literature review.

Sleep disorders represent common complaints in different medical illnesses. They encompass a risk for diverse inflammatory, metabolic, and cardiovascular diseases. Sleep disorders include disorders of hypersomnolence, insomnia, parasomnias, sleep-related movement disorders, circadian rhythm sleep-wake-disorders, and sleep-related breathing disorders, each one of which was associated with increased cardiovascular disease risk in a different mechanism. In this review, the authors address the most recent research on the correlation between sleep and CVD. The literature on sleep disorders and their potential links to various cardiovascular diseases was reviewed in narrative form. For the published papers up to June 2023, the authors searched the databases of PubMed and Google Scholar. Literature demonstrating the relationship between these illnesses, pathophysiological mechanisms, diagnosis, and various therapeutic approaches was included. Sleep disorders were significantly linked to heart rate variability, hypertension, and obesity, which can eventually result in cardiovascular consequences and affect mortality and morbidity. The disruption in sleep cycles, which can be noticed in different sleep disorders, can obviously result in blood pressure, heart rate, and other cardiac functions. The clinical assessment acts as the cornerstone in the diagnosis of different spectrums of sleep disorders. The management of sleep disorders ranges from cognitive-behavioral therapy to continuous positive airway pressure (CPAP). Additional research on the topic is needed to pinpoint any potential links and pathological processes. To improve clinical treatment and preventive measures, further observational studies should emphasize the reliability of early diagnostic signs.

Lipolysis pathways modulate lipid mediator release and endocannabinoid system signaling in dairy cows’ adipocytes

BackgroundAs cows transition from pregnancy to lactation, free fatty acids (FFA) are mobilized from adipose tissues (AT) through lipolysis to counter energy deficits. In clinically healthy cows, lipolysis intensity is reduced throughout lactation; however, if FFA release exceeds tissue demands or the liver’s metabolic capacity, lipid byproducts accumulate, increasing cows’ risk of metabolic and infectious disease. Endocannabinoids (eCBs) and their congeners, N-acylethanolamines (NAEs), are lipid-based compounds that modulate metabolism and inflammation. Their synthesis and release depend upon the availability of FFA precursors and the abundance of synthesizing and degrading enzymes and transporters. Therefore, we hypothesized that eCB production and transcription of endocannabinoid system components are modulated by lipolysis pathways in adipocytes. To test this hypothesis, we stimulated canonical (isoproterenol, 1 µmol/L; ISO) and inflammatory (lipopolysaccharide, 1 µg/mL; LPS) lipolysis pathways in adipocytes isolated from the AT of 5 Holstein dairy cows. Following, we assessed lipolysis intensity, adipocytes’ release of eCBs, and transcription of endocannabinoid system components.ResultsWe found that ISO and LPS stimulated lipolysis at comparable intensities. Exposure to either treatment tended to elevate the release of eCBs and NAEs by cultured adipocytes; however, specific eCBs and NAEs and the transcriptional profiles differed by treatment. On one hand, ISO enhanced adipocytes’ release of 2-arachidonoylglycerol (2-AG) but reduced NAE production. Notably, ISO enhanced the cells’ expression of enzymes associated with 2-AG biosynthesis (INPP5F, GDPD5, GPAT4), transport (CD36), and adipogenesis (PPARG). Conversely, LPS enhanced adipocytes’ synthesis and release of N-arachidonoylethanolamide (AEA). This change coincided with enhanced transcription of the NAE-biosynthesizing enzyme, PTPN22, and adipocytes’ transcription of genes related to eCB degradation (PTGS2, MGLL, CYP27B1). Furthermore, LPS enhanced adipocytes’ transcription of eCB and NAE transporters (HSPA1A, SCP2) and the expression of the anti-adipogenic ion channel, TRPV3.ConclusionsOur data provide evidence for distinct modulatory roles of canonical and inflammatory lipolysis pathways over eCB release and transcriptional regulation of biosynthesis, degradation, transport, and ECS signaling in cows’ adipocytes. Based on our findings, we conclude that, within adipocytes, eCB production and ECS component expression are, at least in part, mediated by lipolysis in a pathway-dependent manner. These findings contribute to a deeper understanding of the molecular mechanisms underlying metabolic regulation in dairy cows’ AT, with potential implications for prevention and treatment of inflammatory and metabolic disorders.Graphical

Dual Use of Cannabis with Tobacco Is Associated with Increased Sugary Food and Drink Intake in Young People.

Rates of cannabis initiation among teenagers and young adults are increasing. Further, the use of various forms of cannabis (smoked or vaped) with nicotine (dual use) is increasingly common among young people. The health effects of dual use are lesser known, particularly in the context of high-potency cannabis products and across different routes of administration, which is ominous in terms of predicting future health outcomes. There is a long history of cannabis use being associated with decreased activity and increased snacking, both of which could portend an increased risk of metabolic and cardiovascular disease, particularly when these habits begin during formative years. However, modern forms of cannabis may not have these same effects. Here, we assess whether cannabis use alone and dual use of cannabis with nicotine impact dietary and exercise habits in young people. An anonymous, social media-based survey was designed based on the UC San Diego Inhalant Questionnaire and published diet and exercise questionnaires. A total of 457 surveys were completed. Young sole cannabis users represented 29% of responders, 16% were dual users of cannabis and nicotine, and 55% were non-users of either drug. Although the sole use of cannabis was not associated with dietary or activity differences relative to non-users, dual users of cannabis and nicotine reported higher consumption of unhealthy sugars. This novel finding of dual use being associated with increased sugar intake in young people raises concerns for an increased risk of metabolic syndrome and cardiovascular disease in this population.

Effect of Immunosuppressive Regimens on Metabolic Dysfunction-associated Fatty Liver Disease Following Liver Transplantation

BackgroundMetabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored. MethodsA retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease. ResultsA total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of post-transplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15∼0.90, P = 0.021) and a combination of tacrolimus and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01∼2.77, P = 0.046) were associated with lower risk of post-transplant metabolic dysfunction-associated fatty liver disease. ConclusionsOur study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus and sirolimus-based immunosuppressive regimen can effectively lower the risk of post-transplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases

Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68). Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

Maternal Innate Immune Reprogramming After Complicated Pregnancy.

Preeclampsia (PE) and fetal growth restriction (FGR) are often associated with maternal inflammation and an increased risk of cardiovascular and metabolic disease in the affected mothers. The mechanism responsible for this increased risk of subsequent disease may involve reprogramming of innate immune cells, characterized by epigenetic modifications. Circulating monocytes from women with PE, FGR, or uncomplicated pregnancies (control) were isolated before labor. Cytokine release from monocytes following exposure to lipopolysaccharide (LPS) and the presence of lysine 4-trimethylated histone 3 (H3K4me3) within TNF promoter sequences were evaluated. Single-cell transcriptomic profiles of circulating monocytes from women with PE or uncomplicated pregnancies were assessed. Monocytes from women with PE or FGR exhibited increased IL-10 secretion and decreased IL-1β and GM-CSF secretion in response to LPS. While TNFα secretion was not significantly different in cultures of control monocytes versus those from complicated pregnancies with or without LPS exposure, monocytes from complicated pregnancies had significantly decreased levels of H3K4me3 associated with TNF promoter sequences. Cluster quantification and pathway analysis of differentially expressed genes revealed an increased proportion of anti-inflammatory myeloid cells and a lower proportion of inflammatory non-classical monocytes among the circulating monocyte population in women with PE. Monocytes from women with PE and FGR exhibit an immune tolerance phenotype before initiation of labor. Further investigation is required to determine whether this tolerogenic phenotype persists after the affected pregnancy and contributes to increased risk of subsequent disease.

Fasting and calorie restriction modulate age‐associated immunosenescence and inflammaging

AbstractAging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age‐associated disease. Genetic manipulation of the nutrient‐sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age‐associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population.

Correlation analysis of occupational stress and metabolic syndrome among employees of a power grid enterprise in China.

Being in a state of high occupational stress may disrupt the metabolic balance of the body, thus increasing the risk of metabolic diseases. However, the evidence about the relationship between occupational stress and metabolic syndrome was limited. To explore the association between occupational stress and metabolic syndrome (MetS) in employees of a power grid enterprise. A total of 1091 employees were recruited from a power grid enterprise in China. Excluding those who failed to complete the questionnaire and those who had incomplete health check-ups, 945 subjects were included in the study. Assessment of occupational stress was used by job demand-control (JDC) and effort-reward imbalance (ERI) questionnaires, respectively. The information on body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were collected. The levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and fasting blood glucose (FBG) in the fasting venous blood samples were measured. Logistic regression analysis and multiple linear regression methods were used to analyze the correlation between JDC and ERI models of occupational stress, metabolic syndrome, and its components, respectively. The prevalence of MetS was 8.4% and 9.9% in JDC and ERI model high occupational stress employees, respectively. ERI model occupational stress and smoking are significantly associated with the risk of MetS. ERI ratio was significantly associated with lower HDL-C levels. Gender, age, marital status, smoking, high-temperature and high-altitude work were significantly associated with metabolic component levels. Our study revealed a high detection rate of occupational stress in both JDC and ERI models among employees of a power grid enterprise. ERI model occupational stress, demanding more attention, was associated with the risk of MetS as well as its components such as HDL-C.

Pre-pregnancy shift work’s influence on postpartum weight retention: Body mass index’s role

ABSTRACT Shift work is a prevalent workplace exposure, which increases the possibility of unhealthy behaviours and circadian rhythm disruptions and elevates the risk of metabolic diseases and adverse reproductive outcomes. But its potential of increasing the risk of postpartum weight retention remains uncertain. This study aimed to investigate the association between maternal shift work prior to conception and postpartum weight retention, and to identify modifiable factors during pregnancy for prevention. We analysed data from the Taiwan Birth Cohort Study, a prospective cohort of Taiwanese women who gave birth in 2005. We examined the pre-conceptional shift work status of 13,575 mothers and their body weight before pregnancy, before delivery, six and eighteen months after delivery. We used multivariable linear models to examine associations and effect modifications. Maternal shift work before pregnancy was significantly associated with increased postpartum weight retention at six and eighteen months (β-estimate for six months: 0.19-kilogram, 95% CI: 0.03–0.34; eighteen months: 0.23-kilogram, 95% CI: 0.04–0.40). The association between shift work and weight retention at six months postpartum was stronger among mothers who were overweight or obese before pregnancy than mothers with normal weight. This study showed the impact of shift work on postpartum weight retention and suggested a stronger association among mothers with overweight or obesity before pregnancy.

Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases

BackgroundExposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease.MethodsNMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases.ResultsPrenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2–0.3 SD, p < 3 × 10−3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r = 0.77, p = 3 × 10−27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1 × 10−18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2 × 10−4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index.ConclusionsPrenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.

An exploratory analysis of the metabolic syndrome and cardiovascular disease risk calculations in veterans with spinal cord injury and disorders

Objectives (1) To describe and compare cardiovascular and cardiometabolic disease risk scores using three existing risk calculators: Framingham Risk Score (FRS), American Heart Association (AHA) and Metabolic Syndrome Severity Score (MSSS) in Veterans with spinal cord injury and disorders (SCI/D); (2) To examine level of agreement between risk scores derived from three different risk scoring systems; and (3) To investigate whether the agreement among these methods is different for Veterans with Tetraplegia versus Paraplegia. Design Retrospective chart review. Methods Electronic medical records of 194 Veterans with SCI/D who were seen at the VAPAHCS SCI/D Center between August 2004 and June 2022 were reviewed. Cardiovascular disease (CVD) risk scores (FRS and AHA) along with a Metabolic Syndrome Severity Score (MSSS) were computed using web-based calculators. Results Moderate agreement between CVD risk scores (FRS and AHA) was observed; however, the agreement was poor between MSSS and both AHA and FRS. No differences were observed between the paraplegia and tetraplegia cohorts. From the AHA risk score, more than half the study population was found to be at high risk while less than half was considered high risk from the FRS and MSSS scores. Conclusions Given the moderate association between AHA and FRS scores along with considerable variation in risk predictors, CVD risk prediction assessment tools should be interpreted cautiously in the SCI population. SCI-related clinical biomarkers and other clinically relevant risk factors should be taken into consideration to optimize risk estimation in persons with SCI/D.

Free fatty acids induce bile acids overproduction and oxidative damage of bovine hepatocytes via inhibiting FXR/SHP signaling

Hepatic oxidative injury induced by free fatty acids (FFA) and metabolic disorders of bile acids (BA) increase the risk of metabolic diseases in dairy cows during perinatal period. However, the effects of FFA on BA metabolism remained poorly understood. In present study, high concentrations of FFA caused cell impairment, oxidative stress and BA overproduction. FFA treatment increased the expression of BA synthesis-related genes [cholesterol 7a-hydroxylase (CYP7A1), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7, sterol 12α-hydroxylase, sterol 27-hydroxylase and oxysterol 7α-hydroxylase], whereas reduced BA exportation gene (ATP binding cassette subfamily C member 1) and inhibited farnesoid X receptor/small heterodimer partner (FXR/SHP) pathway in bovine hepatocytes. Knockdown of nuclear receptor subfamily 1 group H member 4 (NR1H4) worsened FFA-caused oxidative damage and BA production, whereas overexpression NR1H4 ameliorated FFA-induced BA production and cell oxidative damage. Besides, reducing BA synthesis through knockdown of CYP7A1 can alleviate oxidative stress and hepatocytes impairment caused by FFA. In summary, these data demonstrated that regulation of FXR/SHP-mediated BA metabolism may be a promising target in improving hepatic oxidative injury of dairy cows during high levels of FFA challenges.

Socioeconomic disparities in the postnatal growth of preterm infants: a systematic review.

To determine the effect of parental socioeconomic status (SES) on the postnatal growth of preterm infants. A systematic review (PROSPERO registration CRD42020225714) of original articles from Medline, Embase, CINAHL Plus and Web of Science published 1946-2023 was undertaken. Studies were included if they reported anthropometric growth outcomes for preterm infants according to parental SES. Data extraction and assessments of bias and health equity impact were conducted using custom-designed forms. A narrative synthesis of twelve included studies was performed. Most infants were moderate to late preterm. The settings, growth outcomes, timings of growth measurement, and SES measures were heterogenous. Six studies demonstrated an adverse effect of low parental SES on the extrauterine growth of preterm infants, five studies showed no effect, and one study showed a potentially beneficial effect. All studies had a high risk of bias, especially confounding and selection bias. The health equity impact of included studies was largely negative. Limited and low-quality evidence suggests that socioeconomic minoritisation may adversely impact the growth of preterm infants, thereby widening existing socioeconomic health inequities. Observational studies informed by theorisation of the mechanistic pathways linking socioeconomic minoritisation to adverse postnatal growth are required to identify targets for intervention. Limited evidence suggests low parental socioeconomic status (SES) adversely affects the postnatal growth of preterm infants across different settings. Early growth of preterm infants predicts neurodevelopmental outcomes and the risk of cardiovascular and metabolic disease in adulthood. Systematic screening of over 15,000 articles identified only twelve studies which reported postnatal growth outcomes for preterm infants according to parental SES. The health equity impact of the included studies was systematically assessed, and found to be negative overall. This study highlights limitations in existing evidence on the association between parental SES and postnatal growth, and delineates avenues for future research.

Accurate Prediction of Three-Dimensional Humanoid Avatars for Anthropometric Modeling.

To evaluate the hypothesis that anthropometric dimensions derived from a person's manifold-regression predicted three-dimensional (3D) humanoid avatar are accurate when compared to their actual circumference, volume, and surface area measurements acquired with a ground-truth 3D optical imaging method. Avatars predicted using this approach, if accurate with respect to anthropometric dimensions, can serve multiple purposes including patient metabolic disease risk stratification in clinical settings. Manifold regression 3D avatar prediction equations were developed on a sample of 570 adults who completed 3D optical scans, dual-energy X-ray absorptiometry (DXA), and bioimpedance analysis (BIA) evaluations. A new prospective sample of 84 adults had ground-truth measurements of 6 body circumferences, 7 volumes, and 7 surface areas with a 20-camera 3D reference scanner. 3D humanoid avatars were generated on these participants with manifold regression including age, weight, height, DXA %fat, and BIA impedances as potential predictor variables. Ground-truth and predicted avatar anthropometric dimensions were quantified with the same software. Following exploratory studies, one manifold prediction model was moved forward for presentation that included age, weight, height, and %fat as covariates. Predicted and ground-truth avatars had similar visual appearances; correlations between predicted and ground-truth anthropometric estimates were all high (R2s, 0.75-0.99; all p < 0.001) with non-significant mean differences except for arm circumferences (%D ~ 5%; p < 0.05). Concordance correlation coefficients ranged from 0.80-0.99 and small but significant bias (p < 0.05 - 0.01) was present with Bland-Altman plots in 13 of 20 total anthropometric measurements. The mean waist to hip circumference ratio predicted by manifold regression was non-significantly different from ground-truth scanner measurements. 3D avatars predicted from demographic, physical, and other accessible characteristics can produce body representations with accurate anthropometric dimensions without a 3D scanner. Combining manifold regression algorithms into established body composition methods such as DXA, BIA, and other accessible methods provides new research and clinical opportunities.

Association of second and fourth digit (2D:4D) ratios with metabolic syndrome and cardiovascular disease risk

BackgroundThe study aimed to investigate the association of second and fourth-digit (2D:4D) ratios with metabolic syndrome (MS) and cardiovascular disease risk (CVR). MethodThis case-control study was conducted between February and March 2024 with 200 participants (100 patients +100 controls). Biochemical parameters (glucose, total cholesterol, HDL, LDL, triglycerides, haemogram, HbA1C) were recorded. All participants were evaluated in terms of MS diagnostic criteria. CVR was calculated with the ESC CVD Risk Calculator. Second-digit and fourth-digit measurements were performed and the 2D:4D ratio of both hands and the difference between 2D:4D of both hands (Dr-l) were obtained. The relationship between 2D:4D and MS, CVR, and gender was evaluated. p < .05 was considered statistically significant. ResultsForty-one percent of the study participants were male. The right-hand 2D:4D (R2D:4D) ratio was 1.009 ± 0.04 and the left-hand 2D:4D (L2D:4D) ratio was 0.991 ± 0.04 (p < .001). R2D:4D ratio was 1.010 ± 0.04 in women and 0.985 ± 0.03 in men (p = .019). R2D:4D (p < .001), Dr-l (p = .001), and CVR (p < .001) were significantly higher in men with MS (+) compared to MS (−). ConclusionIn our study, the R2D:4D ratio was found to be associated with MS and CVR in men. Low intrauterine androgen exposure may affect the development of MS, but this effect is more prominent in males.

Maternal Serum Metabolomics in Mid-Pregnancy Identifies Lipid Pathways as a Key Link to Offspring Obesity in Early Childhood.

Maternal metabolism during pregnancy shapes offspring health via in utero programming. In the Healthy Start study, we identified five subgroups of pregnant women based on conventional metabolic biomarkers: Reference (n = 360); High HDL-C (n = 289); Dyslipidemic-High TG (n = 149); Dyslipidemic-High FFA (n = 180); Insulin Resistant (IR)-Hyperglycemic (n = 87). These subgroups not only captured metabolic heterogeneity among pregnant participants but were also associated with offspring obesity in early childhood, even among women without obesity or diabetes. Here, we utilize metabolomics data to enrich characterization of the metabolic subgroups and identify key compounds driving between-group differences. We analyzed fasting blood samples from 1065 pregnant women at 18 gestational weeks using untargeted metabolomics. We used weighted gene correlation network analysis (WGCNA) to derive a global network based on the Reference subgroup and characterized distinct metabolite modules representative of the different metabolomic profiles. We used the mummichog algorithm for pathway enrichment and identified key compounds that differed across the subgroups. Eight metabolite modules representing pathways such as the carnitine-acylcarnitine translocase system, fatty acid biosynthesis and activation, and glycerophospholipid metabolism were identified. A module that included 189 compounds related to DHA peroxidation, oxidative stress, and sex hormone biosynthesis was elevated in the Insulin Resistant-Hyperglycemic vs. the Reference subgroup. This module was positively correlated with total cholesterol (R:0.10; p-value < 0.0001) and free fatty acids (R:0.07; p-value < 0.05). Oxidative stress and inflammatory pathways may underlie insulin resistance during pregnancy, even below clinical diabetes thresholds. These findings highlight potential therapeutic targets and strategies for pregnancy risk stratification and reveal mechanisms underlying the developmental origins of metabolic disease risk.

Insulin-like growth factor-1 infusion in preterm piglets does not affect growth parameters of skeletal muscle or tendon tissue.

Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult-onset metabolic disease. Insulin-like growth factor 1 (IGF-1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect of IGF-1 on extensor carpi radialis muscle and biceps brachii tendon of preterm piglets. The preterm group consisted of 19-day-old preterm (10 days early) piglets, treated with either IGF-1 or vehicle. Term controls consisted of groups of 9-day-old piglets (D9) and 19-day-old piglets (D19). Muscle samples were analysed by immunofluorescence to determine the cross-sectional area (CSA) of muscle fibres, fibre type composition, satellite cell content and central nuclei-containing fibres in the muscle. Tendon samples were analysed for CSA, collagen content and maturation, and vascularization. Gene expression of the tendon was measured by RT-qPCR. Across all endpoints, we found no significant effect of IGF-1 treatment on preterm piglets. Preterm piglets had smaller muscle fibre CSA compared to D9 and D19 control group. Satellite cell content was similar across all groups. For tendon, we found an effect of age on tendon CSA, and mRNA levels of COL1A1, tenomodulin and scleraxis. Immunoreactivity for elastin and CD31, and several markers of tendon maturation, were increased in D9 compared to the preterm piglets. Collagen content was similar across groups. IGF-1 treatment of preterm-born piglets does not influence the growth and maturation of skeletal muscle and tendon.

Food-Borne Polycyclic Aromatic Hydrocarbons and Circadian Disruption.

Circadian disruption has been found to increase the risk of metabolic diseases, brain disorders, and cancer. The aryl hydrocarbon receptor (AhR), responsible for xenobiotic metabolism, is known to be activated by certain environmental stimuli, including polycyclic aromatic hydrocarbons (PAHs). Exposure to these stimuli may lead to diseases related to circadian disruption, with AhR activation suggested as a leading cause. Both the aryl hydrocarbon receptor nuclear translocator (ARNT) and aryl hydrocarbon receptor nuclear translocator-like (BMAL1) are class II basic helix-loop-helix/Per-ARNT-SIM (bHLH-PAS) proteins. These proteins form heterodimers with stimulated class I bHLH-PAS proteins, including circadian locomotor output cycles kaput (CLOCK) and AhR. Due to their sequential similarity, the overactivation of AhR by toxicants, such as PAHs, may lead to the formation of heterodimers with BMAL1, potentially causing circadian disruption. Dysregulation of BMAL1 can affect a wide range of metabolic genes, emphasizing its crucial roles. However, this issue has not been adequately addressed. Previous studies have reported that the inhibitory effects of phytochemicals on AhR activation can ameliorate diseases induced by environmental toxicants. Additionally, some phytochemicals have shown preventive effects on circadian misalignment. Therefore, this Review aims to explore potential strategies to prevent circadian disruption induced by food-borne toxicants, such as benzo[a]pyrene; to generate new ideas for future studies; and to highlight the importance of investigating these preventive strategies.

PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease in youth-a translational research framework.

To address the growing epidemic of liver disease, particularly in pediatric populations, it is crucial to identify modifiable risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology and severity of MASLD remains largely unexplored in humans. This study aims to bridge the gap between human and in vitro studies to understand how exposure to perfluoroheptanoic acid (PFHpA), one of the emerging PFAS replacements which accumulates in high concentrations in the liver, contributes to MASLD risk and progression. First, we showed that PFHpA plasma concentrations were significantly associated with increased risk of MASLD in obese adolescents. Further, we examined the impact of PFHpA on hepatic metabolism using 3D human liver spheroids and single-cell transcriptomics to identify major hepatic pathways affected by PFHpA. Next, we integrated the in vivo and in vitro multi-omics datasets with a novel statistical approach which identified signatures of proteins and metabolites associated with MASLD development triggered by PFHpA exposure. In addition to characterizing the contribution of PFHpA to MASLD progression, our study provides a novel strategy to identify individuals at high risk of PFHpA-induced MASLD and develop early intervention strategies. Notably, our analysis revealed that the proteomic signature exhibited a stronger correlation between both PFHpA exposure and MASLD risk compared to the metabolomic signature. While establishing a clear connection between PFHpA exposure and MASLD progression in humans, our study delved into the molecular mechanisms through which PFHpA disrupts liver metabolism. Our in vitro findings revealed that PFHpA primarily impacts lipid metabolism, leading to a notable increase of lipid accumulation in human hepatocytes after PFHpA exposure. Among the pathways involved in lipid metabolism in hepatocytes, regulation of lipid metabolism by PPAR-a showed a remarkable activation. Moreover, the translational research framework we developed by integrating human and in vitro data provided us biomarkers to identify individuals at a high risk of MASLD due to PFHpA exposure. Our framework can inform policies on PFAS-induced liver disease and identify potential targets for prevention and treatment strategies.

Relationship Between Serum Thyrotropin Levels and Metabolic Diseases in Older Adults.

Subclinical hypothyroidism is associated with metabolic diseases; however, it remains controversial in older individuals. This work aimed to investigate the relationship between thyrotropin (TSH) levels and metabolic diseases. In this cross-sectional study, sampling was conducted from nationally representative general communities from 31 provinces in mainland China. A total of6791 older (aged ≥65 years) and 55 303 young participants (aged 18-64 years) were selected after excluding individuals with overt hyperthyroidism or overt hypothyroidism. According to the kit, TSH reference range (0.27-4.2 mU/L) and the age-specific TSH range previously formulated (an upper limit of 8.86 mU/L for older adults and 6.57 mU/L for young adults), the older adults and young adults were separately divided into 4 groups based on their TSH levels. Main outcome measures included anthropometric assessments, serum concentrations of thyroid functions, and various metabolic parameters. In contrast to young adults, there was no significant increase in the prevalence of any metabolic disorders assessed in the slightly elevated TSH group (TSH 4.21-8.86 mU/L) compared to the euthyroid group (TSH 0.27-4.2 mU/L) among older adults. After adjusting for interference factors, a TSH level higher than 8.86 mU/L was found to be an independent risk factor for low high-density lipoprotein cholesterol (OR, 1.84; 95% CI, 1.14-2.98) and dyslipidemia (OR, 1.49; 95% CI, 1.09-2.04) when compared to the euthyroid group in older adults. Slightly elevated TSH levels are not associated with an increased risk of metabolic diseases in older adults. Therefore, we recommend raising the upper limit of the TSH range for individuals aged 65 years and older.