Risk Of Metabolic Diseases Research Articles

OVERVIEW OF THE DEVELOPMENT OF STUNTING CHILDREN AGED 2-5 YEARS IN GEDOG VILLAGE

Stunting is a growth and development problem that has an impact on intellectual abilities, decreased economic productivity and the risk of metabolic diseases which will affect the development of children in the future. The purpose of this study was to determine the development of stunted children aged 2-5 years in Gedog Village. This research design uses descriptive quantitative with a sample size of 42 stunted children aged 2-5 years who meet the inclusion criteria and are selected using purposive sampling method. Data collection was carried out on February 7-29, 2024 at each integrated healthcare center in Gedog Village. Instruments in the study using the Denver Development Screening Test I and results of the DDST assessment are normal, abnormal, suspect, and unstable. The data obtained is presented in the form of diagrams and narrated. The results of this study were gross motor development 75% scored normal and 25% scored advanced, fine motor development 69% of children were normal, 22% delay and 8% caution, language development 53% normal, 39% caution and 8% delay, personal social development 47% normal, 47% delay and 6% caution and overall normal results 53%, Abnormal 19% and suspect 28%. From these results, it is found that stunting is not the main cause of developmental abnormalities in children. Parenting and the environment are also one of the factors that make children reach their developmental stage.

Prevalence of cardiometabolic outcomes in women who underwent salpingo-oophorectomy to prevent hereditary breast and ovarian cancer: a meta-analysis.

Risk reduction salpingo-oophorectomy (RRSO) is usually performed in women with hereditary breast and ovarian cancer (HBOC) syndrome for BRCA1 and BRCA2 gene mutation carriers, resulting in surgical menopause, which is more associated with a high risk of cardiovascular and metabolic disease than in premenopausal and natural menopausal women. This study assessed the prevalence of cardiovascular and metabolic outcomes in women who underwent salpingo-oophorectomy as a preventive measure against HBOC. This meta-analysis assessed prevalence rates for four metabolic/cardiovascular conditions: myocardial infarction, hypertension, hypercholesterolemia, and type 2 diabetes mellitus. DerSimonian and Laird random-effects models were applied to all analyses, with 95% confidence interval (CI). Heterogeneity was assessed with I². We used OpenMeta Analyst software for statistical analysis. A total of five retrospective studies and one observational study involving 1,320 patients were included. The average body mass index (BMI) was 25.97kg/m2 and the average waist circumference was 87.94cm. The analysis across a mean 4.94-year follow-up revealed prevalence rates for acute myocardial infarction of 1.5% (95% CI 0.3-2.7; P = 0.077; I²=56.25%), hypertension of 28% (95% CI 6.9-49.1; P < 0.001; I2 = 98.42%), hypercholesterolemia of 27.2% (95% CI 6.8-47.6; P < 0.001; I²=98.67%), and type 2 diabetes mellitus of 3.3% (95% CI 1.1-5.5; P < 0.001; I²=82.44%). Our findings suggest that there is no marked increase in cardiovascular risk among women with HBOC undergoing RRSO.

The contribution of attention-deficit/hyperactivity disorder polygenic load to metabolic and cardiovascular health outcomes: a large-scale population and sibling study.

Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers. Furthermore, we investigated to what extent the PGS effect was influenced by direct and indirect genetic effects (i.e., shared familial effects). We derived ADHD-PGS in 50,768 individuals aged 18-90 years from the Dutch Lifelines Cohort study. Using generalised estimating equations, we estimated the association of PGS with cardiometabolic diseases, derived from self-report and several biomarkers measured during a physical examination. We additionally ran within-sibling PGS analyses, using fixed effects models, to disentangle direct effects of individuals' own ADHD genetic risk from confounding due to indirect genetic effects of relatives, as well as population stratification. We found that higher ADHD-PGS were statistically significantly associated with several cardiometabolic diseases (R-squared [R2] range = 0.03-0.50%) and biomarkers (related to inflammation, blood pressure, lipid metabolism, amongst others) (R2 range = 0.01-0.16%) (P < 0.05). Adjustment for shared familial factors attenuated the associations between ADHD-PGS and cardiometabolic outcomes (on average 56% effect size reduction), and significant associations only remained for metabolic disease. Overall our findings suggest that increased genetic liability for ADHD confers a small but significant risk increase for cardiometabolic health outcomes in adulthood. These associations were observable in the general population, even in individuals without ADHD diagnosis, and were partly explained by familial factors shared among siblings.

Lingguizhugan decoction alleviates obesity in rats on a high-fat diet through the regulation of lipid metabolism and intestinal microbiota

BackgroundIndividuals with obesity often experience elevated blood lipid levels, leading to a chronic low-grade inflammatory state, exacerbating liver oxidative stress, and increasing the risk of various metabolic diseases. Recent evidence suggests that intestinal microbiota and short-chain fatty acids (SCFAs) play crucial roles in the development and progression of obesity. While the mechanisms by which Lingguizhugan decoction (LGZGD) intervenes in obesity by improving lipid metabolism, enhancing insulin sensitivity, and reducing inflammatory responses are well-documented, its potential in intestinal microbiota and SCFAs remains unclear. This study aims to explore the impact of LGZGD on high-fat diet (HFD) induced obesity in rats and its regulatory effects on intestinal microbiota and SCFAs, providing new insights for obesity prevention and treatment.MethodsFifty-one male SD rats were randomly divided into groups, with six in the normal control group (NC) receiving a ddH2O treatment and a standard diet. The remaining 45 rats were fed a high-fat diet (HFD) using D12451 feed. After 10 weeks, the rats on the HFD gained 20% more weight than the NC group, confirming the successful modeling of obesity. These rats were then randomly divided into the following groups: ddH2O high-fat diet model group (MC), 20 mg/kg/day Orlistat positive control group (Orlistat), 1.62 g/kg/day low-dose LGZGD group (LGZGL), and 3.24 g/kg/day high-dose LGZGD group (LGZGH) for 8 weeks. We evaluated changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) levels. Fat and liver tissues were collected for pathological analysis. Intestinal contents were aseptically collected for 16S rRNA gene sequencing and gas chromatography–mass spectrometry (GC–MS) to assess gut microbiota and SCFA levels.ResultsLGZGD reduces body weight, TC, TG, LDL, and HDL levels, significantly reducing hepatic steatosis. Besides, it restored the richness and diversity of gut microbiota, which was reduced by HFD, altering the overall structure. Specifically, LGZGD significantly promoted the growth of Muribaculaceae and Dubosiella while inhibiting the growth of Christensenellaceae_R_7_group and UCG_005. It also restricts the production of caproic acid. Correlation analysis indicated positive correlations: Muribaculaceae with Butyric acid and Isovaleric acid; UCG_005 with TC, LDL, and HDL; and Christensenellaceae_R_7_group with TC and LDL.ConclusionLGZGD increased the abundance of beneficial gut microbiota in HFD-induced obese rats, improved gut microbiota dysbiosis, and inhibited the increase in caproic acid content. These results suggest that LGZGD can mitigate HFD-induced obesity, and its active components warrant further investigation.

Resveratrol and Its Derivatives Diminish Lipid Accumulation in Adipocytes In Vitro—Mechanism of Action and Structure–Activity Relationship

Background and Objectives: Expansion of white adipose tissue causes systemic inflammation and increased risk of metabolic diseases due to its endocrine function. Resveratrol was suggested to be able to prevent obesity-related disorders by mimicking caloric restriction; however, its structure–activity relationships and molecular targets are still unknown. We aimed to compare the effects of resveratrol and its analogues on adipocyte metabolism and lipid accumulation in vitro. Methods: Mouse embryonic fibroblasts were differentiated to adipocytes in the absence or presence of resveratrol or its derivatives (oxyresveratrol, monomethylated resveratrol, or trimethylated resveratrol). Intracellular lipid content was assessed by Oil Red O staining. Glucose uptake and its response to insulin were estimated by 2-NBDG, and mitochondrial activity was assayed via resazurin reduction. Involvement of potential molecular pathways was investigated by concurrent treatment with their inhibitors. Results: Although lipid accumulation was significantly reduced by all analogues without altering protein content, oxyresveratrol was the most potent (IC50 = 4.2 μM), while the lowest potency was observed with trimethylated resveratrol (IC50 = 27.4 μM). Increased insulin-stimulated glucose uptake was restored by each analogue with comparable efficiency. The enhanced mitochondrial activity was normalized by resveratrol and its methylated derivatives, while oxyresveratrol had a minor impact on it. Among the examined pathways, inhibition of SIRT1, PGC-1α, and JNK diminished the lipid-reducing effect of the compounds. Autophagy appeared to play a key role in the effect of all compounds but oxyresveratrol. Conclusions: Resveratrol and its analogues can mimic caloric restriction with complex mechanisms, including activation of SIRT1, PGC-1α, and JNK, making them possible drug candidates to treat obesity-related diseases.

Abstract 4134379: Mediterranean-Style Diet and Adverse Pregnancy Outcomes by Race and Overweight or Obesity Status in the Boston Birth Cohort

Introduction: Mediterranean-style diet (MSD) is associated with a lower risk of cardiovascular and metabolic diseases. However, the association of MSD during pregnancy with adverse pregnancy outcomes (APOs) among different racial and ethnic groups and overweight or obesity (OWO) status remains unclear. Question: We examined if MSD during pregnancy is protective for developing any APO and individual APOs in a large cohort of racially and ethnically diverse, urban, low-income women. Methods: Among 8,511 patients in the Boston Birth Cohort (mean age 28.2±6.5 yrs), 47% were non-Hispanic Blacks and 28% were Hispanics. Among 4,343 (51%) with pre-pregnancy OWO status, 25% Black and 12% Hispanic women developed any APO (Figure 1). Individual Mediterranean-style diet score (MDS) was based on maternal diet intake during pregnancy via food frequency questionnaire interviews at 24-72 hours postpartum. Results: Increase in the MDS by one standard deviation was inversely associated with any APO (aOR, 0.86 [95% CI, 0.82–0.90]), preeclampsia or eclampsia or HELLP (aOR, 0.89 [95% CI, 0.82–0.97]), gestational diabetes (aOR, 0.88 [95% CI, 0.81–0.95]), preterm birth (aOR, 0.90 [95% CI, 0.86–0.95]), and low birth weight (aOR, 0.87 [95% CI, 0.83–0.92]) (Table 1). In the subgroup analysis, higher adherence to MSD was associated with lower odds of developing, preeclampsia or eclampsia or HELLP, low birth weight, and preterm birth in Black women with or without OWO. The benefit of MDS was also observed for gestational diabetes in Hispanic women with OWO (Figure 2). Conclusion: Greater adherence to MSD during pregnancy is associated with a lower risk of composite APOs, with benefits varying across types of APOs, racial/ethnic groups, and OWO status.

Effects of Baccharis dracunculifolia DC on an Innovative Animal Model of Cardiometabolic Syndrome

Background/Objective: Cardiometabolic syndrome (CMS) is a complex clinical condition that encompasses metabolic dysregulation, cardiovascular disease, and diabetes risk factors. Worldwide, CMS is underdiagnosed, and its occurrence significantly increases cardiovascular morbimortality. Despite available pharmacological treatments, the approach is fragmented, and the associated clinical conditions are treated independently. This approach may be partially due to limited preclinical models to mimic the clinical conditions of CMS. Therefore, our study aims to present an innovative animal model of cardiometabolic syndrome and evaluate the effects of Baccharis dracunculifolia on the set of clinical alterations associated with the condition. Methods: Female Wistar rats were induced to develop diabetes, fed a cholesterol-enriched diet, and exposed to the smoke of 9 cigarettes/day for 6 weeks. During the last 2 weeks, the rats were treated with vehicle, B. dracunculifolia (30, 100, and 300 mg/kg), or a combination of simvastatin and insulin. At the end of the treatment, plasma lipid levels were measured, and the liver was analyzed histologically for hepatic lipid quantification and oxidative stress assessment. Results: Phytochemical analysis revealed seven phenolic acids and six flavonoids in the extract. B. dracunculifolia showed significant hepatoprotective effects, reducing AST and ALT levels and lowering both plasma and hepatic lipid levels. The extract also reversed hepatic steatosis and demonstrated antioxidant properties. Conclusions: These findings suggest that B. dracunculifolia may be a therapeutic option for the metabolic dysregulation present in CMS.

Association of Changes in Relevant Indicators With Cardiovascular Disease and Osteoporosis in Perimenopausal and Postmenopausal Women

ABSTRACTThe essence of menopause is ovarian failure, decreased estrogen volatility, and deficiency leading to multiple related symptoms and an increased risk of metabolic disease in women, such as cardiovascular disease and osteoporosis. This study screened 773 eligible postmenopausal and perimenopausal women from an initial pool of 1187 participants, and various physiological and biochemical indices were measured and analyzed to assess differences across three age groups (40–44 years, 45–49 years, 50–54). We found no significant difference in the rate of cardiovascular disease between postmenopausal and perimenopausal women, while the rate of osteoporosis was higher in postmenopausal women compared to perimenopausal women. The disease of osteoporosis in postmenopausal women was associated with age (p &lt; 0.05). We also found that postmenopausal women and perimenopausal women had significant effects on follicle‐stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), total cholesterol (TC), lumbar spine BMD (T1), femoral neck BMD, The bone density (T2) of the right femur was significantly affected. There are significant differences in FSH, LH, E2, TC, low‐density lipoprotein (LDL), L2–L4, T1, Neck of femur decrease, and T2 in women of different ages. Furthermore, the correlation analysis between age and E2 and metabolic indicators showed that age has a greater impact on the risk of postmenopausal and perimenopausal females. This study can help further understand the mechanisms of cardiovascular disease and osteoporosis in perimenopausal and menopausal women.

A wearable hip exoskeleton for anaerobic exercise in healthy adults

Guidelines encouraging social distancing, limited outings, and remote work due to COVID-19 have increased sedentary periods and reduced levels of physical activity. These habits increase the risk of metabolic diseases, obesity, cardiovascular disease, and diabetes mellitus. The World Health Organization recommends muscle-strengthening exercises as well as regular physical activity to promote overall health. This study investigates the effect of a wearable hip exoskeleton on muscle activity and heart rate during anaerobic exercise in 40 healthy adults (mean age of 40.00 ± 11.51 years; n = 20 females). Bot Fit, a wearable hip-type robotic exoskeleton, was developed by Samsung Electronics Co., Ltd. (Suwon, Republic of Korea) to enhance the effects of both aerobic and anaerobic exercise. All study participants performed a fitness exercise protocol, including knee-ups, good mornings, squats, mountain climbs, kick-backs, reverse lunges, and split jacks, with and without a Bot Fit. To evaluate the effect of anaerobic exercise with the Bot Fit, muscle activity and heart rate were measured during fitness exercises with and without a Bot Fit. Measured muscles were the rectus abdominis (RA), erector spinae (ES), rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), tibialis anterior (TA), gastrocnemius medialis (GCM), and gluteus maximus (GM). During anaerobic exercises with the Bot Fit, there was a significant increase in muscle activity compared to exercising without the Bot Fit. Muscle activity increased significantly in the RA, RF, VL, BF and TA muscles during knee-ups; in the ES, BF, and GM during good mornings; in the RF, VL, VM, BF, and GM during squats; in RA, RF, VL, VM, and GM during mountain climbs; in the RA and BF during kick-backs; in the RF, BF, and GCM during reverse lunges; and in the RF and VL during split jacks (p < 0.05). Heart rates showed a statistically significant increase during good mornings, mountain climbs, and reverse lunge exercises while wearing the Bot Fit (p < 0.05). This study demonstrated that anaerobic exercises by healthy adults using a Bot Fit led to enhanced activation of abdominal and lower-limb muscles as well as an improved heart rate, maximizing the effect of anaerobic exercise compared with the same exercise protocol without a Bot Fit. This suggests that use of a Bot Fit can increase the effectiveness of anaerobic exercise in healthy adults.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and MACE in patients with established CVD. The clinical value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the clinical value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease (heart failure, coronary artery disease, MASLD, chronic kidney disease). The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels (OR: 1.004, 95% CI:1.000-1.009, P=0.049) and increased triglyceride levels (OR: 1.007, 95%CI: 1.001-1.012, P=0.033) after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score&amp;lt;2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Contaminant Exposure Profiles Demonstrate Similar Physiological Effects Across Environments Despite Unique Profile Composition in Formosa, Argentina, and Connecticut, USA.

Exposure to environmental contaminants is globally universal. However, communities vary in the specific combination of contaminants to which they are exposed, potentially contributing to variation in human health and creating "locally situated biologies." We investigated how environmental exposures differ across environments by comparing exposure profiles between two contexts that differ markedly across political, economic, and sociocultural factors-Namqom, Formosa, Argentina, and New Haven, Connecticut, United States. We collected infant urine, maternal urine, and human milk samples from mother-infant dyads in Formosa (n = 13) and New Haven (n = 21). We used untargeted liquid chromatography with high-resolution mass spectrometry (LC-HRMS) to annotate environmental contaminants and endogenous metabolites in these samples, and we analyzed the data using exposome-wide association studies (EWAS) followed by pathway enrichment. We found statistically significant differences between the chemical exposure profiles of the Argentinian and US mothers, mostly involving pesticides; however, we observed similarities in the infant urine and human milk environmental contaminant profiles, suggesting that the maternal body may buffer infant exposure through human milk. We also found that infants and mothers were exposed to contaminants that were associated with alterations in amino acid and carbohydrate metabolism. Infants additionally showed alterations in vitamin metabolism, including vitamins B1, B3, and B6. Differences in chemical exposure profiles may be related to structural factors. Despite variation in the composition of exposure profiles between the two study sites, environmental contaminant exposure was associated with similar patterns in human physiology when we considered contaminants comprehensively rather than individually, with implications for metabolic and cardiovascular disease risk as well as infant cognitive development.

Maternal adiponectin restores cholinergic vasodilation in resistance vessels from adult offspring exposed to maternal obesity in utero.

Maternal obesity increases the risk of cardiovascular and metabolic disease in the offspring both during childhood and adult life. Pregnant women and mice with obesity have lower circulating levels of adiponectin (ADN) compared to lean controls. ADN is an adipokine involved in regulating energy metabolism, vascular function, and placental function. We hypothesized that offspring of obese mice have impaired resistance artery function, which can be prevented by restoration of normal circulating ADN levels in obese dams during late pregnancy. Adult female mice were fed either control or obesogenic diet and mated with control diet-fed males. Control dams received a continuous infusion of phosphate saline buffer (PBS) during late pregnancy whereas obese females received either PBS or ADN. After weaning, offspring were fed a control diet. Mesenteric arteries (MsA) were dissected from adult offspring and mounted in a wire myograph or fixed for histology. MsA responses to vasoconstrictors (phenylephrine and endothelin-1) were not different between infusion groups. However, the vasodilatory responses to acetylcholine were reduced in offspring from obese dams as compared to control-fed dams. ADN supplementation during pregnancy restored the cholinergic vasodilatory responses of resistance vessels in offspring from obese dams. These observations suggest a target during obese pregnancy for the prevention of the long-lasting vascular effects in the offspring.

The role of dietary inflammatory index in metabolic diseases: the associations, mechanisms, and treatments.

In recent years, the prevalence of metabolic diseases has increased significantly, posing a serious threat to global health. Chronic low-grade inflammation is implicated in the development of most metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and cardiovascular disease, serving as a link between diet and these conditions. Increasing attention has been directly toward dietary inflammatory patterns that may prevent or ameliorate metabolic diseases. The Dietary Inflammatory Index (DII) was developed to assess the inflammatory potential of dietary intake. Consequently, a growing body of research has examined the associations between the DII and the risk of several metabolic diseases. In this review, we explore the current scientific literature on the relationships between the DII, T2DM, obesity, and dyslipidemia. It summarizes recent findings and explore potential underlying mechanisms from two aspects: the interaction between diet and inflammation, and the link between inflammation and metabolic diseases. Furthermore, this review discusses the therapeutic strategies, including dietary modifications, prebiotics, and probiotics, and discusses the application of the DII in metabolic diseases, as well as future research directions.

Higher Adherence to the Mediterranean Diet Is Associated with a Lower Risk of Steatotic, Alcohol-Related, and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Analysis

Background and Aims: Metabolic liver disease is associated with obesity, insulin resistance, cardiovascular disease, and metabolic disorders. A Mediterranean diet (MD), known for its anti-inflammatory and antioxidant properties, is effective in managing various chronic diseases, including liver diseases. This study aimed to explore the influence of adherence to the MD on the risk of chronic metabolic diseases, including steatotic liver disease (SLD), metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-related liver diseases (ALDs). Methods: This retrospective cohort study analyzed 5395 individuals from a single center between 2020 and 2022, grouped by adherence to the MD using the Korean Mediterranean Diet Adherence Score (K-MEDAS). MASLD score, ALD, and cardiovascular risk factors were also assessed. Statistical analyses were performed using 1:1 exact matching and multiple regression to compare the less adherent (K-MEDAS 0–7) and highly adherent (K-MEDAS 8–13) groups. Results: Adjusting for confounding variables, high adherence to the MD was significantly associated with lower rates of SLD (odds ratio [OR] 0.818, 95% confidence interval [CI] 0.700–0.957, p = 0.012), MASLD (OR 0.839, 95% CI 0.714–0.986, p = 0.033), and ALD (OR 0.677, 95% CI 0.671–0.683, p &lt; 0.001). Post-propensity score matching analysis revealed that the highly adherent group exhibited significantly lower triglyceride levels, triglyceride and glucose index, atherogenic Index of Plasma, and Framingham risk scores than the less adherent group. Conclusions: Good adherence to the MD considerably reduces the risk of SLD, MASLD, and ALD, underscoring its protective effects and potential to prevent metabolic liver diseases and their complications.

Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study.

(1) Background: Interleukin 17 (IL17) and toll-like receptor 4 (TLR4) elevate the risk of metabolic and liver diseases. (2) Methods: This study's objective was to explore the association of IL17 and TLR4 gene polymorphisms with MASLD susceptibility and test their effect on serum IL17 and TLR4 levels. A total of 43 patients with MASLD (MASH/MAFL) and 38 healthy individuals were genotyped for IL17F-A7488G, IL17A-G197A, TLR4-Asp299Gly, and TLR4-Thr399Ile polymorphisms using PCR-RFLP. ELISA methods determined IL17F, IL17A, and TLR4 serum levels. (3) Conclusions: Patients carrying the variant genotypes (A/G + G/G) of IL17-A7448G (OR = 5.25), (G/A + A/A) of IL17-G197A (OR = 10.57), (Asp/Gly + Gly/Gly) of TLR4-Asp299Gly (OR = 3.52), or (Thr/Ile + Ile/Ile) of TLR4-Thr399Ile (OR = 9.87) had significantly increased odds of MASH. Genotype (G/A + A/A) of IL17-G197A was significantly associated with the odds of MAFL (p = 0.0166). Allele A of the IL17-G197A polymorphism was significantly related to increased odds of MAFL (OR = 4.13, p = 0.0133). In contrast, allele A of IL17-G197A (OR = 5.41, p = 0.008), allele Gly of TLR4-Asp299Gly (OR = 3.19, p = 0.046), and allele Ile of TLR4-Thr399Ile (OR = 6.94, p = 0.008) polymorphisms were significantly related to an increased risk of MASH. Allele A of IL17A-G197A, allele Gly of TLR4-Asp299Gly, and allele Ile of TLR4-Thr399Ile gene polymorphisms were significantly associated with the increased odds of MASLD. In patients with MASLD, we found significant influence from the IL17A-G197A gene polymorphism on IL17F levels (p = 0.0343).

Correction for Kwan et al., "Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes".

Correction for Kwan et al., "Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes".

Maternal Broccoli Powder Intake Ameliorates Insulin Resistance and Inflammation via AMPK/mTOR Pathway in the Livers of High-Fructose-Fed Male Rat Offspring Exposed to Maternal Protein Restriction.

Sub-optimal prenatal conditions such as maternal undernutrition during pregnancy and lactation posit high risks of adult metabolic diseases. High fructose intake causes insulin resistance and liver inflammation contributing to metabolic diseases. However, food-based preventive measure for these metabolic diseases in the offspring is under-researched. This study aims to investigate the effect of maternal broccoli powder (BP) intake during lactation on insulin resistance and liver inflammation in high-fructose-diet-fed adult male offspring exposed to maternal protein restriction. Pregnant Wistar rats are provided normal protein (NP) or low protein (LP) diets and 0% or 0.74% BP-containing NP diets and 0% or 0.74% BP-containing LP diet during lactation. At weaning, offspring receiving water (W) or 10% fructose solution (Fr) are assigned into six groups: NP/NP/W, NP/NP/Fr, NP/NPBP/Fr, LP/LP/W, LP/LP/Fr, and LP/LPBP/Fr. At week 13, plasma insulin, macrophage infiltration, activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) phosphorylation, and autophagy flux markers are examined. LP/LPBP/Fr shows lower insulin levels and Homeostatic model assessment for insulin resistance (HOMA-IR) values than LP/LP/Fr. Liver macrophage infiltration are decreased in LP/LPBP/Fr. LP/LPBP/Fr exhibits upregulated AMPK phosphorylation, downregulated mTOR phosphorylation, and increased Microtubule-associated protein1A/1B-light chain 3B-II (LC3B-II) levels. Maternal BP intake during lactation ameliorates insulin resistance and inflammation in the livers of adult offspring on a high-fructose diet from LP mothers.

Actions of thyroid hormones and thyromimetics on the liver.

Thyroid hormones (triiodothyronine and thyroxine) are pivotal for metabolic balance in the liver and entire body. Dysregulation of the hypothalamus-pituitary-thyroid axis can contribute to hepatic metabolic disturbances, affecting lipid metabolism, glucose regulation and protein synthesis. In addition, reductions in circulating and intrahepatic thyroid hormone concentrations increase the risk of metabolic dysfunction-associated steatotic liver disease by inducing lipotoxicity, inflammation and fibrosis. Amelioration of hepatic metabolic disease by thyroid hormones in preclinical and clinical studies has spurred the development of thyromimetics that target THRB (the predominant thyroid hormone receptor isoform in the liver) and/or the liver itself to provide more selective activation of hepatic thyroid hormone-regulated metabolic pathways while reducing thyrotoxic side effects in tissues that predominantly express THRA such as the heart and bone. Resmetirom, a liver and THRB-selective thyromimetic, recently became the first FDA-approved drug for metabolic dysfunction-associated steatohepatitis (MASH). Thus, a better understanding of the metabolic actions of thyroid hormones and thyromimetics in the liver is timely and clinically relevant. Here, we describe the roles of thyroid hormones in normal liver function and pathogenesis of MASH, as well as some potential clinical issues that might arise when treating patients with MASH with thyroid hormone supplementation or thyromimetics.

Maternal Diet during Pregnancy Alters the Metabolites in Relation to Metabolic and Neurodegenerative Diseases in Young Adult Offspring

Maternal nutrition during the critical period of pregnancy increases the susceptibility of offspring to the development of diseases later in life. This study aimed to analyze metabolite profiles to investigate the effect of maternal diet during pregnancy on changes in offspring plasma metabolites and to identify correlations with metabolic parameters. Pregnant Sprague-Dawley rats were exposed to under- and overnutrition compared to controls, and their offspring were fed a standard diet after birth. Plasma metabolism was profiled in offspring at 16 weeks of age using liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS). We analyzed 80 metabolites to identify distinct metabolites and metabolic and neurodegenerative disease-associated metabolites that were sex-differentially altered in each group compared to controls (p &lt; 0.05, VIP score &gt; 1.0). Specifically, changes in 3-indolepropionic acid, anthranilic acid, linoleic acid, and arachidonic acid, which are involved in tryptophan and linoleic acid metabolism, were observed in male offspring and correlated with plasma leptin levels in male offspring. Our results suggest that fatty acids involved in tryptophan and linoleic acid metabolism, which are altered by the maternal diet during pregnancy, may lead to an increased risk of metabolic and neurodegenerative diseases in the early life of male offspring.

Role of Akkermansia muciniphila in insulin resistance.

Insulin resistance (IR) is a pathogenic factor in numerous metabolic diseases. The gut microbiota plays a crucial role in maintaining the function of the intestinal barrier and overall human health, thereby influencing IR. Dysbiosis of the gut microbiota can contribute to the development of IR. Therefore, it is essential to maintain a balanced and diverse gut microbiota for optimal health. Akkermansia muciniphila, a widely present microorganism in the human intestine, has been shown to regulate gastrointestinal mucosal barrier integrity, reduce endotoxin penetration, decrease systemic inflammation levels, and improve insulin sensitivity. Reduced abundance of A.muciniphila is associated with an increased risk of IR and other metabolic diseases, highlighting its correlation with IR. Understanding the role and regulatory mechanism of A.muciniphila is crucial for comprehending IR pathogenesis and developing novel strategies for preventing and treating related metabolic disorders. Individual variations may exist in both the gut microbiota composition and its impact on IR among different individuals. Further investigation into individual differences between A.muciniphila and IR will facilitate advancements in personalized medicine by promoting tailored interventions based on the gut microbiota composition, which is a potential future direction that would optimize insulin sensitivity while preventing metabolic disease occurrence. In this review, we describe the physiological characteristics of A.muciniphila, emphasize its roles in underlying mechanisms contributing to IR pathology, and summarize how alterations in its abundance affect IR development, thereby providing valuable insights for further research on A.muciniphila, as well as new drug development targeting diabetes.