Development Of Metabolic Syndrome Research Articles

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric liver disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by the accumulation of lipid species in hepatocytes, leading to liver inflammation that can progress to steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing to NAFLD encompass genetic variations and metabolic disorders such as obesity, diabetes, and insulin resistance. Moreover, transgenerational influences, resulting in an imbalance of gut microbial composition, epigenetic modifications, and dysregulated hepatic immune responses in offspring, play a pivotal role in pediatric NAFLD development. Maternal nutrition shapes the profile of microbiota-derived metabolites in offspring, exerting significant influence on immune system regulation and the development of metabolic syndrome in offspring. In this review, we summarize recent evidence elucidating the intricate interplay between gut microbiota, epigenetics, and immunity in fetuses exposed to maternal nutrition, and its impact on the onset of NAFLD in offspring. Furthermore, potential therapeutic strategies targeting this network are also discussed.

Abstract PO4-19-12: Trial in progress: An Observational Study to Examine Changes in Metabolic Syndrome Components in Patients With Breast Cancer Receiving (Neo)Adjuvant Aromatase Inhibitors

Abstract Background: (Neo) adjuvant systemic therapy has been shown to adversely impact metabolic health manifested as weight gain, dyslipidemia, and insulin resistance, which ultimately lead to the development of metabolic syndrome (MetS). MetS increases the risk of development for type 2 diabetes mellitus and cardiovascular disease and is associated with an increased risk of breast cancer recurrence, death due to breast cancer, and all-cause mortality. We have previously reported that 76% of metabolically healthy women receiving (neo) adjuvant chemotherapy will develop MetS at a median of 15 weeks. The impact of aromatase inhibitors (AIs) on metabolic health has not been systematically assessed in a longitudinal study. We hypothesize that AIs in the (neo) adjuvant setting will alter metabolic parameters and have embarked on a clinical trial to study this. Methods: This is a prospective observational study that will include: postmenopausal patients with newly diagnosed, early-stage hormone receptor (HR)-positive breast cancer with planned (neo)adjuvant treatment with an AI. Participants will be excluded if they have received or have planned treatment with (neo)adjuvant chemotherapy or are currently receiving antidiabetic medications or cholesterol-lowering agents. All patients will undergo a baseline assessment that includes: BMI, physical exam inclusive of blood pressure, waist circumference, assessment of body fat, lipid profile, insulin, metabolic biomarkers, and completion of the Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES). Following institution of an AI, reassessment of the aforementioned tests will be repeated after 4 months and 12 months of therapy. The primary endpoint is the change in insulin resistance (as measured by HOMA-IR, homeostatic model assessment for insulin resistance) at 4 months. Secondary endpoints include the change in HOMA-IR at 12 months and the change in individual MetS components, metabolic biomarkers, anthropometric measurements, as well as FACT-ES scores from baseline to 4- and 12-months of AI treatment. The mean paired differences will be calculated for HOMA-IR measurements as well as for the secondary endpoints, and the 1-sided paired t-test will be used to test for statistical significance. One-way analysis of covariance will be used to compare means while adjusting for age, race/ethnicity, and BMI. Using a 1-sided paired t-test for the mean difference in HOMA-IR measurements from baseline to 4 months, we will have 80% power to detect an effect size of 0.405 with 40 patients (α = 0.05). Enrollment began in April 2023 and is ongoing. Contact alevee@coh.org for more information. Given the increased recognition of the importance of metabolic health in breast cancer outcomes, this data will inform future trials that focus on maintaining metabolic health in breast cancer survivors. Citation Format: Alexis LeVee, Nora Ruel, Victoria Seewaldt, Joanne Mortimer. Trial in progress: An Observational Study to Examine Changes in Metabolic Syndrome Components in Patients With Breast Cancer Receiving (Neo)Adjuvant Aromatase Inhibitors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-12.

Ameliorative effect of bofutsushosan (Fangfengtongshengsan) extract on the progression of aging-induced obesity.

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.

Patients with Celiac Disease Have High Prevalence of Fatty Liver and Metabolic Syndrome.

In recent years, patients with celiac disease (CeD) have been reported to have a high prevalence of fatty liver and metabolic syndrome. We conducted a systematic review and meta-analysis to assess the prevalence of fatty liver and metabolic syndrome in patients with CeD and effect of gluten-free diet in them. The PubMed, Embase and the Cochrane Library databases were searched for original studies upto November 18, 2022. We included full-text articles published in the English language after 1990 that used well-defined criteria for CeD, fatty liver and metabolic syndrome. A random effects model was used to calculate pooled prevalence. Of 350 studies identified, 11 studies (n = 2578) were included in the analysis. On analysis of both cross-sectional and longitudinal studies, pooled prevalence of fatty liver and metabolic syndrome in treatment-naïve patients with CeD were 18.2% (95% CI 8.3-30.8%, n = 1237) and 4.3% (95% CI 2.4-6.7, n = 1239) and in those on GFD of varying duration was 28.2% (95% CI 20.7-36.4%, n = 1368) and 21.3% (95% CI 11.7-32.9%, n = 2193), respectively. There was no difference in the prevalence of fatty liver and metabolic syndrome between low- or high-income group countries. Patients with CeD have a high prevalence of fatty liver and metabolic syndrome which increases further with the initiation of GFD. Patients with CeD should thus be screened and monitored for development of fatty liver and metabolic syndrome. They should be counselled appropriately regarding their diet and inclusion of physical activity in their lifestyle.

ARTERIAL HYPERTENSION AS A COMPONENT OF METABOLIC SYNDROME IN MEN IN AN OPEN URBAN POPULATION

Purpose. To determine blood pressure (BP) levels and the prevalence of arterial hypertension (AH), as a component of metabolic syndrome, in men of an open urban population aged 25–64 years. Materials and methods. A one-time epidemiological study was conducted on a representative sample of men 25–64 years old, formed from the electoral lists of citizens of the city of Tyumen in the amount of 1000 people, the response was 85.0%. To analyze the prevalence of AH as a component of the metabolic syndrome, the NCEP ATP III (2004), IDF (2005), All-Russian Scientific Society of Cardiology (2009) assessment criteria were used. Results. The levels of systolic BP in men of the Tyumen population were high due to the average age groups of 35–44 and 45–54 years; in the same groups there was a significant increase in the average values and percentile distribution of the trait. According to the levels of diastolic BP in men of the Tyumen population, a directional age trend of the indicator was formed with a significant increase in its levels in each subsequent age group. In terms of the prevalence of AH, the standardized indicator in the male population of Tyumen 25–64 years old was 59.8%; a positive relationship was established with age in the younger and older age categories. Conclusion. Thus, the study results obtained in an open urban population, which identified the most vulnerable age categories of men with regard to the development of metabolic syndrome, represent a scientific basis for the formation of a preventive program in the region.

Male LEW.1WR1 Rats Develop Metabolic Dysfunction, Steatohepatitis, and Liver Damage

Most patients with non-alcoholic steatohepatitis (NASH) have insulin resistance, and there is a near-universal association between NASH and insulin resistance. Insulin resistance induces lipid accumulation in the liver, leading to the development of metabolic syndrome. However, most NASH rodent models fail to develop metabolic syndrome. LEW.1WR1 rats that are 23 weeks old showed increased body mass, epididymal fat, and liver mass, suggesting obesity-driven metabolic dysfunction. We have characterized steatosis, inflammation, Mallory–Denk body formation with hematoxylin and eosin (H&E), and fibrosis with Trichome blue staining. The presence of hepatic fibrosis with other features of NASH described above is one of the major strengths of this model since most of the currently available NASH models do not develop microvesicular steatosis or fibrosis. Together with the other important features of NASH described above, we confirm that male LEW.1WR1 rats develop NASH and insulin resistance with a standard diet.

Gut microbiota – a new link in the pathogenesis of osteoarthritis (literature review)

The intestinal microbiota (IMB) can indirectly affect the course of ostearthritis (OA) at the systemic level by stimulating a chronic nonspecific inflammatory reaction in the synovial membrane and subchondral bone, the cause of which is an increase in the amount of circulating lipopolysaccharides (LPS) of the bacterial wall, as well as provoke the development of metabolic syndrome, which links the two necessary components of the pathogenesis of OA. The result of direct exposure is the formation of leaky gut syndrome with the activation of LPS of the bacterial wall of mild inflammation, provoking the production of proinflammatory cytokines, the effect of which on synoviocytes and chondrocytes leads to their activation with subsequent production of IL-6 and IL-8, which contributes to the persistence of inflammation. By correlation analysis, the relationship of three taxa with OA joint damage was proved, namely, the order Desulfovibrionales and the genus Ruminiclostridium 5 – with knee joint OA, Methanobacteriaceae – with knee joint OA, and OA of any localization, and the appearance and degree of contamination with the genus Streptococcus correlated with the severity of pain syndrome. The metabolic syndrome itself can provoke the development of dysbiosis, so it can also be its consequence. A change in the composition of the microbiota in the form of the predominance of the genus Clostridium and the species Staphylococcus aureus with a decrease in the diversity of microorganisms is associated with an increase in the amount of adipose tissue in the body, dyslipidemia, insulin resistance with impaired carbohydrate metabolism. Low levels of LPS in the blood are found in obese patients even in the absence of an obvious focus of infection due to violations in the CMB, they signal TLR-4, triggering systemic inflammation. Studies have shown a positive effect of prescribing proand prebiotics on the course of OA, which makes IMB a promising target for the treatment and prevention of OA.

Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Age changes in the lipid profile of rats against experimental metabolic syndrome

Background. Metabolic syndrome (MS) is characterized by the development of pathogenetic mechanisms that potentiate abdominal obesity and insulin resistance. Obesity is a stimulator of the synthesis of active components of adipose tissue – adipocytes (AT), which leads to numerous metabolic and hemodynamic disorders. The study of pathophysiological mechanisms based on the basis of morphometric and biochemical parameters of blood pressure, taking into account age and gender aspects, is of great topical importance. Purpose – of the study is to identify differences in the morphological and histological parameters of adipocytes against the background of the development of metabolic syndrome in animals of different ages and sexes. Materials and Methods. To achieve the goal, an experimental study was conducted on 108 white rats of the WAG/G Sto population. Each age group consisted of a control (36) and an experimental series (72), where the animals were divided by sex. The 1st group included young immature 3-month-old rats of the control (1K) and experimental (1A) subgroups. Group 2 consisted of 36 sexually mature rats aged 5–6 months, divided into 2 subgroups: control (2K) and experimental (2A). The third group consisted of 36 old rats aged 18 months, divided into the control 3K (12) subgroup (6 old females and 6 old males), and the experimental subgroup 3A – of 12 females and 12 males. Results. The hypodermic tissue of all experimental groups consists of adipocytes, the size, shape and density of which had age and gender differences. In group 1A of both subgroups, the cells had a round and oval shape and were significantly smaller in size compared to groups 2A and 3A. Adipocytes of rats have morphological changes against the background of experimental modeling of MS in taking into account age and gender aspects. It was established that in the group of old animals, hypertrophic processes prevail in BP, against the background of greatly reduced hyperplastic processes. Analyzing and comparing the size of adipose tissue cells between experimental groups 1A, 2A and 3A, the dependence of the increase in the size of adipocytes, which is related to the age of the animal, was noted. Conclusions. Experimental changes in the integrative indicators of AT of rats in the pathogenesis of MS are related to age and sex. An inversely proportional dependence of the decrease in the resistance of adipocytes as the age of the animal increases was noted. The obtained results can be designated as a biological marker that determines the development of obesity against the background of disorders of the systemic inflammatory response and insulin resistance.

Adipocines and longevity: connections and paradoxes

Adipose tissue is an active endocrine organ that regulates energy homeostasis throughout the body by releasing hundreds of biologically active substances called adipokines. Dysregulation of adipokines is a key feature of insulin resistance with the development of metabolic syndrome and type 2 diabetes mellitus, which is an age-dependent pathology. In turn, dysregulation of adipokines and insulin resistance are associated with the development of metabolic deficiency and senile asthenia syndrome in older age groups. Previous studies have shown that the absence of insulin resistance and low prevalence of diabetes among centenarians are metabolic prerequisites for increased lifespan, suggesting a possible role for adipokine homeostasis in healthy longevity. Among numerous adipokines, adiponectin is considered a protective factor, showing a negative correlation with major metabolic disorders associated with age and obesity, and a positive association with life expectancy and insulin sensitivity among centenarians. Despite all the apparent protective effects of adiponectin, large-scale epidemiological studies have revealed the opposite aspect of adiponectin as a predictor of all-cause mortality and cardiovascular disease in patients with heart failure as well as kidney disease. In this review, the clinical significance of adiponectin is considered in centenarians from the point of view of the development of the main geriatric syndrome - senile asthenia, as well as cardiovascular risk and mortality.

EFFECT OF AMMONIUM PYRROLIDINEDITHIOCARBAMATE ON THE DEVELOPMENT OF OXIDATIVE STRESS IN BICEPS FEMORIS MUSCLES OF RATS DURING MODELLED METABOLIC SYNDROME

Excessive consumption of high-calorie food, a sedentary lifestyle and increased psycho-emotional stress are risk factors for the development of metabolic syndrome. These factors are especially relevant for residents of countries with highly developed economies. Metabolic syndrome is accompanied not only by metabolic disorders, but also leads to the development of a systemic inflammatory response, which is associated with excessive production and circulation of cytokines in the blood. As a rule, the activation of the transcription factor NF-κB leads to an increase in the production of pro-inflammatory cytokines.&#x0D; The aim of this work is to determine the effect of the NF-κB transcription factor activation inhibitor on the activity of antioxidant enzymes, the production of superoxide anion radical, the content of oxidatively modified proteins, and the concentration of malondialdehyde in the biceps femoris muscle of rats who underwent experimental metabolic syndrome.&#x0D; The study included 24 sexually mature male Wistar rats weighing 200-260 g. The animals were divided into 4 groups of 6 animals each. The first group was the control group; the second group involved the rats exposed to metabolic syndrome simulated by adding a 20% fructose solution as the only source of drinking water to the standard vivarium diet for 60 days; the third group involved the animals received ammonium pyrrolidine dithiocarbamate in a dose of 76 mg/kg intraperitoneally 3 times a week for 60 days; the fourth group was exposed to the combined effect of the ammonium pyrrolidinedithiocarbamate administration during modeled metabolic syndrome. In this study we investigated a 10% homogenate of the biceps femoris muscle with the research focus on several parameters: superoxide anion radical production, superoxide dismutase and catalase activity, malondialdehyde concentration, and the presence of oxidatively modified proteins.&#x0D; Simulation of the metabolic syndrome led to the development of oxidative stress in the biceps muscle of rats that was accompanied by an increase in the production of the superoxide anion radical and a decrease in the activity of antioxidant enzymes. The administration of ammonium pyrrolidinedithiocarbamate during modeled metabolic syndrome caused a decrease in the basic production of superoxide anion radical, production of superoxide anion radical by the microsomal electron transport chain and production of superoxide anion radical by the mitochondrial electron transport chain by 30.28%, 26.21 %, and 27.00%, respectively, compared to the rats in metabolic syndrome group. Superoxide dismutase activity increased by 78.81% and catalase activity grew by 144.74% compared to the metabolic syndrome group. The concentration of free malondialdehyde under the administration of ammonium pyrrolidinedithiocarbamate during metabolic syndrome reduced by 51.80%, and the content of oxidatively modified proteins decreased by 31.74% compared to the metabolic syndrome group.&#x0D; The administration of ammonium pyrrolidinedithiocarbamate, an NF-κB transcription factor activation inhibitor, effectively prevents the development of oxidative stress in the biceps femoris muscle of rats with modeled metabolic syndrome.&#x0D; This study is a part of the initiative research project No. 0124U000092 "High- and low-intensity phenotypes of systemic inflammatory response: molecular mechanisms and new medical technologies for their prevention and correction".

The regulatory role of m6A methylation modification in metabolic syndrome pathogenesis and progression.

Metabolic syndromes are characterized by various complications caused by disrupted glucose and lipid metabolism, which are major factors affecting the health of a population. However, existing diagnostic and treatment strategies have limitations, such as the lack of early diagnostic and therapeutic approaches, variability in patient responses to treatment, and cost-effectiveness. Therefore, developing alternative solutions for metabolic syndromes is crucial. N6-methyladenosine (m6A) is one of the most abundant modifications that determine the fate of RNA. m6A modifications are closely associated with metabolic syndrome development and present novel prospects for clinical applications. Aberrant m6A modifications have been detected during inflammatory infiltration, apoptosis, autophagy, iron sagging, necrosis, and scorching during metabolic syndrome pathogenesis and progression. However, few reviews have systematically described the correlation between m6A modifications and these factors concerning metabolic syndrome pathogenesis and progression. This study summarizes the m6A methylation regulators and their roles in metabolic syndrome development, highlighting the potential of m6A modification as a biomarker in metabolic disorders.

Resistin in patients with psoriasis vulgaris during PUVA therapy

BACKGROUND: Currently, psoriasis represents a serious medical and social problem, and it is one of the most common chronic skin diseases. Over the past decades, special attention has been paid to the association of psoriasis with various diseases, such as cardiovascular diseases, inflammatory bowel diseases, depression, etc. Common comorbidities of psoriasis include metabolic syndrome or obesity. Resistin is one of the hormones produced by adipose tissue, the concentration of which increases markedly in patients with psoriasis. Resistin expression is induced by proinflammatory cytokines such as IL-1, IL-6, IL-12 and TNF-a. In turn, an increase in resistin levels leads to increased production of pro-inflammatory cytokines involved in the development of psoriasis, thereby promoting the recruitment of leukocytes during the inflammatory process leading to chronic inflammation. Taken together, the above changes may contribute to the development of metabolic syndrome in psoriasis. Among the effective methods of treating the disease, phototherapy methods (PUVA and UVB 311 nm) remain relevant. Considering these data, it is of interest to study the level of resistin in the serum of patients with psoriasis and its change after a course of PUVA.&#x0D; AIM: The aim of our study was to evaluate the serum resistin level in patients with psoriasis vulgaris before and after PUVA.&#x0D; MATERIALS AND METHODS: The study was conducted at the department of Skin and Venereology diseases at the Sechenov University in the period from June 2022 to November 2023. The study included 30 patients with psoriasis vulgaris of moderate severity (PASI 20), of whom there were 16 men and 14 women. The healthy control group included 20 participants (11 men and 9 women). All patients had blood drawn from a vein during hospitalization and after a course of PUVA. Healthy participants underwent a single blood draw from a vein.&#x0D; RESULTS: A noticeable decrease in the level of resistin in the blood serum was revealed after a course of PUVA in all patients with psoriasis compared to baseline values. In addition, after treatment, resistin levels approached the values recorded in healthy participants.&#x0D; CONCLUSION: Thus, our study allows us to consider resistin as a biological marker of the effectiveness of PUVA in the treatment of patients with psoriasis vulgaris, as well as a predictor of the occurrence of concomitant diseases in patients with psoriasis.

Mapping the knowledge structure of research on insulin resistance and metabolic syndrome: a global perspective

BackgroundInsulin resistance is a major pathogenic factor that plays a crucial role in the development of metabolic syndrome and has been proposed as one of its underlying causes. Most diagnostic criteria for metabolic syndrome do not directly include insulin resistance. Furthermore, research on insulin resistance continues to provide information on the development and treatment of metabolic syndromes and related health conditions. Therefore, this bibliometric analysis aimed to investigate the current research status and identify possible future research hotspots in the area of metabolic syndrome and insulin resistance by analyzing Scopus-based studies.MethodsTo collect published data on metabolic syndrome and insulin resistance, this study used the Scopus database as its data source without a particular starting date but including records up to December 31, 2022. The gathered documents were then exported to VOSviewer v.1.6.18 to analyze and visualize country collaborations and identify research areas of high interest.ResultsThe study presents an overview of 1932 records between 1988 and 2022, focusing on metabolic syndrome and insulin resistance. Of these records, 77.33% were original journal articles, while 13.30% were review articles. Additionally, 9.35% of the documents fall under other types of publication, including letters, notes, and editorials. The United States came out on top with 463 items, accounting for 23.96% of the contributions in this field, followed by Japan in second place with 119 items (6.16%). China (n = 113, 5.85%) and the United Kingdom (n = 113, 5.85%) ranked third. Most publications on metabolic syndrome and insulin resistance focus on key terms related to the pathogenesis of insulin resistance syndrome, the use of waist circumference as a crucial clinical indicator to evaluate the risk of metabolic syndrome, and the association between metabolic syndrome and oxidative stress and a pro-inflammatory state.ConclusionsThis study presents the first bibliometric analysis of publications focusing on metabolic syndrome and insulin resistance. The findings of this study offer a comprehensive global perspective on the research carried out on metabolic syndrome and insulin resistance and can be an invaluable source for future research.

Prediction of metabolic syndrome following a first pregnancy

The prevalence of metabolic syndrome is rapidly increasing in the United States. We hypothesized that prediction models using data obtained during pregnancy can accurately predict the future development of metabolic syndrome. This study aimed to develop machine learning models to predict the development of metabolic syndrome using factors ascertained in nulliparous pregnant individuals. This was a secondary analysis of a prospective cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study [nuMoM2b-HHS]). Data were collected from October 2010 to October 2020, and analyzed from July 2023 to October 2023. Participants had in-person visits 2 to 7 years after their first delivery. The primary outcome was metabolic syndrome, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, which was measured within 2 to 7 years after delivery. A total of 127 variables that were obtained during pregnancy were evaluated. The data set was randomly split into a training set (70%) and a test set (30%). We developed a random forest model and a lasso regression model using variables obtained during pregnancy. We compared the area under the receiver operating characteristic curve for both models. Using the model with the better area under the receiver operating characteristic curve, we developed models that included fewer variables based on SHAP (SHapley Additive exPlanations) values and compared them with the original model. The final model chosen would have fewer variables and noninferior areas under the receiver operating characteristic curve. A total of 4225 individuals met the inclusion criteria; the mean (standard deviation) age was 27.0 (5.6) years. Of these, 754 (17.8%) developed metabolic syndrome. The area under the receiver operating characteristic curve of the random forest model was 0.878 (95% confidence interval, 0.846-0.909), which was higher than the 0.850 of the lasso model (95% confidence interval, 0.811-0.888; P<.001). Therefore, random forest models using fewer variables were developed. The random forest model with the top 3 variables (high-density lipoprotein, insulin, and high-sensitivity C-reactive protein) was chosen as the final model because it had the area under the receiver operating characteristic curve of 0.867 (95% confidence interval, 0.839-0.895), which was not inferior to the original model (P=.08). The area under the receiver operating characteristic curve of the final model in the test set was 0.847 (95% confidence interval, 0.821-0.873). An online application of the final model was developed (https://kawakita.shinyapps.io/metabolic/). We developed a model that can accurately predict the development of metabolic syndrome in 2 to 7 years after delivery.

The role of 27-hydroxycholesterol in meta-inflammation.

27-Hydroxycholesterol (27OHChol), a prominent cholesterol metabolite present in the bloodstream and peripheral tissues, is a kind of immune oxysterol that elicits immune response. Recent research indicates the involvement of 27OHChol in metabolic inflammation (meta-inflammation) characterized by chronic responses associated with metabolic irregularities. 27OHChol activates monocytic cells such that they secrete pro-inflammatory cytokines and chemokines, and increase the expression of cell surface molecules such as pattern-recognition receptors that play key roles in immune cell-cell communication and sensing metabolism-associated danger signals. Levels of 27OHChol increase when cholesterol metabolism is disrupted, and the resulting inflammatory responses can contribute to the development and complications of metabolic syndrome, including obesity, insulin resistance, and cardiovascular diseases. Since 27OHChol can induce chronic immune response by activating monocyte-macrophage lineage cells that play a crucial role in meta-inflammation, it is essential to understand the 27OHChol-induced inflammatory responses to unravel the roles and mechanisms of action of this cholesterol metabolite in chronic metabolic disorders.

Sipyimigwanjung-tang, a traditional herbal medication, alleviates weight gain in a high-fat diet-induced obese mice model

Obesity leads to the development of metabolic syndrome and comorbidities. Overweight and obesity continue to be a relentless global issue. Sipyimigwanjung-tang (SGT), a traditional herbal medication, was first mentioned in Dongui Sasang Shinpyun and has been used to treat edema, meteorism, and jaundice, which are common findings associated with obesity. The main physiological feature of obesity is expanded adipose tissue, which causes several impairments in liver metabolism. Therefore, this study aimed to investigate the anti-obesity effects of SGT in the epididymal white adipose tissue (eWAT) and livers of high-fat diet (HFD)-induced obese mice. SGT significantly blocked HFD-induced weight gain in C57BL/6N mice. In addition, SGT effectively reduced the increased weight and adipocyte size in eWAT of HFD-induced obese C57BL/6 N mice. Moreover, SGT significantly decreased the elevated gene expression of Peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and Sterol regulatory element-binding protein 1 in the eWAT of HFD-induced obese mice. Furthermore, SGT significantly decreased lipid accumulation in the livers of HFD-induced obese mice and differentiated 3T3-L1 adipocytes. Hence, the present study provides substantial evidence that SGT has potential therapeutic effects on obesity.

Physical activity in metabolic syndrome.

Obesity has become one of the global epidemics, contributing to the burden of disease in society, increasing the risk of diabetes, cardiovascular and liver diseases. Inadequate energy balance resulting from excessive energy intake and insufficient physical activity (PA) is one of the main factors contributing to the incidence of obesity and the development of metabolic syndrome (MetS). Treatment options for obesity include lifestyle modifications, pharmacotherapy and bariatric surgery, with the latter being the most effective treatment. Lifestyle interventions involving increased PA and reduced caloric intake improve metabolic outcomes. Early implementation of exercise leads to improved physical fitness, better glycemic control and lipid profile. Undertaking systematic PA is associated with better quality of life, improves insulin sensitivity, causes additional weight loss, reduces its adverse effects on bone mass and results in better body composition. In this narrative review we summarized the current state of knowledge on the impact of PA on the components of MetS and the latest recommendations for PA in patients with MetS.

Maternal Obesity Modulates Cord Blood Concentrations of Proprotein Convertase Subtilisin/Kexin-type 9 Levels.

In utero exposure to maternal obesity or diabetes is considered a pro-inflammatory state. To evaluate whether cord blood proprotein convertase subtilisin/kexin-type 9 (PCSK9), which is regulated by inflammation and metabolic derangements, is elevated in neonates born to overweight, obese, or diabetic mothers. A retrospective study in full-term neonates born between 2010 and 2023, at Brigham and Women's Hospital. There were 116 neonates included in our study, of which 74 (64%) were born to overweight/obese mothers and 42 (36%) were born to nonoverweight/nonobese mothers. Neonates born to overweight/obese mothers had significantly higher cord blood concentrations of PCSK9 compared with neonates born to nonoverweight/nonobese group (323 [253-442] ng/mL compared with 270 [244-382] ng/mL, P = .041). We found no significant difference in cord blood concentrations of PCSK9 between neonates of diabetic mothers compared with neonates of nondiabetic mothers. In multivariate linear regression analysis, higher cord plasma PCSK9 concentration was significantly associated with maternal overweight/obesity status (b = 50.12; 95% CI, 4.02-96.22; P = .033), after adjusting for gestational age, birth weight, male sex, and intrauterine growth restriction. Neonates born to mothers with overweight/obesity have higher cord blood PCSK9 concentrations compared with the nonoverweight/nonobese group, and higher cord blood PCSK9 concentrations were significantly associated with maternal overweight/obesity status, after adjusting for perinatal factors. Larger longitudinal studies are needed to examine the role of PCSK9 in the development of metabolic syndrome in high-risk neonates born to overweight, obese, or diabetic mothers.

Genetic deletion of hormone-sensitive lipase in mice reduces cerebral blood flow but does not aggravate the impact of diet-induced obesity on memory.

Hormone-sensitive lipase (HSL) is active throughout the brain and its genetic ablation impacts brain function. Its activity in the brain was proposed to regulate bioactive lipid availability, namely eicosanoids that are inflammatory mediators and regulate cerebral blood flow (CBF). We aimed at testing whether HSL deletion increases susceptibility to neuroinflammation and impaired brain perfusion upon diet-induced obesity. HSL-/-, HSL+/-, and HSL+/+ mice of either sex were fed high-fat diet (HFD) or control diet for 8 weeks, and then assessed in behavior tests (object recognition, open field, and elevated plus maze), metabolic tests (insulin and glucose tolerance tests and indirect calorimetry in metabolic cages), and CBF determination by arterial spin labeling (ASL) magnetic resonance imaging (MRI). Immunofluorescence microscopy was used to determine coverage of blood vessels, and morphology of astrocytes and microglia in brain slices. HSL deletion reduced CBF, most prominently in cortex and hippocampus, while HFD feeding only lowered CBF in the hippocampus of wild-type mice. CBF was positively correlated with lectin-stained vessel density. HSL deletion did not exacerbate HFD-induced microgliosis in the hippocampus and hypothalamus. HSL-/- mice showed preserved memory performance when compared to wild-type mice, and HSL deletion did not significantly aggravate HFD-induced memory impairment in object recognition tests. In contrast, HSL deletion conferred protection against HFD-induced obesity, glucose intolerance, and insulin resistance. Altogether, this study points to distinct roles of HSL in periphery and brain during diet-induced obesity. While HSL-/- mice were protected against metabolic syndrome development, HSL deletion reduced brain perfusion without leading to aggravated HFD-induced neuroinflammation and memory dysfunction.