Risk Factor For Metabolic Diseases Research Articles

Oral combined contraceptives induce liver mitochondrial reactive oxygen species and whole-body metabolic adaptations in female mice.

Compared to age-matched men, pre-menopausal women show greater resilience against cardiovascular disease (CVD), hepatic steatosis, diabetes and obesity - findings that are widely attributed to oestrogen. However, meta-analysis data suggest that current use of oral combined contraceptives (OC) is a risk factor for myocardial infarction, and OC use further compounds with metabolic disease risk factors to increase CVD susceptibility. While mitochondrial function in tissues such as the liver and skeletal muscle is an emerging mechanism by which oestrogen may confer its protection, effects of OC use on mitochondria and metabolism in the context of disease risk remain unexplored. To answer this question, female C57Bl/6J mice were fed a high fat diet and treated with vehicle or OCs for 3, 12 or 20weeks (n=6 to 12 per group) at a dose and ratio that mimic the human condition of cycle cessation in the low oestrogen, high progesterone stage. Liver and skeletal muscle mitochondrial function (respiratory capacity, H2 O2 , coupling) was measured along with clinical outcomes of cardiometabolic disease such as obesity, glucose tolerance, hepatic steatosis and aortic atherosclerosis. The main findings indicate that regardless of treatment duration, OCs robustly increase hepatic mitochondrial H2 O2 levels, likely due to diminished antioxidant capacity, but have no impact on muscle mitochondrial H2 O2 . Furthermore, OC-treated mice had lower adiposity and hepatic triglyceride content compared to control mice despite reduced wheel running, spontaneous physical activity and total energy expenditure. Together, these studies describe tissue-specific effects of OC use on mitochondria as well as variable impacts on markers of metabolic disease susceptibility. KEY POINTS: Oestrogen loss in women increases risk for cardiometabolic diseases, a link that has been partially attributed to negative impacts on mitochondria and energy metabolism. To study the effect of oral combined contraceptives (OCs) on hepatic and skeletal muscle mitochondria and whole-body energy metabolism, we used an animal model of OCs which mimics the human condition of cessation of hormonal cycling in the low oestrogen, high progesterone state. OC-treated mice have increased hepatic mitochondrial oxidative stress and decreased physical activity and energy expenditure, despite displaying lower adiposity and liver fat at this time point. These pre-clinical data reveal tissue-specific effects of OCs that likely underlie the clinical findings of increased cardiometabolic disease in women who use OCs compared to non-users, when matched for obesity.

Age-specific prevalence, subtypes and risk factors of metabolic diseases in Chinese adults and the different patterns from other racial/ethnic populations

BackgroundAge has substantial influence on metabolic diseases patterns. Ethnic disparities of metabolic characteristics between Chinese and other populations also exist. Large-scale investigations of age-specific prevalence, subtypes and modifiable risk factors of metabolic disorders are essential to promote individualized strategies for the control and prevention of metabolic diseases in multi-ethnic populations. The study aims to address the age-specific prevalence, subtype characteristics and risk factor profiles of metabolic diseases among different races/ethnicities.MethodsWe analyzed data from the China Noncommunicable Disease Surveillance 2010 and the National Health and Nutrition Evaluation Survey (NHANES). We examined the prevalence and subtypes of hypertension, diabetes and hyperlipidemia across age groups in four ethnic populations. We also investigated the odds ratios (ORs) of metabolic diseases associated with 11 classical risk factors in the young and the elder Mainland Chinese.ResultsThe sex and BMI standardized prevalence of hypertension in Chinese aged 18–40 years was 18.5% and was the highest among the four populations. The main pathophysiologic subtype of diabetes was characterized by insulin resistance, instead of β-cell dysfunction in Mainland Chinese, and this pattern was more evident in obese subjects. The major subtype of hyperlipidemia in Mainland Chinese was hypertriglyceridemia, while Non-Hispanic Whites and Blacks were more prone to high low-density lipoprotein cholesterol. For risk of hypertension, diabetes and hyperlipidemia, young Chinese adults were more prone to general and central obesity than older ones. The other factors showed similar effects on the young and the old.ConclusionsThe age-specific prevalence, subtypes and risk factors of metabolic diseases were substantially different in Chinese and other ethnic/racial populations.

Dietary Acid Load Associated with Hypertension and Diabetes in the Elderly.

Diet can affect the body's acid-base balance due to its content of acid or base precursors. There is conflicting evidence for the role of metabolic acidosis in the development of cardiometabolic disorders, hypertension (HT), and insulin resistance (IR). We hypothesized that dietary acid load (DAL) is associated with adverse metabolic risk factors and aimed to investigate this in the elderly. A total of 114 elderly participants were included in the study. The participants were divided into four groups, such as HT, diabetes (DM), both HT and DM, and healthy controls. Anthropometric, biochemical, and clinical findings were recorded. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) results were obtained for three days, 24-hour dietary records via a nutrient database program (BeBiS software program). The groups were matched for age, gender, and BMI. There was a statistically significant difference between the groups regarding NEAP (p =0.01) and no significant difference for PRAL ( p = 0.086). The lowest NEAP and PRAL levels were seen in the control group while the highest in the HT group. Both NEAP and PRAL were correlated with waist circumference (r = 0,325, p = 0.001; r=0,231, p =0,016, respectively). Our data confirmed that subjects with HT and DM had diets with greater acid-forming potential. High NEAP may be a risk factor for chronic metabolic diseases, particularly HT. PRAL could not be shown as a significantly different marker in all participants. Dietary content has a significant contribution to the reduction of cardiovascular risk factors, such as HT, DM, and obesity.

Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes.

The association between serum osteocalcin (OCN) levels and metabolic dysfunction-associated fatty liver disease (MAFLD) is still controversial. Moreover, few studies have explored their relationship in type 2 diabetes mellitus (T2DM) patients so far. The present study aimed to investigate the association of serum OCN levels with MAFLD in Chinese T2DM patients. This cross-sectional, real-world study included 1889 Chinese T2DM inpatients. MAFLD was diagnosed by abdominal ultrasonography. Participants were divided into four groups according to serum OCN quartiles, among which the clinical characteristics were compared. The association of serum OCN levels with the presence of MAFLD was also analyzed in subjects. After controlling for sex, age, and diabetes duration, the prevalence of MAFLD significantly decreased across the serum OCN quartiles (55.3%, 52.0%, 48.6%, and 42.1% for the first, second, third, and fourth quartiles, respectively, P < 0.001 for trend). A fully adjusted multiple logistic regression analysis showed that serum OCN levels were independently and negatively associated with the presence of MAFLD in T2DM patients (odds ratio, 0.832; 95% confidence interval, 0.719-0.962; P = 0.013). Furthermore, there were significant decreases in HOMA-IR (P = 0.001 for trend) and C-reactive protein (P < 0.001 for trend) levels across the serum OCN quartiles after controlling for sex, age, and diabetes duration. Serum OCN levels were independently and negatively associated with the presence of MAFLD in Chinese T2DM patients, partially due to the improvement of insulin resistance and inflammation mediated by OCN. Serum OCN may be used as a biomarker to assess the risk of MAFLD in T2DM patients.

Profound Sensitivity of the Liver to the Direct Effect of Insulin Allows Peripheral Insulin Delivery to Normalize Hepatic but Not Muscle Glucose Uptake in the Healthy Dog.

Endogenous insulin secretion is a key regulator of postprandial hepatic glucose metabolism, but this process is dysregulated in diabetes. Subcutaneous insulin delivery alters normal insulin distribution, causing relative hepatic insulin deficiency and peripheral hyperinsulinemia, a major risk factor for metabolic disease. Our aim was to determine whether insulin's direct effect on the liver is preeminent even when insulin is given into a peripheral vein. Postprandial-like conditions were created (hyperinsulinemia, hyperglycemia, and a positive portal vein to arterial glucose gradient) in healthy dogs. Peripheral (leg vein) insulin infusion elevated arterial and hepatic levels 8.0-fold and 2.8-fold, respectively. In one group, insulin's full effects were allowed. In another, insulin's indirect hepatic effects were blocked with the infusion of triglyceride, glucagon, and inhibitors of brain insulin action (intracerebroventricular) to prevent decreases in plasma free fatty acids and glucagon, while blocking increased hypothalamic insulin signaling. Despite peripheral insulin delivery the liver retained its full ability to store glucose, even when insulin's peripheral effects were blocked, whereas muscle glucose uptake markedly increased, creating an aberrant distribution of glucose disposal between liver and muscle. Thus, the healthy liver's striking sensitivity to direct insulin action can overcome the effect of relative hepatic insulin deficiency, whereas excess insulin in the periphery produces metabolic abnormalities in nonhepatic tissues.

An overview of the negative effects of obesity on the body and its improvement through diet

Obesity is a major risk factor for chronic metabolic diseases and is strongly associated with premature death. The mechanisms linking obesity to the body's metabolic disorders include dyslipidemia, hyperglycemia, hyperinsulinemia, and hypertension. In addition, several recent studies have suggested that six types of diets (including low calorie, low carbohydrate, low fat, and high protein diets, plant-based diet, and low carbohydrate ketogenic diet) could significantly affect weight change, with each diet having its advantages and disadvantages.

The Sexual Dimorphism of Human Adipose Depots.

The amount and the distribution of body fat exhibit trajectories that are sex- and human species-specific and both are determinants for health. The enhanced accumulation of fat in the truncal part of the body as a risk factor for cardiovascular and metabolic diseases is well supported by epidemiological studies. In addition, a possible independent protective role of the gluteofemoral fat compartment and of the brown adipose tissue is emerging. The present narrative review summarizes the current knowledge on sexual dimorphism in fat depot amount and repartition and consequences on cardiometabolic and reproductive health. The drivers of the sex differences and fat depot repartition, considered to be the results of complex interactions between sex determination pathways determined by the sex chromosome composition, genetic variability, sex hormones and the environment, are discussed. Finally, the inter- and intra-depot heterogeneity in adipocytes and progenitors, emphasized recently by unbiased large-scale approaches, is highlighted.

Effect of traditional fat replacement by oleogel made of beeswax and canola oil on processed meat (steak type) quality

Oleogel (OG) has become an alternative fat ingredient for many foods as well as meat and its related meat products due to its health beneficial effects. The objective of this study was to characterize the processed meat properties as well as analyse the trends of consumer acceptability of meat products by using OG utilization as a fat replacer. Processed meat samples were prepared for 3 groups including i) processed meat (only red part) without any additive addition: control, ii) 50% beef tallow adding: BT, and iii) 50% OG, obtained from beeswax and canola oil mixture, substituting of BT: OG. All meat samples determined the physical, physicochemical, and lipid profiles as well as sensorial properties. The results found that OG treatment showed desirable physical and physicochemical characteristics. The soft texture of the meat sample was observed in the OG group when compared with other treatments. Furthermore, OG replacing the traditional fat in processed meat has significantly reduced the percentage of total saturated fatty acid (SFA, 68.37±2.19) and increased the total unsaturated fatty acid (USFA, 31.63±1.63) (p &lt; 0.05) when compared with BT group treatment (SFA: 79.52±3.72 and USFA: 20.48±0.31). OG treatment also showed improvement in processed meat through the significantly higher score of overall liking from the consumer evaluation (p &lt; 0.05). The results of this study could be used as preliminary results for the development of healthy meat model products, contributing to driving meat consumption together with the reduction of risk factors of metabolic diseases.

Functional Complementation of Anti-Adipogenic Phytonutrients for Obesity Prevention and Management.

Obesity is an established risk factor for metabolic disease. This study explores the functional complementation of anti-adipogenic phytonutrients for obesity prevention and management. Nine phytonutrients were selected based on their ability to affect the expression of one or more selected adipogenic biomarker proteins. The phytonutrients include berberine, luteolin, resveratrol, fisetin, quercetin, fucoidan, epigallocatechin gallate, hesperidin, and curcumin. The selected adipogenic biomarker proteins include PPARɣ, SREBP1c, FASN, PLIN1, FABP4, and β-catenin. Individually, phytonutrients had variable effects on the expression level of selected adipogenic biomarker proteins. Collectively, the functional complementation of nine phytonutrients suppressed de novo fatty acid biosynthesis via the negative regulation of PPARɣ, FASN, PLIN1, and FABP4 expression; activated glycolysis via the positive regulation of SREBP1c expression; and preserved cell–cell adhesion via the inhibition of β-catenin degradation. In primary human subcutaneous preadipocytes, the composition of nine phytonutrients had more potent and longer lasting anti-adipogenic effects compared to individual phytonutrients. In a diet-induced obesity murine model, the composition of nine phytonutrients improved glucose tolerance and reduced weight gain, liver steatosis, visceral adiposity, circulating triglycerides, low-density lipoprotein cholesterol, and inflammatory cytokines and chemokines. The functional complementation of anti-adipogenic phytonutrients provides an effective approach toward engineering novel therapeutics for the prevention and management of obesity and metabolic syndrome.

Extracellular matrix remodeling facilitates obesity-associated cancer progression.

Obesity, a global public health concern, is an important risk factor for metabolic diseases and several cancers. Fibro-inflammation in adipose tissues (ATs) is tightly associated with the pathologies of obesity; excessive or uncontrolled extracellular matrix (ECM) production in AT has a crucial role in this pathogenesis. The ECM is a critical and functional component of various tissues, providing a mechanical and chemical network of proteins that controls cell survival, development, and tissue repair. The ECM is tightly regulated and dynamically remodeled; this is an important factor for AT expansion and can result in modifications to the physical shape and biological function of AT. Here, we focus on ECM remodeling in AT and how it affects obesity-related cancer progression.

Cross-sectional study of passive opiate smoking in relation to stroke and some of stroke attributable risk factors in women

Opiate use is related to neuropathological disorders, stroke and stroke attributable risk factors. However, secondary exposure to opiate in relation to the above-mentioned complications is studied only in animal models and remains to be evaluated in human populations. We tested whether passive exposure to opiate is associated with stroke and the known stroke predictive factors. We carried out a cross-sectional study of 1541 never smoker women who participated in the Rafsanjan Cohort Study (RCS) with their husbands (2015–2017 recruitment phase). RCS is one of the 19 geographic districts of the Prospective Epidemiological Research Studies in Iran (PERSIAN cohort study). Unadjusted and adjusted multiple logistic regression analyses were performed to evaluate the relationship between second-hand opiate exposure (husband opiate smoking after marriage) and the odds ratio of stroke and the following stroke risk factors and predictive parameters: overweight/obesity (BMI > 25), cholesterol (chol) > 200 mg/dl, fasting blood sugar (FBS) > 125 mg/dl, low density lipoprotein (LDL) > 100 mg/dl, triglyceride (TG) > = 150 mg/dl, hypertension, diabetes, and chronic headache. We observed a significant increased adjusted odds ratio (OR) of stroke (OR = 3.43, 95% CI:1.33–8.82) and its risk factors LDL > 100 mg/dl (OR = 1.37, 95% CI:1.01–1.87) and FBS > 125 mg/dl (OR = 1.58, 95% CI:1.08–2.30) in women associated with husbands’ opiate smoking. This relationship was observed after adjusting for the confounding parameters including age, education years, and first-degree family history of the relevant diseases. The increased odds ratio for stroke and high LDL displayed a dose-sensitive trend with years of husband’s opiate smoking after marriage (respective p-trends: 0.02 & 0.01). We did not observe a significant association between passive opiate smoking and high TG, high Chol or the diseases diabetes, hypertension and chronic headache. However, 89% increased odds ratio of chronic headache was observed to be associated with passive opiate smoking for more than 10 years (OR = 1.89, 95% CI:1.02–3.50). We found an increased risk of stroke and high LDL and FBS in women associated with passive opiate smoking. Furthermore, a dose-sensitive connection was found between the risks of stroke, high LDL and chronic headache with the years of passive opiate exposure. Our results point to the necessity of the future analyses, which further assess whether passive opiate exposure could be considered as an independent risk factor for stroke and metabolic diseases.

Medical and social aspects of health security in the formation of public health

Introduction. Monitoring of the health status of the population as a whole, assessment and analysis of the leading determinants of health, including genetic, behavioral, anthropogenic, biophysiological factors, represent one of the global functions of public health, focused on health protection and provision of medical services. To date, health disorders are primarily related to lifestyle and are always a collection of individual personalized health data. Unhealthy diet and low physical activity are risk factors for the development of a number of chronic non-communicable diseases, primarily cardiovascular, metabolic, in particular type 2 diabetes mellitus and some types of cancer. These risk factors lead to early disability, a decrease in the quality and life expectancy of people, disability, as well as the health budget and the economy. So, if on average only 3 % of the health budget is spent on disease prevention programs, then about 7 % of the budget in the EU countries is spent on the treatment of obesity and turns into 2.8 % of world GDP. In this regard, the implementation of early preventive measures is characterized by favorable and positive results.&#x0D; Purpose. Analyzes the role of unhealthy diet and low physical activity as key risk factors for cardiovascular and metabolic diseases, especially in the population of patients with type 2 diabetes mellitus.&#x0D; Methods and materials. The characteristics of the presented studies included in the article cover international experience and analysis of the pilot study conducted on a population sample of patients with type 2 diabetes mellitus. To assess the economic costs associated with unhealthy diet and low physical activity, a general approach was used based on the analysis of individual diseases, in particular, type 2 diabetes mellitus, using population attributive fractions, regression method.&#x0D; Results. Based on the data obtained, it follows that patients with an unhealthy diet and low physical activity, burdened with overweight or obesity, have a high five-year risk of developing new cases of type 2 diabetes and cardiovascular complications. This includes early disability and the economic costs of providing medical care. Using the example of a number of European countries and its own results, this study is focused on assessing the economic damage that is associated with unhealthy diet and low physical activity among the population, regardless of the region of residence and the metropolis.

Macrophages, Chronic Inflammation, and Insulin Resistance.

The prevalence of obesity has reached alarming levels, which is considered a major risk factor for several metabolic diseases, including type 2 diabetes (T2D), non-alcoholic fatty liver, atherosclerosis, and ischemic cardiovascular disease. Obesity-induced chronic, low-grade inflammation may lead to insulin resistance, and it is well-recognized that macrophages play a major role in such inflammation. In the current review, the molecular mechanisms underlying macrophages, low-grade tissue inflammation, insulin resistance, and T2D are described. Also, the role of macrophages in obesity-induced insulin resistance is presented, and therapeutic drugs and recent advances targeting macrophages for the treatment of T2D are introduced.

Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation both in vitro and in vivo

ABSTRACT High blood glucose is one of the risk factors for metabolic disease and INS (insulin) is the key regulatory hormone for glucose homeostasis. Hypoinsulinemia accompanied with hyperglycemia was diagnosed in mice with pancreatic β-cells exhibiting autophagy deficiency; however, the underlying mechanism remains elusive. The role of secretory autophagy in the regulation of metabolic syndrome is gaining more attention. Our data demonstrated that increased macroautophagic/autophagic activity leads to induction of insulin secretion in β-cells both in vivo and in vitro under high-glucose conditions. Moreover, proteomic analysis of purified autophagosomes from β-cells identified a group of vesicular transport proteins participating in insulin secretion, implying that secretory autophagy regulates insulin exocytosis. RAB37, a small GTPase, regulates vesicle biogenesis, trafficking, and cargo release. We demonstrated that the active form of RAB37 increased MAP1LC3/LC3 lipidation (LC3-II) and is essential for the promotion of insulin secretion by autophagy, but these phenomena were not observed in rab37 knockout (rab37 -/- ) cells and mice. Unbalanced insulin and glucose concentration in the blood was improved by manipulating autophagic activity using a novel autophagy inducer niclosamide (an antihelminthic drug) in a high-fat diet (HFD)-obesity mouse model. In summary, we reveal that secretory autophagy promotes RAB37-mediated insulin secretion to maintain the homeostasis of insulin and glucose both in vitro and in vivo.

The association between ambient temperature exposure during infancy and overweight at age two years

BACKGROUND AND AIM: Childhood overweight and obesity is increasing in prevalence globally and is a risk factor for metabolic disease in adulthood. We have previously described an association between exposure to higher ambient temperatures during infancy and rapid infant weight gain. We aimed to examine the association between ambient temperature exposure during the first year of life and overweight at age two years. METHODS: A population-based cohort study using data from the Israeli network of public maternal and child health clinics from 2011 to 2018. The study population was restricted to children born with birthweight &amp;#x2265;2500g (N=579,404). We assessed exposure to ambient temperature using a high-resolution spatio-temporal model and calculated the average annual exposure during the first year of life for each infant based on daily temperature at their address. Overweight at two years was defined as &amp;#x3e;85th percentile in World Health Organization age and sex-adjusted body mass index. We calculated relative risks using log-linear models and fitted general additive models with thin plate regression splines while adjusting for sub-district, neighbourhood socio-economic index, ethnicity, month and year of birth and average ambient temperature during pregnancy. RESULTS: We found a positive association between ambient temperature exposure and risk of overweight at age two years. Children exposed to the highest temperature quintile (&amp;#x2265;22.0&amp;#xb0;C) had an adjusted relative risk of 1.16 (95% CI 1.12, 1.19) compared to those exposed to the lowest quintile (&amp;#x3c;19.6&amp;#xb0;C). Modelling temperature as a continuous variable using general additive models showed an increase in risk with higher temperature exposure up to approximately 23&amp;#xb0;C when the risk levelled out. CONCLUSIONS: Exposure to higher ambient temperatures during infancy is associated with increased risk of overweight at age two years in Israel. Future studies should explore this association in other populations and examine possible biological mechanisms. KEYWORDS: temperature, child health, climate

The associations between fasting glucose, lipids and uric acid levels strengthen with the decile of uric acid increase and differ by sex

Background and aimSerum lipids, glucose and uric acid are well-known risk factors for metabolic syndrome and cardiovascular diseases; however, how serum uric acid levels are associated with fasting glucose and lipid levels remains to be evaluated. Methods and resultsA cross-sectional study was performed in 104,328 males and 74,916 females. Quantile regression analyses were adopted to optimally fit the associations between levels of uric acid, lipids and glucose. Fasting high-density lipoprotein cholesterol (HDL-C) levels were negatively associated with serum uric acid levels; the associations remained stable in males but strengthened in females with increasing uric acid concentrations. Non-HDL-C and triglyceride (TG) levels were positively associated with serum uric acid levels; the associations also strengthened across deciles of uric acid levels from low to high. Fasting glucose levels were positively associated with uric acid levels in both sexes except in males in the 1st and 2nd deciles of uric acid concentrations; the association coefficients for females were higher than coefficients in males in each decile of uric acid levels. All associations had distinguishable patterns by sex except non-HDL-C, which was associated with uric acid levels with relatively similar trends between sexes. Adjustment for known confounding factors only slightly altered the above associations. ConclusionsFasting serum uric acid levels are associated with fasting levels of HDL-C, non-HDL-C, TG and glucose; the associations strengthened with the deciles of uric acid increase and displayed non-negligible sex differences.

Worst spasticity in patients post-stroke associated with MNSOD ALA16VAL polymorphism and interleukin-1β

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1β, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1β levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.

Sedentary behavior and the risk of stroke: A systematic review and dose-response meta-analysis

Background and aimsThe sedentary behavior in people's daily life has continued to increase in recent years, causing many studies to focus on its relationship with diseases. Several studies have shown that sedentary behavior is an independent risk factor for cardiovascular disease and metabolic disease. Therefore, we performed a meta-analysis to assess the association between sedentary behavior and the risk of stroke. Methods and resultsTwo independent investigators searched for prospective cohort studies on the association between sedentary behavior and stroke risk, published before February 2022. We pooled adjusted effect size and performed the dose-response analysis by random-effect model. Seven studies with 677,614 participants and 15,135 stroke events during a median follow-up of 12.2 years were included. The pooled hazard ratio (HR) of stroke was 1.16 (95% confidence interval [CI]: 1.09–1.24) with no significant heterogeneity (I2 = 0.0%, p for heterogeneity = 0.983). In dose-response analysis, a nonlinear association between sedentary behavior and stroke risk was discovered. Stroke risk began to increase when sedentary time exceeded 3.7 h/d (HR, 1.01; 95% CI, 0.97–1.05). And when reached 11 h/d, a significantly increased risk of stroke was observed (HR, 1.21; 95% CI 1.12–1.31). ConclusionA nonlinear association was found in the dose-response analysis, with increased risk only when sedentary time exceeded a certain level. Further research is needed to explain the biological mechanisms by which sedentary time above a certain threshold significantly increases stroke risk. (PROSPERO registration number: CRD42022311544)

Swertiamarin ameliorates diet-induced obesity by promoting adipose tissue browning and oxidative metabolism in preexisting obese mice.

Obesity is a risk factor for many metabolic diseases. Efficient therapeutic strategies are urgently needed. Swertiamarin (STM) prevents obesity and the associated insulin resistance and inflammation. However, the therapeutic effects of STM on preexisting obesity remain unclear. Therefore, in this study we aim to investigate the effects of STM on energy expenditure and fat browning in mice with preexisting obesity. C57BL/6J mice are fed with a high-fat diet (HFD) for 8 weeks to induce obesity and then gavaged (or not) with STM for 10 weeks. The whole-body energy metabolism of mice is examined by indirect calorimetry. The results show that after 10 weeks of treatment, STM markedly prevents HFD-induced weight gain, chronic inflammation, insulin resistance, and hepatic steatosis. STM promotes oxygen consumption and energy expenditure. The level of uncoupling protein 1 is enhanced in the brown and white adipose tissues of STM-treated mice. STM increases the phosphorylation of AMP-activated protein kinase and the expressions of genes involved in fat oxidation, reducing fat deposition in skeletal muscles. Meanwhile, STM does not affect the intestinal microbiotic composition. Overall, STM supplementation may serve as a potential therapy for obesity.

Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease and leading cause of cardiovascular diseases. The progression of AS is a multi-step process leading to high morbidity and mortality. Hyperglycemia, dyslipidemia, advanced glycation end products (AGEs), inflammation and insulin resistance which strictly involved in diabetes are closely related to the pathogenesis of AS. A growing number of studies have linked AGEs to AS. As one of the risk factors of cardiac metabolic diseases, dysfunction of VSMCs plays an important role in AS pathogenesis. AGEs are increased in diabetes, participate in the occurrence and progression of AS through multiple molecular mechanisms of vascular cell injury. As the main functional cells of vascular, vascular smooth muscle cells (VSMCs) play different roles in each stage of atherosclerotic lesions. The interaction between AGEs and receptor for AGEs (RAGE) accelerates AS by affecting the proliferation and migration of VSMCs. In addition, increasing researches have reported that AGEs promote osteogenic transformation and macrophage-like transformation of VSMCs, and affect the progression of AS through other aspects such as autophagy and cell cycle. In this review, we summarize the effect of AGEs on VSMCs in atherosclerotic plaque development and progression. We also discuss the AGEs that link AS and diabetes mellitus, including oxidative stress, inflammation, RAGE ligands, small noncoding RNAs.