BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

OBJECTIVES: To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome (MS). METHODS: Forty Wistar rats were randomly divided into normal control group (n=8) and 3 phlegm syndrome model groups (induced by high-fat, high-sugar, and high-salt feeding and a single-dose intraperitoneal STZ injection; n=24) treated with daily gavage of saline, Wendan Decoction (3.6 g/kg), or metformin (0.1 g/kg) for 4 weeks. General conditions and glucose and lipid metabolism parameters of the rats were monitored, and serum LPS, liver histopathology, hepatic expressions of FXR, CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined. Gut microbiota structure was analyzed using 16S rDNA sequencing, and serum bile acids were quantified with UHPLC-MS/MS. RESULTS: The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis, increased body weight, abdominal circumference, Lee's index, FBG, FINS, HOMA-IR, TG, TC, LDL and LPS, and decreased HDL level. The abundance of Bacteroidetes, Megamonas, and Bacteroides in gut microbiota increased while Firmicutes, Lachnospiraceae_NK4A136_group, isohyodeoxycholic acid, and glycohyodeoxycholic acid decreased significantly; hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models. Treatment with Wendan Decoction effectively alleviated hepatic pathology, reduced body weight and abdominal circumference, improved glucose and lipid metabolic profiles and gut microbiota structure, and reversed the changes in hepatic and ileal protein expressions. Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes, Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid. CONCLUSIONS Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.
Animals ; Gastrointestinal Microbiome/drug effects* ; Metabolic Syndrome/microbiology* ; Bile Acids and Salts/metabolism* ; Rats, Wistar ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Male ; Fibroblast Growth Factors/metabolism* ; Liver/metabolism* ; Cholesterol 7-alpha-Hydroxylase/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism*

OBJECTIVES: To study the relationship between skeletal muscle mass index (SMI) and metabolic phenotypes of obesity in adolescents, and to provide a basis for the prevention and control of adolescent obesity and related metabolic diseases. METHODS: A total of 1 352 adolescents aged 12 to 18 years were randomly selected by stratified cluster sampling in Yinchuan City from October 2017 to September 2020, and they were surveyed using questionnaires, physical measurements, body composition measurements, and laboratory tests. According to the diagnostic criteria for metabolic abnormalities and the definition of obesity based on the body mass index, the subjects were divided into four metabolic phenotypes: metabolically healthy normal weight, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity. The association between SMI and the metabolic phenotypes was analyzed using multivariate logistic regression. RESULTS: The SMI level in the metabolically unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity groups was lower than that in the metabolically healthy normal weight group (P<0.001). Multivariate logistic regression analysis showed that after adjusting for gender and age, a higher SMI level was a protective factors for adolescents to develop metabolic unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity phenotypes (OR=0.74, 0.60, and 0.54, respectively; P<0.001). CONCLUSIONS Increasing SMI can reduce the risk of the development of metabolic unhealthy/obesity.
Adolescent ; Humans ; Body Mass Index ; Metabolic Syndrome/metabolism* ; Muscle, Skeletal/metabolism* ; Obesity, Metabolically Benign/diagnosis* ; Pediatric Obesity ; Phenotype ; Risk Factors ; Child

Objective: To explore abdominal fat mass distribution and contents among obese children via magnetic resonance imaging (MRI), and analyze the correlations of abdominal adipose tissue with anthropometric and metabolic parameters. Methods: Cross-sectional study. There were 60 obese children admitted to the Children's Health Care Department and Endocrinology Department at Children's Hospital of Nanjing Medical University from July 2016 to December 2018. Children's gender, age, height, weight, body composition, waist circumference and blood pressure were recorded. The levels of fasting blood glucose, lipids, insulin were measured, and liver ultrasound was performed, and the body mass index Z score (BMI-Z), waist-to-height ratio (WHtR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. In addition, contents of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) were calculated according to feedback of abdominal MRI scan images. The associations between the contents of abdominal adipose tissue, physical examination status and metabolic disorders among obese children were analyzed through correlation analysis and regression analysis. Receiver operating characteristic (ROC) curve was used to compare the accuracy of fat mass in different parts of the abdomen in predicting their metabolic disorders. Results: A total of 60 children were enrolled in the study, included 44 boys and 16 girls, with age of (9.2±1.4) years. The contents of SAT, VAT and TAAT among the 60 children were positively associated with BMI-Z (r=0.60, 0.46, 0.59), body fat percentage (r=0.64, 0.67, 0.68) and waist-to-height ratio (r=0.60, 0.57, 0.61) (all P<0.01). Meanwhile, contents of SAT and TAAT were also positively correlated with systolic blood pressure (r=0.47, 0.49), triglyceride (r=0.33, 0.35) and HOMA-IR (r=0.33, 0.28)(all P<0.05). In order to adjust the confounding effects among various variables, regression analysis was applied and the result showed that the body fat percentage (β=0.59, 0.66, 0.65) and waist-to-height ratio (β=0.53, 0.63, 0.59) were most related to abdominal fat contents (all P<0.01), including SAT, VAT and TAAT among obese children. According to ROC, SAT had outstanding evaluation performances for the diagnosis of insulin resistance and metabolic syndrome, while VAT had excellent evaluation performances for non-alcoholic fatty liver disease (area under curve=0.68, 0.69, 0.69, 95%CI 0.54-0.82, 0.55-0.84, 0.53-0.85, P=0.017, 0.014, 0.019). Conclusions: As one of the best indexes, body fat percentage and WHtR can be used to predict the contents of SAT, VAT and TAAT among obese children. With the increase of abdominal SAT or VAT, the risks for insulin resistance, metabolic syndrome and non-alcoholic fatty liver disease would increase. Assessment of abdominal fat and metabolic risks in obese children should combine BMI-Z with waist circumference and body composition analysis.
Abdominal Fat/metabolism* ; Body Mass Index ; Child ; Cross-Sectional Studies ; Female ; Humans ; Insulin Resistance ; Magnetic Resonance Imaging ; Male ; Metabolic Diseases/metabolism* ; Metabolic Syndrome/metabolism* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/metabolism*

Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 10 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.
Animals ; Bacteria ; classification ; genetics ; isolation & purification ; metabolism ; Butyrates ; metabolism ; Fatty Liver ; drug therapy ; Fungal Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; genetics ; Hyperglycemia ; drug therapy ; Hyperlipidemias ; drug therapy ; Intestines ; drug effects ; microbiology ; Male ; Metabolic Syndrome ; drug therapy ; Mice ; Mice, Obese ; Prebiotics ; Wolfiporia ; chemistry

Over the past decade, there has been increasing attention on the interaction between microbiota and bile acid metabolism. Bile acids are not only involved in the metabolism of nutrients, but are also important in signal transduction for the regulation of host physiological activities. Microbial-regulated bile acid metabolism has been proven to affect many diseases, but there have not been many studies of disease regulation by microbial receptor signaling pathways. This review considers findings of recent research on the core roles of farnesoid X receptor (FXR), G protein-coupled bile acid receptor (TGR5), and vitamin D receptor (VDR) signaling pathways in microbial-host interactions in health and disease. Studying the relationship between these pathways can help us understand the pathogenesis of human diseases, and lead to new solutions for their treatments.
Bile Acids and Salts/metabolism* ; Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism* ; Metabolic Syndrome/metabolism* ; Receptors, Calcitriol/physiology* ; Receptors, Cytoplasmic and Nuclear/physiology* ; Receptors, G-Protein-Coupled/physiology* ; Signal Transduction/physiology*

Taurine is an abundant, β-amino acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.
Acidosis, Lactic ; Arthritis ; Brain Diseases ; Calcium ; Cardiovascular System ; Central Nervous System ; Cytoprotection ; Energy Metabolism ; Gene Expression ; Heart Failure ; Japan ; MELAS Syndrome ; Metabolic Diseases ; Mitochondrial Diseases ; Neurodegenerative Diseases ; Pathology ; Quality Control ; Taurine*

BACKGROUNDTranscription factor 7-like 2 (TCF7L2)-rs7903146 polymorphism is associated with increased risk of type 2 diabetes. The response of insulin and insulin resistance to artichoke leaf extract (ALE) may be affected by TCF7L2-rs7903146 polymorphism.

OBJECTIVEThis study examined the effects of ALE supplementation on metabolic parameters of the TCF7L2-rs7903146 polymorphism in patients with metabolic syndrome (MetS).

DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONSThis double-blind clinical trial was conducted on 80 patients with MetS in Sina Clinic, Khoy, Iran. The patients were randomized into ALE or placebo groups to receive either ALE (1800 mg/d as four tablets) or matching placebo for 12 weeks.

MAIN OUTCOME MEASURESAnthropometric indices, blood pressure, glucose and lipid profile levels were measured before and after the study. Moreover, patients were genotyped for TCF7L2 polymorphism.

RESULTSALE supplementation decreased insulin level and the homeostasis model assessment of insulin resistance (HOMA-IR) in patients with the TT genotype of TCF7L2-rs7903146 polymorphism (P < 0.05). There was no significant interaction between blood pressure, glucose and lipid profile response to ALE supplementation.

CONCLUSIONThe responses of insulin and HOMA-IR to ALE supplementation have shown an interaction with single-nucleotide polymorphism rs7903146 in TCF7L2.

TRIAL REGISTRATIONIranian Registry of Clinical Trial IRCT201409033320N9.

Adult ; Blood Glucose ; metabolism ; Cynara scolymus ; Dietary Supplements ; Double-Blind Method ; Female ; Genotype ; Humans ; Insulin ; blood ; Insulin Resistance ; genetics ; Male ; Metabolic Syndrome ; blood ; drug therapy ; genetics ; Middle Aged ; Phytotherapy ; Plant Extracts ; pharmacology ; Polymorphism, Single Nucleotide ; Transcription Factor 7-Like 2 Protein ; genetics

Brown adipose tissue (BAT) plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue (WAT), have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BATactivation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.
Adipose Tissue, Brown ; metabolism ; Aging ; metabolism ; Animals ; Cachexia ; metabolism ; pathology ; Disease Models, Animal ; Energy Metabolism ; Humans ; Metabolic Syndrome ; metabolism ; Neoplasms ; metabolism ; pathology ; Obesity ; metabolism ; Thermogenesis

OBJECTIVEAssessment of the comprehensive relationship among apolipoprotein CIII (apoCIII) levels, inflammation, and metabolic disorders is rare.

METHODSA total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCIII in the association of inflammation with metabolic syndrome (MetS).

RESULTSPatients with MetS showed higher levels of apoCIII [95.1 (73.1-131.4) vs. 81.7 (58.6-112.4) μg/mL, P < 0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7 (0.8-3.4) vs. 1.1 (0.5-2.2) mg/L; white blood cell count, (6.48 ± 1.68) vs. (6.11 ± 1.67) × 109/L]. The levels of apoCIII and inflammatory markers increased with the number of metabolic risk components (all P < 0.001). Furthermore, apoCIII levels were associated with virtually all individual MetS risk factors and inflammatory markers (all P < 0.05). Importantly, the prevalence of MetS in each metabolic disorder rose as apoCIII levels increased (all P < 0.05). Mediation analysis showed that apoCIII partially mediated the effect of inflammation on MetS independently from triglycerides.

CONCLUSIONPlasma apoCIII levels were significantly associated with the development and severity of MetS, and a role of apoCIII in the effect of inflammation on the development of MetS was identified.

Adult ; Aged ; Apolipoprotein C-III ; blood ; Biomarkers ; blood ; C-Reactive Protein ; metabolism ; Coronary Angiography ; Cross-Sectional Studies ; Female ; Humans ; Inflammation ; blood ; Leukocyte Count ; Male ; Metabolic Syndrome ; blood ; Middle Aged