The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease

Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs. Objectives: to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Results: six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction. Conclusion: the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term. Graphical abstract

Plasma sgp130 is an independent predictor of non-alcoholic fatty liver disease severity

Background: Nonalcoholic steatohepatitis (NASH) is a metabolic disease associated with liver failure and cancer. Accurate monitoring of advancing NASH is challenging. There are few reliable, non-invasive biomarkers of early NASH. Since liver inflammation is a main driver of fibrosis, we investigated relationships between circulating components of the interleukin-6 signaling pathway (IL-6, sIL-6R and sgp130) and liver pathology in subjects with NAFLD and NASH. Methods: Predictive performance of plasma IL-6, sIL-6R and sgp130 were investigated in two independent cohorts: 1) patients with biopsy-confirmed NASH (n=49), where magnetic resonance spectroscopy (MRS), imaging (MRI) and elastography (MRE) assessed liver fat, volume and stiffness; and 2) patients with morbid obesity (n=245) undergoing bariatric surgery where Bedossa algorithm and steatosis, activity, and fibrosis scores assessed NASH severity. Correlations were evaluated between circulating IL-6, sIL-6R and sgp130 and anthropomorphic characteristics, plasma markers of metabolic disease or liver pathology, adjusting for covariates of liver disease such as age, sex, BMI and diabetes. Results: In patients with NASH, plasma IL-6 and sgp130 strongly correlated with liver stiffness, which for sgp130, was independent of age, sex, BMI, and chronic disease (diabetes, hyperlipidemia, hypertension or history of HCC). Plasma sgp130 was the strongest predictor of liver stiffness compared to commonly used biomarkers and predictive algorithms. Plasma sIL-6R correlated with liver volume independent of age, sex, and BMI. In stepwise forward regression analysis, plasma sgp130 followed by NAFLD fibrosis score and plasma globulin, predicted up to 74% of liver stiffness with/without adjustment for sex. In morbidly obese subjects, circulating IL-6 correlated with hepatocellular ballooning and sgp130 correlated with advanced liver fibrosis. Conclusions: Circulating sgp130 could represent a robust biomarker of active NASH and may be used alone or in combination with other biomarkers as a non-invasive measure of liver disease severity.

Tryptophan Metabolism Is Associated with BMI and Adipose Tissue Mass and Linked to Metabolic Disease in Pediatric Obesity

The obesity epidemic has contributed to an escalating prevalence of metabolic diseases in children. Overnutrition leads to increased tryptophan uptake and availability. An association between the induction of the tryptophan catabolic pathway via indoleamine 2,3-dioxygenase (IDO) activity and obesity-related inflammation has been observed. This study aimed to investigate the impact of pediatric obesity on tryptophan metabolism and the potential relationship with metabolic disease. In this prospective cohort study, plasma kynurenine, tryptophan, and serotonin levels were measured by ELISA, and IDO activity was estimated by calculating the kynurenine/tryptophan ratio in a clinically characterized population with severe obesity (BMI ≥ 97th percentile) aged 9 to 19 (n = 125). IDO activity and its product kynurenine correlated with BMI z-score and body fat mass, whereas concentrations of serotonin, the alternative tryptophan metabolite, negatively correlated with these measures of adiposity. Kynurenine and tryptophan, but not serotonin levels, were associated with disturbed glucose metabolism. Tryptophan concentrations negatively correlated with adiponectin and were significantly higher in prediabetes and metabolically unhealthy obesity. In conclusion, BMI and body fat mass were associated with increased tryptophan catabolism via the kynurenine pathway and decreased serotonin production in children and adolescents with severe obesity. The resulting elevated kynurenine levels may contribute to metabolic disease in obesity.

Risk of Glaucoma Associated with Components of Metabolic Disease in Taiwan: A Nationwide Population-Based Study

Purpose: This retrospective cohort study was conducted to determine the glaucoma risk associated with metabolic disease (MetD) using insurance claims data of Taiwan. Methods: From the database, we identified patients with newly diagnosed hypertension, diabetes and/or hyperlipidemia from the years 2000 to 2002 as the MetD cohort (N = 42,036) and an age-gender-diagnosis-date matched control cohort without MetD with a two-fold sample size than that of the MetD cohort. Both cohorts were followed until the development of glaucoma, death, or withdrawal, until December 31, 2013. The incidence of glaucoma, and the Cox method estimated hazard ratio (HR) of glaucoma were calculated. Results showed that the incidence of glaucoma was two-fold higher in the MetD cohort than in the controls (1.99 versus 0.99 per 1000 person-years), with an adjusted HR of 1.66 (95% CI: 1.50–1.85). The glaucoma incidence was higher in patients with diabetes than those with hypertension and hyperlipidemia (2.38 versus 1.95 and 1.72 per 1000 person-years, respectively). The incidence increased to 5.67 per 1000 person-years in patients with all three comorbidities, with an aHR of 4.95 (95% CI: 2.35–10.40). We also found higher incidence rates of primary open-angle glaucoma and primary angle-closure glaucoma with aHRs of 2.03 and 1.44, respectively. It was concluded that glaucoma risk increased with the number of MetD. Health providers need to monitor patients with MetD to prevent glaucoma.

A Review on the Structure and Anti-Diabetic (Type 2) Functions of β-Glucans

Type 2 diabetes, a long-term chronic metabolic disease, causes severe and increasing economic and health problems globally. There is growing evidence that β-glucans can function as bioactive macromolecules that help control type 2 diabetes with minimal side effects. However, conflicting conclusions about the antidiabetic activities of β-glucans have been published, potentially resulting from incomplete understanding of their precise structural characteristics. This review aims to increase clarity on the structure–function relationships of β-glucans in treating type 2 diabetes by examining detailed structural and conformational features of naturally derived β-glucans, as well as both chemical and instrumental methods used in their characterization, and their underlying anti-diabetic mechanisms. This may help to uncover additional structure and function relationships and to expand applications of β-glucans.

The Potential Mechanism of Exercise Combined with Natural Extracts to Prevent and Treat Postmenopausal Osteoporosis

Postmenopausal osteoporosis (PMOP) is a systemic chronic bone metabolic disease caused by the imbalance between bone formation and bone resorption mediated by estrogen deficiency. Both exercise and natural extracts are safe and effective means to prevent and control PMOP. The additive effect of exercise synergy extract against PMOP may be no less than that of traditional medicine. However, the mechanism of action of this method has not been clarified in detail. A large number of studies have shown that the pathogenesis of PMOP mainly involves the OPG-RANKL-RANK system, inflammation, and oxidative stress. Based on the abovementioned approaches, the present study reviews the anti-PMOP effects and mechanisms of exercise and natural extracts. Finally, it aims to explore the possibility of the target of the two combined anti-PMOP through this approach, thereby providing a new perspective for joint intervention research and providing a new direction for the treatment strategy of PMOP.

Aging Leukocytes and the Inflammatory Microenvironment of the Adipose Tissue

Age-related immunosenescence, defined as an increase in inflammaging and the decline of the immune system, leads to tissue dysfunction and increased risk for metabolic disease. The elderly population is expanding, leading to a heightened need for therapeutics to improve health span. With age, many alterations of the immune system are observed, including shifts in the tissue-resident immune cells, increased expression of inflammatory factors, and the accumulation of senescent cells, all of which are responsible for a chronic inflammatory loop. Adipose tissue and the immune cell activation within are of particular interest for their well-known roles in metabolic disease. Recent literature reveals that adipose tissue is an organ in which signs of initial aging occur, including immune cell activation. Aged adipose tissue reveals changes in many innate and adaptive immune cell subsets, revealing a complex interaction that contributes to inflammation, increased senescence, impaired catecholamine-induced lipolysis, and impaired insulin sensitivity. Here, we will describe current knowledge surrounding age-related changes in immune cells while relating those findings to recent discoveries regarding immune cells in aged adipose tissue.