Aging reveals a sex-dependent susceptibility of sarcospan-deficient mice to cardiometabolic disease.

Numerous genes including sarcospan (SSPN) have been designated as obesity-susceptibility genes by human genome-wide association studies. Variants in the SSPN locus have been linked with sex-dependent obesity-associated traits; however, this association has not been investigated in vivo. To delineate the role SSPN plays in regulating metabolism with potential to impact cardiac function, we subjected young and aged global SSPN-deficient (SSPN-/-) male and female mice to obesogenic conditions (60% fat diet). We hypothesized that loss of SSPN combined with metabolic stress would increase susceptibility of mice to cardiometabolic disease. Baseline and end-point assessments of several anthropometric parameters were performed including weight, glucose tolerance, and fat distribution of mice fed control (CD) and high-fat (HFD) diet. Doppler echocardiography was used to monitor cardiac function. White adipose and cardiac tissues were assessed for inflammation by histological, gene expression, and cytokine analysis. Overall, SSPN deficiency protected both sexes and ages from diet-induced obesity, with a greater effect in females. SSPN-/- HFD mice gained less weight than wild-type (WT) cohorts, while SSPN-/- CD groups increased weight. Furthermore, aged SSPN-/- mice developed glucose intolerance regardless of diet. Echocardiography showed preserved systolic function for all groups; however, aged SSPN-/- males exhibited significant increases in left ventricular mass (CD) and signs of diastolic dysfunction (HFD). Cytokine analysis revealed significantly increased IL-1α and IL-17Α in white adipose tissue from young SSPN-/- male mice, which may be protective from diet-induced obesity. Overall, these studies suggest that several sex-dependent mechanisms influence the role SSPN plays in metabolic responses that become evident with age.NEW & NOTEWORTHY Young and aged sarcospan (SSPN)-deficient mice were examined to assess the role of SSPN in obesity and cardiometabolic disease. Both sexes displayed a "leaner" phenotype in response to high-fat diet (HFD). Notably, several sex differences were identified in aged SSPN-deficient mice: 1) females developed glucose intolerance (control and HFD) and 2) males exhibited increased left ventricular mass (control) and diastolic dysfunction (HFD). Therefore, we conclude that SSPN exerts a sex-dependent influence on obesity-associated diseases.

Therapeutic potential of Lactobacillus casei and Chlorella vulgaris in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD)-associated kidney damages: a stereological study.

BACKGROUND: The non-alcoholic fatty liver disease (NAFLD) is prevalent in as many as 25% of adults who are afflicted with metabolic syndrome. Oxidative stress plays a significant role in the pathophysiology of hepatic and renal injury associated with NAFLD. Therefore, probiotics such as Lactobacillus casei (LBC) and the microalga Chlorella vulgaris (CV) may be beneficial in alleviating kidney injury related to NAFLD. MATERIALS AND METHODS: This animal study utilized 30 C57BL/6 mice, which were evenly distributed into five groups: the control group, the NAFLD group, the NAFLD + CV group, the NAFLD + LBC group, and the NAFLD + CV + LBC group. A high-fat diet (HFD) was administered to induce NAFLD for six weeks. The treatments with CV and LBC were continued for an additional 35 days. Biochemical parameters, total antioxidant capacity (TAC), and the expression of kidney damage marker genes (KIM 1 and NGAL) in serum and kidney tissue were determined, respectively. A stereological analysis was conducted to observe the structural changes in kidney tissues. RESULTS: A liver histopathological examination confirmed the successful induction of NAFLD. Biochemical investigations revealed that the NAFLD group exhibited increased ALT and AST levels, significantly reduced in the therapy groups (p < 0.001). The gene expression levels of KIM-1 and NGAL were elevated in NAFLD but were significantly reduced by CV and LBC therapies (p < 0.001). Stereological examinations revealed reduced kidney size, volume, and tissue composition in the NAFLD group, with significant improvements observed in the treated groups (p < 0.001). CONCLUSION: This study highlights the potential therapeutic efficacy of C. vulgaris and L. casei in mitigating kidney damage caused by NAFLD. These findings provide valuable insights for developing novel treatment approaches for managing NAFLD and its associated complications.

Resveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis of randomized controlled trials.

We perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify the effect of resveratrol supplementation on endothelial function. A comprehensive search was performed in electronic databases including PubMed, Scopus, Web of Science, and Cochrane Library up to February 2021 with no limitation in time and language. A meta-analysis of eligible studies was performed using a random-effects model to estimate the pooled effect size of flow-mediated dilation (FMD), intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). In total, 21 arms from 17 studies were included. The meta-analysis results showed that resveratrol significantly change the concentrations of FMD (WMD: 1.43%; 95% CI: 0.98 to 1.88, p < .001) and ICAM-1 (WMD: -7.09 ng/ml, 95% CI: -7.45 to -6.73, p < .001). However, VCAM-1, fibrinogen, and PAI-1 did not change significantly after resveratrol supplementation. In conclusion, the results of this study suggest that resveratrol supplementation can improve endothelial function which could be important, especially in patients with cardiovascular diseases.

The effects of zinc supplementation on the metabolic factors in patients with non-alcoholic fatty liver disease: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic factors including obesity, dyslipidemia, insulin resistance, oxidative stress, and elevated inflammatory factors. Zinc (Zn) supplementation has been investigated as a potential adjunctive therapy in managing NAFLD outcomes. METHODS: In this randomized, double-blinded, controlled clinical trial, 50 overweight or obese participants with NAFLD were randomized into 2 groups of 25 and received either 30 mg of daily Zn or a placebo for 8 weeks. Both groups were invited to follow a balanced energy-restricted diet and physical activity recommendations. RESULTS: Based on the between-group comparison, Zn supplementation caused a significant increase in the Zn level (P < 0.001) and a significant decrease in weight (P = 0.004), body mass index (BMI) (P = 0.002), waist circumference (P = 0.010), aspartate transaminase (AST) (P = 0.033), total cholesterol (TC) (P = 0.045), and low-density lipoprotein cholesterol (LDL-C) (P = 0.014), but it had no significant effect on alanine transaminase (ALT), fasting blood sugar (FBS), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high-density lipoprotein (HDL), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and total antioxidant capacity (TAC) (P > 0.05). CONCLUSION: The results of the present study indicated that 8-week supplementation of 30 mg daily Zn may increase the Zn serum level and decline anthropometric parameters, AST, TC, and LDL-C in NAFLD patients, so further research is suggested in the future. TRIAL REGISTRATION: The trial was retrospectively registered at IRCT.ir as IRCT20191015045113N1 (December/8/2019).

Intake of Various Food Groups and Risk of Breast Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Despite increasing evidence for the association of food-based dietary patterns with breast cancer risk, knowledge about the shape of the relationship and the quality of meta-evidence are insufficient. We aimed to summarize the associations between food groups and risks of breast cancer. We performed a systematic literature search of the PubMed and Embase databases up to March 2020. We included cohort, case-cohort, nested case-control studies, and follow-up studies of randomized controlled trials that investigated the relationship between breast cancer risk and at least 1 of the following food groups: red meat, processed meat, fish, poultry, egg, vegetables, fruit, dairy product (overall, milk, yogurt, and cheese), grains/cereals, nuts, legumes, soy, and sugar-sweetened beverages. Summary risk ratios (RRs) and 95% CIs were estimated using a random-effects model for linear and nonlinear relationships. Inverse linear associations were observed for vegetables (RR per 100 g/d, 0.97; 95% CI, 0.95-0.99), fruit (RR per 100 g/d, 0.97; 95% CI, 0.95-0.99), cheese (RR per 30 g/d, 0.95; 95% CI, 0.91-1.00), and soy (RR per 30 g/d, 0.96; 95% CI, 0.94-0.99), while positive associations were observed for red (RR per 100 g/d, 1.10; 95% CI, 1.03-1.18) and processed meat (RR per 50 g/d, 1.18; 95% CI, 1.04-1.33). None of the other food groups were significantly associated with breast cancer risk. A nonlinear association was observed only for milk, such that the intake of >450 g/d increased the risk, while no association was observed for lower intake amounts. High intakes of vegetables, fruit, cheese, and soy products and low intakes of red and processed meat were associated with lower risks of breast cancer. However, causality cannot be inferred from these statistical correlations.