Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-ß genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). METHODS: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1α (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-ß between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. CONCLUSION: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".

The effect of L-carnitine supplementation on lipid profile in adults: an umbrella meta-analysis on interventional meta-analyses.

Introduction: Previous meta-analyses investigating the therapeutic effects of L-carnitine on lipid profiles have demonstrated inconsistent results. The present umbrella meta-analysis aimed to investigate the impact of efficacy of L-carnitine on lipid profiles in adults. Methods: Databases including PubMed, Scopus, and Embase, Web of Science, and Google Scholar were searched up to June 2023. Meta-analysis was performed using a random-effects model. Results: Our results from thirteen meta-analyses indicated that L-carnitine supplementation significantly total cholesterol (TC) (ES = -1.05 mg/dL, 95% CI: -1.71, -0.39; p = 0.002), triglycerides (TG) (ES = -2.51 mg/dL; 95% CI: -3.62, -1.39, p < 0.001), and low-density lipoprotein-cholesterol (LDL-C) (ES = -4.81 mg/dL; 95% CI: -6.04, -3.59; p < 0.001). It also increased high-density lipoprotein-cholesterol (HDL-C) (ES: 0.66 mg/dL, 95% CI: 0.20, 1.12, p = 0.005) levels. Conclusion: The present umbrella meta-analysis suggests supplementation with L-carnitine in a dosage of more than 2 g/day can improve lipid profile. Thus, L-carnitine supplementation can be recommended as an adjuvant anti-hyperlipidemic agent.

The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Obesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet. METHODS: This triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit. DISCUSSION: New evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20190303042905N2 . Registered on 31 January 2021.

Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of metabolic syndrome is closely associated with type 2 diabetes mellitus. Myo-inositol (MI)-a 6-C sugar alcohol-with insulin-mimetic, anti-diabetic, lipid-lowering, and anti-inflammatory properties has exerted favorable effects on insulin resistance-related disorders and metabolic disease, while recent animal studies revealed its positive effects on liver function. This study aimed to investigate the effects of MI supplementation on cardiometabolic factors, anthropometric measures, and liver function in obese patients with NAFLD. Methods: This double-blinded placebo-controlled randomized clinical trial was carried out on 48 obese patients with NAFLD who were randomly assigned to either MI (4g/day) or placebo (maltodextrin 4g/day) along with dietary recommendations for 8 weeks. Glycemic indices, lipid profile, liver enzymes anthropometric measures, and blood pressure were evaluated pre- and post-intervention. Dietary intakes were assessed using a 3-day 24 h recall and analyzed by Nutritionist IV software. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and beta-cell function (HOMA-B) was also estimated. Results: Anthropometric measures decreased significantly in both groups, while the reduction in weight (p = 0.049) and systolic blood pressure (p = 0.006) in the MI group was significantly greater than in the placebo group after adjusting for baseline values and energy intake. Although energy and macronutrient intakes decreased significantly in both groups, between-group differences were not significant after adjusting for the potential confounders. MI supplementation led to a significant reduction in serum fasting insulin (p = 0.008) and HOMA-IR (p = 0.046). There were significant improvements in lipid profile, liver enzymes, and aspartate aminotransferase/alanine aminotransferase ratio as well as serum ferritin level in the MI group, compared to the placebo group at the endpoint. By MI supplementation for eight weeks, 1 in 3 patients reduced one- grade in the severity of NAFLD. Conclusion: MI supplementation could significantly improve IR, lipid profile, and liver function in patients with NAFLD. Further clinical trials with larger sample sizes, longer duration, different MI doses, and other inositol derivatives are recommended.

The roles of quercetin in diabetes mellitus and related metabolic disorders; special focus on the modulation of gut microbiota: A comprehensive review.

Quercetin is a dietary flavonoid that can affect the balance between anti-oxidant defense system and oxidative stress. A number of studies showed the positive effects of quercetin on diabetes mellitus and related metabolic disorders through different pathways such as gut flora. However, findings are conflicting. In addition, it seems no studies have summarized all potential mechanisms of quercetin in diabetes mellitus, so far. Therefore, the aims of the present comprehensive review were to provide an overview on biological and biochemical characteristics of quercetin and investigate the effect of quercetin on diabetes mellitus and related metabolic disorders by focusing on its effects on the modulation of gut microbiota. For this purpose, findings of In vitro, animal studies, clinical trials, and review studies with the English language published until January 2021 were summarized. They were identified through electronic databases (PubMed, Scopus, and Cochrane Library) and Google Scholar. Findings showed that quercetin can be an effective component for improving glycemic status and other metabolic disorders related to diabetes mellitus based on In vitro and animal studies. However, environmental factors, food processing and using nanoformulations can affect its efficacy in human studies. Several potential mechanisms, including the modulation of gut flora are proposed for its actions. However, due to limited clinical trials and contradictory findings, more high-quality clinical trials are needed to make a decision on the efficacy of supplementation with quercetin as a complementary therapy for the management of diabetes mellitus, metabolic disorders, and modulating gut flora.

The effect of saffron (Crocus sativus L.) on glycemia, lipid profile, and antioxidant status in patients with type-2 diabetes mellitus: A randomized placebo-controlled trial.

In the current study, we aimed to investigate the effect of saffron supplementation on glycemic status, lipid profile, atherogenic indices, and oxidative status in patients with type-2 diabetes (T2DM). In a randomized, double-blind controlled trial, 70 patients were randomly allocated into two groups (n = 35, each) and received 100 mg/day of saffron or placebo for eight weeks. Dietary intake, weight, body mass index (BMI), waist and hip circumferences (WC and HC), waist to hip ratio (WHR), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, and Homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile, atherogenic indices, oxidative status, and liver enzymes were determined before and after the intervention. At the end of the eighth week, saffron intervention could significantly reduce FBS (7.57%), lipid profile (except high-density lipoprotein cholesterol [HDL-C]), atherogenic indices, and liver enzymes (p < .05). Moreover, saffron could improve oxidative status (nitric oxide [NO] and malondialdehyde [MDA] reduced by 26.29% and 16.35%, respectively). Catalase (CAT) concentration remained unchanged. Saffron supplementation may alleviate T2DM by improving glycemic status, lipid profile, liver enzymes, and oxidative status. Further investigation is necessary to assess possible side effects and confirm the positive effect of saffron as a complementary therapy in clinical recommendations for T2DM.

The effects of butyrate supplementation on glycemic control, lipid profile, blood pressure, nitric oxide level and glutathione peroxidase activity in type 2 diabetic patients: A randomized triple -blind, placebo-controlled trial.

BACKGROUND: This study aimed to investigate the effects of oral NaBut on metabolic parameters, blood pressure, and oxidative stress indices including glutathione peroxidase (GPx) and nitric oxide (NO) status in type 2 diabetic patients. METHODS: In the current interventional trial, 42 patients with type 2 diabetes mellitus (T2DM) were randomly allocated into either NaBut (n = 21) or placebo (n = 21) group for six weeks. Serum concentrations of metabolic parameters, GPx, NO as well as blood pressure were assessed before and after the intervention. RESULTS: Within-group findings demonstrated that NaBut administration significantly reduced systolic and diastolic blood pressure (p = 0.016 and p = 0.002, respectively). Blood sugar 2-hr postprandial (BS2hpp) was also significantly decreased in the intervention and placebo groups (p = 0.016 and p = 0.019, respectively), but the between-group differences were not statistically significant. Differences in homeostatic model assessment of insulin resistance (HOMA-IR) were not significant between groups after adjustment for potential confounders (p = 0.061). NaBut supplementation was also found to significantly increase total cholesterol (p = 0.001), low-density lipoprotein cholesterol (p = 0.005), and insulin levels (p = 0.047) compared to the baseline, while decreased NO levels (p = 0.040). However, there were no significant between-group differences in these parameters. No significant differences were also found in other parameters. CONCLUSIONS: We observed significant within-group decreases in systolic and diastolic blood pressure as well as BS2hpp following oral butyrate treatment. While no or even adverse changes in other biochemical parameters were found. Further investigations with longer durations are warranted to more vividly elucidate the effects of NaBut supplementation on patients with T2DM. Registered under Iranian Registry of Clinical Trials website (http://www.irct.ir), Identifier no. IRC T20090609002017N33.

Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: Effects on the expression of pyroptosis-related genes and oxidative stress status.

BACKGROUND AND AIMS: Atherosclerosis as a chronic inflammatory disorder of the arterial wall is the main leading cause of the cardiovascular disease (CVD). Caspase-dependent pyroptosis plays a pivotal role in the pathogenesis of CVD. Selenium (Se) is an important component of the antioxidant defense and plays a crucial role in cardiovascular health. This study aimed to investigate the effects of daily consumption of sodium selenite and Se-enriched yeast on the expression of pyroptosis-related genes, and biomarkers of oxidative stress in patients with atherosclerosis. METHODS AND RESULTS: In this randomized, double-blinded, placebo-controlled clinical trial, 60 patients with atherosclerosis were recruited. Participants received 200 µg/day of sodium selenite, Se-enriched yeast, or placebo for 8 following weeks. The pyroptosis-related genes' mRNA expression in peripheral blood mononuclear cells (PBMCs) was assessed before and after the intervention. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidases (GPX) were measured at baseline and following the intervention. Following sodium selenite and Se-enriched yeast supplementation, the relative expression levels of TLR4, ASC, NLRP3, and NF-κB1 were significantly downregulated (p < 0.05). Furthermore, the changes in GPX were significantly increased after selenite and yeast supplementation (p < 0.05). Also, selenite and yeast consumption caused a statistically significant decrease in the change of MDA level (p < 0.05). CONCLUSION: In summary, these findings showed that Se supplementation may reduce inflammation through down-regulation of some pro-inflammatory genes, improving antioxidant defenses in atherosclerosis patients. Further research is required to come to a definite conclusion of selenium supplementation on the CVD risk. This study was registered on the Iranian Registry of Clinical Trials website (identifier: RCT20110123005670N28; https://www.irct.ir/).

The therapeutic potential of Crocus sativus Linn.: A comprehensive narrative review of clinical trials.

Crocus sativus Linn. (Saffron) is valued worldwide for its potential use in the management of various degenerative disorders, including cardiovascular diseases (CVDs), diabetes, cancer, metabolic syndrome (MetS), neurodegenerative diseases, immune disorders, and sexual dysfunction. Previous reports, based on clinical trials, suggest that crocetin, crocin, picrocrocin, and safranal are the main bioactive components of saffron with antioxidant, anti-inflammatory, and anti-apoptotic effects. In this comprehensive narrative review, we studied the recent clinical trials, investigating the medicinal applications of saffron and/or its components. The present results can provide important insights into the potential of saffron in preventing and treating different disorders, with a special focus on the underlying cellular and molecular mechanisms. However, further high-quality studies are needed to firmly establish the clinical efficacy of saffron in treating some degenerative diseases.

Saffron improves life and sleep quality, glycaemic status, lipid profile and liver function in diabetic patients: A double-blind, placebo-controlled, randomised clinical trial.

BACKGROUND: Type 2 diabetes (T2D) is a metabolic disorder that is related to hyperglycaemia, hyperlipidaemia and liver dysfunction and has detrimental effects on a patient's mental health. Hence, the current study investigated the effects of saffron supplementation on dietary intake, anthropometric measures, mood, sleep quality and metabolic biomarkers in overweight/obese patients with T2D. METHODS: In a double-blind, randomised controlled trial, 70 overweight/obese patients with T2D were randomly allocated to two groups and received 100 mg/day saffron or placebo for 8 weeks. Participants completed the Beck depression inventory-II (BDI-II), Hurlbert index of sexual desire (HISD), Pittsburgh Sleep Quality Index (PSQI) and Diabetes-specific Quality-of-Life Brief Clinical Inventory questionnaires (DQOL-BCI). Dietary intake, anthropometric measures, fasting plasma glucose (FPG), haemoglobin A1C (HbA1C), insulin, lipid profile and liver enzymes were determined at baseline and the end of the study. RESULTS: At the end of the eighth week, saffron supplementation significantly decreased FPG, triglyceride (TG), insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < .001). Moreover, significant improvements in BDI-II scores and total quality of life were observed in the intervention group (P < .001). The saffron group showed more significant improvements in PSQI scores than the placebo group, such that at the post-intervention analysis, only the saffron group achieved a "good" sleep band. At this relatively high dose, saffron supplementation improved glycaemic status, lipid profile and liver enzyme measures in patients with T2D while also improving sleep and overall quality of life. CONCLUSION: Our results indicate that saffron notably reduced hyperglycaemia and hyperlipidaemia and improved liver function in patients with T2D in an 8-week randomised clinical trial. Saffron also significantly improved depression, sleep quality and overall quality of life in diabetic patients. However, further investigation is necessary to confirm whether saffron is an effective complementary therapy for T2D.

Systematic review and meta-analysis of randomised, controlled trials on the effects of garlic supplementation on serum adiponectin and leptin levels.

BACKGROUND: Our aim in this meta-analysis was to determine the effect of garlic supplementation on adiponectin and leptin serum levels. METHOD: A systematic search was conducted using PubMed, Scopus, ISI Web of Science and Cochrane Library for eligible trials up to November 2020. A fixed-effects model was used to pool calculated effect sizes. RESULTS: Five trials were included in the overall analysis. Our analysis showed that garlic supplementation did not significantly affect adiponectin (Hedges's: 0.20; 95% CI: -0.06, 0.47; P-values = .12) and leptin (Hedges's: 0.08; 95% CI: -0.26, 0.41; P-values = .65) concentrations in comparison with placebo. However, in the subgroup analysis, significantly increased serum adiponectin level was seen following garlic supplementation in trials with a mean age of participants ˂30 years (Hedges's: 0.44; 95% CI: 0.01, 0.87; P-values = .04), the doses ˂1.5 g/d (Hedges's: 0.38; 95% CI: 0.02, 0.71; P-values = .04) and trials with duration ≥8 weeks (Hedges's: 0.48; 95% CI: 0.08, 0.89; P-values = .02). CONCLUSION: Overall, garlic supplementation could not change the circulatory adiponectin and leptin levels. Subgroup analyses showed a significant reduction in adiponectin levels in younger participants, longer duration and lower intervention dose. However, further studies are needed to confirm the present results.

Effects of sodium selenite and selenium-enriched yeast on cardiometabolic indices of patients with atherosclerosis: A double-blind randomized clinical trial study.

Introduction: Atherosclerosis and related cardiovascular diseases (CVDs) are the major causes of mortality worldwide. The available reports regarding the effects of selenium (Se) supplementation in the realm of atherosclerosis have been equivocal. The present investigation is aimed to assess the effects of sodium selenite and Se-enriched yeast supplementation on metabolic parameters among atherosclerotic patients. Methods: In this double-blind placebo-controlled randomized clinical trial, 60 patients diagnosed with atherosclerosis were randomly allocated into either 200 µg/day selenite, yeast, or placebo groups for eight consecutive weeks. Serum levels of lipid profile and glycemic indices were measured at the baseline and end of the intervention. Results: There were no significant within-or between-group changes in levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), fasting blood sugar, insulin, and homeostatic model assessment for IR throughout the study (P ≥0.05). Only the low density lipoprotein cholesterol (LDL-c) levels were significantly lower in the yeast group in comparison with the placebo group (P = 0.015). Conclusion: The administration of Se-enriched yeast is significantly effective in decreasing LDL-c levels in patients with atherosclerosis. Additional clinical trial studies investigating the effect of Se administration on glucose homeostasis parameters and lipid profiles in atherosclerotic patients are suggested for a more definitive conclusion.

Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common noncommunicable diseases worldwide. The present study aimed to investigate the effects of oleoylethanolamide (OEA) supplementation combined with calorie restriction on inflammation, body composition, and hepatic fibrosis among obese patients with NAFLD. In this 12-week randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group. The weight-loss diet was also designed for both groups. Pre- and postintervention messenger RNA expression levels of the transcription factor nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and IL-10, body composition, and NAFLD fibrosis score were assessed. At the end of the study, the OEA group showed lower NF-κB and IL-6 expression levels compared to the placebo (p < .01). However, IL-10 expression level was approximately twofold higher in the OEA group compared to the placebo group (p = .008). A significant reduction was observed in the fat mass of the OEA group compared to the placebo (p = .044) postintervention. In addition, OEA supplementation led to a significant increase in fat-free mass in the OEA group compared to the placebo (p = .032). A remarkable increase was observed in resting metabolic rate (RMR) in the OEA group (p = .009); however, it was not found in the placebo group. There were no significant between-group differences in RMR postintervention. In addition, no significant within-and between-group differences were observed in the NAFLD fibrosis score at the end of the trial. Treatment with OEA along with weight-loss intervention could significantly improve inflammation and body composition in patients with NAFLD.

What is the Impact of Cinnamon Supplementation on Blood Pressure? A Systematic Review and Meta-Analysis.

AIM: This study was designed to make a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of cinnamon on blood pressure (BP). METHODS: A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar databases was conducted up to August 2019. All RCTs using cinnamon supplements in adults were included in this systematic review and meta-analysis. RESULTS: Out of 927 records, 8 trials that enrolled 582 participants were included. The pooled effect size showed that SBP did not change following cinnamon supplementation. (WMD: -0.61mmHg; 95% CI: -1.36, 0.14, P= 0.111). Also cinnamon supplementation in long-duration (≥ 8weeks) had a significant effect on SBP (WMD: -1.25 mmHg; 95% CI: -2.22, -0.28, P= 0.012). Pooled analysis showed that cinnamon had a significant effect on DBP (WMD: -0.93mmHg, 95% CI: -1.55 to -0.32, P= 0.003). In addition, results from both duration subsets and high dose (>1500 mg/day) of cinnamon supplementation were significant. CONCLUSION: Our findings revealed that cinnamon supplementation has favorable effects on DBP although results of SBP were not the same. Nonetheless, further studies are required.

Is there any association between fruit consumption and the risk of gestational diabetes mellitus? A systematic review and meta-analysis.

AIM: Although a considerable number of studies have illustrated the positive effects of fresh fruits on metabolic status, the impacts of fruits on the risk of gestational diabetes mellitus (GDM) are inconsistent. In consideration of this issue, we aimed to systematically summarize the findings of cohort studies with respect to the link between fresh fruits and the risk of GDM. METHOD: We selected cohort studies with English language indexed in PubMed/Medline, Scopus, Web of Science, and Embase from 2000 to 31 January 2018. To examine the link between fresh fruits and the risk of GDM development, relative risk (RR) and 95 % confidence intervals (CIs) for the highest versus the lowest consumption of fruits were pooled using a random effect model and the DerSimonian and Laird method. RESULTS: Out of 2522 publications, finally 5 cohort studies were obtained. No significant association between fruit consumption and GDM incidence was found (Pooled RR: 0.95; 95 % CI: 0.84, 1.08; I2: 90.3 %, p = 0001). In women who consumed higher amount of fruits before pregnancy, the risk of GDM was 5% lower than in those who consumed lower amount of fruits (0.95; 95 %CI: 0.91, 0.99, I2: 0%, p = 0.85). No link was obtained between fruit consumption during the pregnancy and GDM onset (1.18, 95 % CI: 0.48, 2.91; I2:94.6 %, p = 0.0001). CONCLUSION: In women who consumed greater fruits before pregnancy, the risk for GDM was 5 % lower than those consumed lower amounts of fruits, while there was no link between fruit consumption throughout the pregnancy and GDM onset. However, due to limited studies and considerable heterogeneity, the findings must be interpreted with great caution.

The effects of royal jelly and tocotrienol-rich fraction on impaired glycemic control and inflammation through irisin in obese rats.

The effects of royal jelly (RJ) and tocotrienol-rich fraction (TRF) on obesity-induced glucose intolerance and inflammation were assessed in the current study. Regarding irisin as an important adipomyokine that attenuates obesity-induced disorders, we evaluated whether RJ and TRF could exert their metabolism regulatory effects through irisin. Obese rats were fed a high-fat diet (HFD) with or without supplementation of RJ, TRF, or both, for 8 weeks. At the end of the intervention, weight, irisin, glycemic, and inflammatory indices were measured. The weight of the rats did not remarkably reduce in any of the groups. Glucose homeostasis and inflammation were improved when we added RJ and TRF to HFD. RJ elevated irisin concentration, but the effect of TRF on irisin was not noticeable. Our results indicated that, despite the lack of significant weight loss, RJ and TRF promoted healthy obesity. This improvement was mediated by irisin in RJ consuming rats. PRACTICAL APPLICATIONS: Obesity is a public health concern associated with several chronic disorders. The beneficial effects of irisin on obesity-related disorders are well-established. It is the first study assessing the effect of RJ and TRF as functional foods, with pharmacological and nutritional activities on obesity complications, through irisin mediation. Our study demonstrated that RJ exerts its metabolic regulatory effects by irisin as a mediator. Our investigation makes a remarkable contribution to the literature, because it suggests a new mechanism for the anti-obesity properties of RJ and TRF.

Effects of Royal Jelly and Tocotrienol Rich Fraction in obesity treatment of calorie-restricted obese rats: a focus on white fat browning properties and thermogenic capacity.

BACKGROUND: Obesity has reached an alarming rate worldwide. Promoting thermogenesis via increasing the function of brown adipose tissue (BAT) or white adipose tissue (WAT) browning has been proposed as a new protective approach against obesity. The goal of this study was to evaluate the effects of Royal Jelly (RJ) and tocotrienol rich fraction (TRF) on BAT activation and WAT browning during calorie restriction diet (CRD) in obesity model. METHODS: In this experimental study, 50 obese Wistar rats were randomly divided into 5 groups and then received one of the following treatments for a period of 8-week: High-fat diet (HFD), CRD, RJ + CRD, TRF + CRD, and RJ + TRF + CRD. Effects of RJ and TRF, individually and in combination on body weight and the expression of key thermoregulatory genes in WAT and BAT were examined by quantitative real-time (qRT-PCR). Also, morphological alterations were assessed by hematoxylin and eosin staining. RESULTS: RJ (- 67.21 g ±4.84 g) and RJ + TRF (- 73.29 g ±4.51 g) significantly reduced weight gain relative to the CRD group (- 40.70 g ±6.50 g, P < 0.001). In comparison with the CRD group, RJ and RJ + TRF remarkably enhanced the uncoupling protein1 (UCP1) expression in WAT (5.81, 4.72 fold, P < 0.001) and BAT (4.99, 4.75 fold, P < 0.001). The expression of PR domain containing 16(PRDM 16), cAMP response element-binding protein1 (CREB1), P38 mitogen-activated protein kinases (P38MAPK), and Bone morphogenetic protein8B (BMP8B) have significantly increased following RJ and RJ + TRF treatments (P < 0.001). However, the expression levels of CCAAT/enhancer-binding protein beta (CEBPß) and Bone morphogenetic protein7 ( BMP7) did not remarkably change. Multilocular beige cells in WAT and compacted dense adipocytes were also observed in BAT of RJ and RJ + TRF received groups. TRF showed no substantial effects on the expression of the mentioned thermoregulatory genes and brown fat-like phenotype. CONCLUSION: Our results suggest that, Royal Jelly promotes thermogenesis and browning of WAT, contributing to an increase in energy expenditure. Thus, Royal Jelly may give rise to a novel dietary choice to attenuate obesity.

Effects of saffron supplementation on glycemia and inflammation in patients with type 2 diabetes mellitus: A randomized double-blind, placebo-controlled clinical trial study.

BACKGROUND: New evidence indicates that overproduction of pro-inflammatory cytokines is responsible for the development of diabetes difficulties. Some herbals such as saffron, may control inflammation and improve the hyperglycemic states in diabetic patients. Therefore, this investigation aimed to assess the effects of saffron supplementation on fasting glucose and inflammatory markers levels in patients with type2 diabetes mellitus (T2DM). METHODS: In this randomized double-blind, placebo-controlled clinical trial, 60 T2DM patients were randomly assigned into two groups as saffron and placebo (n = 30) receiving 100 mg/day saffron powder or starch capsules (1 capsule) for a duration of 8 weeks. Fasting blood sample was collected at baseline and at the end of the intervention. Fasting blood glucose (FBG) was immediately analyzed by the auto-analyzer. The serum level of Interleukin -6 (IL-6), Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) were measured using ELISA assay by laboratory kits. Also, Real-time quantitative reverse transcription (RT-PCR) assay measured the expression level of TNF-α, IL-6, and IL-10 at the mRNA level. RESULTS: Saffron supplementation significantly decreased the FBG levels within 8 weeks compared to placebo (130.93 ± 21.21 vs 135.13 ± 23.03 mg/dl, P = 0.012). Moreover, the serum level of TNF-α notably reduced in the saffron group compared to the placebo group (114.40 ± 24.28 vs 140.90 ± 25.49 pg/ml, P < 0.001). Also, saffron supplementation significantly down-regulated the expressions of TNF-α (P = 0.035) and IL-6 mRNA levels (P = 0.014). CONCLUSION: In our study, it was indicated that saffron modulates glucose levels as well as inflammation status in T2DM patients through decreasing the expressions levels of some inflammatory mediators. Also, further investigations are necessary to confirm the positive effects of saffron as a complementary therapy for T2DM patients.

Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

PURPOSE: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). METHODS: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). RESULTS: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1ß & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. CONCLUSION: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link.

Oleoylethanolamide supplementation in obese patients newly diagnosed with non-alcoholic fatty liver disease: Effects on metabolic parameters, anthropometric indices, and expression of PPAR-α, UCP1, and UCP2 genes.

The effects of oleoylethanolamide (OEA) on NAFLD are yet to be examined in human. The objective of the present study was to examine the effects of OEA supplementation along with weight loss intervention on the expression of PPAR-α, uncoupling proteins 1and 2 (UCP1 and UCP2) genes in the peripheral blood mononuclear cells (PBMCs), metabolic parameters, and anthropometric indices among obese patients with NAFLD. In this triple-blind placebo-controlled randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group along with calorie-restricted diets for 12 weeks. At pre-and post-intervention phase, mRNA expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, serum levels of metabolic parameters as well as diet and appetite sensations were assessed. There was a significant increase in the expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, compared to the placebo at the endpoint. A significant decrease in the anthropometric indices, energy and carbohydrate intakes, glycemic parameters, except for hemoglobin A1c concentration was also observed in the OEA group, compared to the placebo group. OEA treatment significantly resulted in decreased serum levels of triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, increased serum levels of high-density lipoprotein cholesterol (HDL-C), and improved appetite sensations. Importantly, a significant improvement in TG, ALT, AST, ALT/AST, HDL-C levels as well as appetite sensations by OEA were under the influence of body mass index (BMI). Although liver steatosis severity was significantly reduced in both groups, the between-group differences did not reach statistical significance (P = 0.061). In conclusion, the present study, for the first time, revealed that OEA supplementation significantly improved anthropometric and metabolic risk factors related to NAFLD.