Soluble receptor of advanced glycation end product as a biomarker in neurocognitive and neuropsychiatric disorders: A meta-analysis of controlled studies.

BACKGROUND & OBJECTIVES: Currently, there is a significant focus on the decrease of soluble receptor of advanced glycation end products (sRAGE) in neurocognitive and neuropsychiatric disorders. sRAGE plays a decoy role against the inflammatory response of advanced glycation end products (AGE), which has led to increased interest in its role in these disorders. This meta-analysis aimed to investigate the significant differences in sRAGE levels between neurocognitive and neuropsychiatric disorders compared to control groups. METHOD: A systematic review was conducted using the PUBMED, Scopus and Embase databases up to October 2023. Two reviewers assessed agreement for selecting papers based on titles and abstracts, with kappa used to measure agreement and finally publications were scanned according to controlled studies. Effect sizes were calculated as weighted mean differences (WMD) and pooled using a random effects model. Heterogeneity was assessed using I2, followed by subgroup analysis and meta-regression tests. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: In total, 16 studies were included in the present meta-analysis. Subjects with neurocognitive (n = 1444) and neuropsychiatric (n = 444) disorders had lower sRAGE levels in case-control (WMD: -0.21, 95% CI: -0.33, -0.10; p <.001) and cross-sectional (WMD: -0.29, 95% CI = -0.44, -0.13, p <.001) studies with high heterogeneity and no publication bias. In subgroup analysis, subjects with cognitive impairment (WMD: -0.87, 95% CI: -1.61, -0.13, p =.000), and age >50 years (WMD: -0.39, 95% CI: -0.74, -0.05, p =.000), had lower sRAGE levels in case-control studies. Also, dementia patients (WMD: -0.41, 95% CI: -0.72, -0.10, p =.014) with age >50 years (WMD: -0.33, 95% CI: -0.54, -0.13, p = 0.000) and in Asian countries (WMD: -0.28, 95% CI: -0.42, -0.13, p =.141) had lower sRAGE levels in cross-sectional studies. CONCLUSION: This meta-analysis revealed a significant reduction in sRAGE in neurocognitive and neuropsychiatric disorders particularly in Asians and moderate age.

Association of dietary insulinaemic potential and odds of non-alcoholic fatty liver disease among adults: A case-control study.

BACKGROUND: Hyperinsulinaemia is considered as a major risk factor for the development of a myriad of chronic diseases. We examined the association between the dietary insulinaemic potential and the odds of non-alcoholic fatty liver disease (NAFLD) among Iranian adults. METHODS: After being subjected to a liver ultrasound, 166 patients with NAFLD and 200 controls were included in the study. The dietary intakes and the physical activity levels of the participants were evaluated using a validated semi-quantitative food frequency questionnaire and the International Physical Activity Questionnaire (short IPAQ), respectively. The insulinaemic potential of the diet was assessed by computing the scores of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and the Empirical Dietary Index for Insulin Resistance (EDIR). RESULTS: Compared with the control subjects, patients with NAFLD were significantly older; had higher values for body mass index, fasting blood sugar, triglycerides, low-density lipoprotein cholesterol, total cholesterol and alanine transaminase; and were more likely to smoke. Moreover, NAFLD patients had significant lower levels of high-density lipoprotein cholesterol and were less likely to perform physical activity. The risk of NAFLD was higher in the individuals in the highest tertile of the EDIH (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.32-5.90; p value for trend < 0.05) and EDIR (OR = 2.42; 95% CI = 1.22-4.79; p value for trend < 0.05) compared to those in the lowest tertile of these scores. CONCLUSIONS: Our study indicates that a higher dietary insulinaemic potential is associated with an increased risk of NAFLD.

Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats.

BACKGROUND: There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats. METHODS AND MATERIALS: Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD + vitamin D, HFD and HFD + vitamin D. Vitamin D was administered at 500 IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods. RESULTS: HFD significantly increased TNF-α (P = 0.04) and NF-κB (P = 0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD + vitamin D group (P = 0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations. CONCLUSION: Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms.

The effects of vitamin D administration on brain inflammatory markers in high fat diet induced obese rats.

BACKGROUND: Obesity induced brain inflammation is associated with cognitive disorders. We aimed to investigate the influence of vitamin D on hypothalamus and hippocampus inflammatory response in high-fat diet induced obese rats. METHODS: In the beginning of the study, 40 rats were divided into two groups: control diet and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: N, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. IL-6, IL-1ß, NF-Kß and acetylcholine (ACH) and brain derived neurotropic factor (BDNF) concentrations in hippocampus and hypothalamus homogenate samples were measured by commercial ELISA kits. RESULTS: Vitamin D administration, reduced food intake and weight gain in studied groups (P < 0.001). Vitamin D reduced hippocampus acetylcholine concentrations in ND + vitamin D group (P < 0.001). High fat diet increased hippocampus IL-6 concentrations significantly (P < 0.05) compared with normal diet receiving groups. Vitamin D could not have significant effects on IL-6 concentrations. Vitamin D administrations reduced IL-1ß, NF-Kß and acetylcholine concentration and BDNF concentrations in ND + vitamin D compared with ND group. These reductions were not significant in HFD + vitamin D versus HFD group. CONCLUSION: According to our results, vitamin D reduced food intake and weight gain and modulated the HFD induced inflammatory response in hippocampus and hypothalamus of high fat diet induced obesity. Therefore, this neurosteroid, can be suggested as a supplemental therapeutic tool in prevention of obesity related cognitive and neurodegenerative problems.

Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats.

BACKGROUND: Obesity is associated with numerous metabolic and inflammatory disorders. The current study was aimed to evaluate the effects of vitamin D administration on the markers of oxidative stress and inflammation in the cardiac tissue of high-fat diet induced obese rats. METHODS: In the beginning of the study, 40 male Wistar rats were divided into two groups: normal diet (ND) and high fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: ND, ND + vitamin D, HFD and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. Tumor necrosis factor (TNF)-α concentration and markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) concentrations in the cardiac tissue and serum concentrations of lipids in rats were determined using ELISA kits and spectrophotometry methods respectively. RESULTS: According to our results, GPx activity in ND and ND + vitamin D group was significantly higher compared with HFD group. Similarly, SOD activity was also significantly increased in ND + vitamin D group compared with ND and HFD groups. Moreover, vitamin D administration, significantly reduced catalase activity in ND + vitamin D and HFD + vitamin D groups (P < 0.05). TNF-α concentration in heart tissue in ND + vitamin D group significantly reduced compared with ND group. Cardiac tissue MDA concentration in baseline or after vitamin D administration did not changed significantly. CONCLUSION: Vitamin D improved cardiac oxidative stress and inflammatory markers in HFD induced obese rats. Further studies in human models are needed to further confirm the use of this nutrient in daily clinical practice.

Association between visceral adiposity and generalized anxiety disorder (GAD).

BACKGROUND AND OBJECTIVES: Due to an increased rate of inflammation in generalized anxiety disorder (GAD), insight into the mediating factors in the onset and recurrence of the inflammatory response can help to achieve novel treatments for alleviating the risk of GAD. In the current study, we aimed to evaluate the possible relationship between visceral adipose tissue (VAT) as an important intermediary in inflammation pathways and GAD in participants of the Employees' Health Cohort Study of Iran (EHCSIR). METHOD: We analyzed the data from 3889 included participants aged > 18 years in the EHCSIR study, which were collected from 2017 to 2020. Lifetime and 12-month GAD were assessed using the Composite International Diagnostic Interview (CIDI-2.1) questionnaire. The adjusted prevalence ratio was computed to evaluate the association between GAD and visceral adiposity index (VAI), GAD and visceral fat area (VFA), GAD and body mass index (BMI) and ultimately GAD and waist circumference (WC) in males and females using STATA software. RESULTS: Log-binomial analysis showed a higher prevalence ratio of 12-month GAD associated with VFA in women [PR: 1.42, CI: 1.07-1.87, P: 0.015]. The prevalence of lifetime GAD was higher in obese women (BM1 > 30) [PR: 2.35, CI: 1.07-5.13, P:0.03] than in women with normal BMI. Women with higher VAI were also significantly more likely to suffer lifetime GAD [PR: 1.25, CI: 1.05]. 1.48, P:0.01]. In males, the prevalence of lifetime diagnosed GAD per 1 standard deviation increase in VFA was 0.65 [CI: 0.46-0.91, P: 0.01]. CONCLUSION: Visceral adiposity as a positive agent was associated with GAD prevalence in women. The presence of GAD symptoms showed no relationship to VFA in men.

Effect of cardamom supplementation on a number of metabolic factors: A systematic review and meta-analysis.

BACKGROUND & AIMS: Cardamom known as "queen of spice" seems to be an anti-diabetic agent due to its poly phenolic content. Since, recent studies reported controversial results related to its effect on metabolic factors, present meta-analysis examined the effect of cardamom supplementation on glycemic indices and weight profile of randomized controlled clinical trials (RCTs). METHODS: A wide search was done on biomedical electronic databases including Scopus, PubMed, Cochrane, EMBASE and Iranian databases, for all relevant literature published up to May 2021. Our search strategy included: [HbA1C, Blood Sugar, glycemic index, glucose tolerance test, insulin, insulin resistance, insulin sensitivity, body weight, BMI, body composition, waist circumferences] added to searched queries based on scientific Mesh terms. The included papers required to be RCTs that reported the effect of cardamom on glycemic and weight indices. We excluded studies with: a) non-randomized or non-controlled trials, b) animal studies, c) not available full text articles d) duplicate citations and e) not available full text articles. The risk of bias was assessed based on the Cochrane Risk of Bias tool. The effects of cardamom supplementation were assessed using standardized mean difference (SMD) statistics. The SMD of metabolic risk factors were pooled together using random effect meta-analysis method. RESULTS: Totally, six publications enrolling 410 participants was included in present meta-analysis. Daily 3 g supplementation of cardamom from 8 weeks to 3 months showed no significant effect on BMI (WMD: 0.07; 95% CI: [-0.12, 0.27]; P:0.5), weight (WMD: 0.01; 95% CI: [-0.22, 0.21]; P:0.95) and WC (WMD: 0.09; 95% CI: [-0.34, 0.17]; P:0.63), FBS (WMD: 0.10; 95% CI: [ -0.32, 0.12]; P:0.37), insulin (WMD: 0.83; 95% CI: [-2.07, 0.40]; P:0.19) and QUICKI (WMD: 1.14; 95% CI: [-1.11, 3.39]; P:0.32). However, significant effect occurred on HOMA-IR (WMD: 0.40; 95% CI: [-0.65, -0.15]; P:0.00), and HbA1C (WMD: 0.48; 95% CI: [-0.80, -0.16]; P:0.00). CONCLUSION: Final findings suggest ameliorative effect of cardamom on metabolism of glucose.

Effects of cashew nut consumption on body composition and glycemic indices: A meta-analysis and systematic review of randomized controlled trials.

BACKGROUND AND AIMS: Present meta-analysis and systematic review was conducted to synthesis a definitive conclusion from previous randomized controlled clinical trials (RCTs). METHODS: A comprehensive search was done up to July 2020, in order to extract RCTs which investigated the effect of cashew nut on weight, body mass index (BMI), waist circumference (WC), fasting blood sugar (FBS), insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate effect size. Meta regression analysis was done to identify probable sources of heterogeneity. RESULTS: Six clinical trials with 521 participants were included. Combined effect sizes demonstrated no effect of cashew consumption on weight (WMD): 0.02, 95% CI: -1.04, 1.09, P > 0.05), BMI (WMD: 0.1, 95% CI: -0.72, 0.74, P > 0.05), and WC (WMD: -0.13, 95% CI: -1.97, 1.70, P > 0.05). Results were also not significant for FBS (WMD: 3.58, 95% CI: -3.92, 11.08, P > 0.05), insulin (WMD: -0.19, 95% CI: -1.63, 1.25, P > 0.05), and HOMA-IR (WMD: 0.25, 95% CI: -0.55, 1.06, P > 0.05). CONCLUSION: The sum up, incorporating cashew into the diet has no significant effect on body composition or modifying glycemic indices.

Adipose Tissue Inflammation and Oxidative Stress: the Ameliorative Effects of Vitamin D.

Obesity is a low-grade inflammatory disease and is associated with numerous comorbidities. The current study was aimed to evaluate the effects of vitamin D administrations on markers of inflammation and oxidative stress in adipose tissue of high-fat diet-induced obese rats. In the beginning of the study, 40 rats were divided into two groups: normal diet and high-fat diet (HFD) for 16 weeks; then, each group was subdivided into two groups including ND, ND + vitamin D, HFD, and HFD + vitamin D. Vitamin D supplementation was done for 5 weeks at 500 IU/kg dosage. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-ß and IL-6 concentrations and markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) concentrations in adipose tissue of rats were determined using ELISA kits and spectrophotometry methods, respectively. Vitamin D treatment led to a significant reduction in adipose tissue TNF-α concentrations in both ND + vitamin D and HFD + vitamin D groups (P < 0.05). Adipose tissue MCP-1 concentration also reduced in HFD + vitamin D group compared with HFD group. Among markers of oxidative stress in adipose tissue, SOD and GPx concentrations significantly increased in adipose tissue of HFD + vitamin D treated group compared with other groups (P < 0.05). Reduced food intake and weight gain was also occurred after vitamin D treatment. Vitamin D improved adipose tissue oxidative stress and inflammatory parameters in obese rats. Vitamin D treatment was also associated with decreased food intake and decreased weight gain in animals under a high-fat diet. Further studies are needed to better clarify the underlying mechanisms.

Insulin deficiency: A possible link between obesity and cognitive function.

BACKGROUND: Epidemiological studies proposed a linear connection between developing dementia including Alzheimer's disease (AD) and obesity. Adiposity, insulin resistance and dementia indicated probable mechanistic links in this process. Indeed, it has been known that optimum insulin action in the brain plays critical role in cognitive function; whereas, insulin resistance in obese individuals finally leads to insulin deficiency in central nervous system (CNS) and down regulation of the efficiency of insulin uptake from periphery into CSF. In the current study, we aimed to assess correlation between increased body weight and insulin resistance with CSF to serum ratio of insulin and to evaluate the correlation between CSF to serum ratio of insulin with cognitive function in high fat diet induced obese rats. METHODS AND MATERIAL: Twelve male Wister rats were randomly divided into two groups receiving Diet 1 (D1, 10% fat) and Diet 2 (D2, 59% fat) for 16 weeks. Weight was recorded weekly to assure body weight gain. Morris Water Maze (MWM) task was designed to assess spatial learning memory function. Finally, blood samples were collected for determining fasting serum glucose using enzymatic spectrophotometric method, insulin levels by ELISA kit and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Fasting Cerebrospinal Fluid (CSF) insulin was also measured by ELISA kit. RESULT: D1 and D 2 groups both experienced weight gain but weight gain in D2 group were significantly higher. A significant correlation between CSF to serum ratio of insulin with weight (r=0.882, p=0.001) and HOMA-IR index (r=0.798, p=0.002) was reported. Moreover, the present study indicated significant correlations between CSF to serum ratio of insulin and escape latency time in first (r=0.631, p=0.028), second (r=0.716, p=0.009) and third (r=0.609, p=0.036) day of MWM test and probe time of MWM test (r=0.762, p=0.004). CONCLUSION: Increased body weight induced by high fat diet and insulin resistance in rats led to down regulation of CSF to serum ratio of insulin in the current research. Brain insulin deficiency may be responsible for possible decline of cognitive function in obesity. More researches are needed to better clarify the underlying mechanisms and also to confirm the similar findings in human studies.

The Impact of Vitamin D Supplementation on Neurodegeneration, TNF-α Concentration in Hypothalamus, and CSF-to-Plasma Ratio of Insulin in High-Fat-Diet-Induced Obese Rats.

There is growing evidence that obesity can lead to neurodegeneration induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF-α). Moreover, obesity is associated with reduced transport of insulin through the blood-brain barrier (BBB). Insulin deficiency in the brain especially in the hypothalamus region has neurodegenerative and obesity-promoting effects. Because of the anti-inflammatory and neuroprotective effects of vitamin D, in the current experimental study, we aimed to investigate the effects of vitamin D supplementation on neurodegeneration, TNF-α concentration in the hypothalamus, and cerebrospinal fluid (CSF) to serum ratio of insulin in high-fat-diet-induced obese rats. At the first phase of the study, the rats were divided into two groups: (1) normal diet (ND, 10% fat) and (2) high-fat diet (HFD, 59% fat) and were fed for 16 weeks. In the second phase, each group was subdivided into four groups including the following: ND, normal diet + vitamin D, HFD, and HFD + vitamin D. Weight was measured and recorded weekly. Vitamin D supplementation for 5 weeks at 500 IU/kg dosage was used. One week after vitamin D supplementation, daily food intake was recorded. At week 22, blood was collected to determine fasting serum glucose, vitamin D, and insulin concentrations, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. CSF samples were also collected to measure insulin concentrations, and the hypothalamus was dissected to determine TNF-α concentration. HFD significantly increased TNF-α concentrations and degenerated neurons in the hypothalamus (P = 0.02). We also observed a significant reduction of CSF-to-serum ratio of insulin in HFD group (P = 0.03). The HOMA-IR test indicated significant increment of insulin resistance in HFD-fed rats (P = 0.006). Vitamin D supplementation in HFD group significantly reduced weight (P = 0.001) and food intake (P = 0.008) and increased CSF-to-serum ratio of insulin (P = 0.01). Furthermore, vitamin D decreased insulin resistance in the HFD group (P = 0.008). Vitamin D had no significant effect on degenerated neurons and TNF-α concentration in the hypothalamus. According to our findings, vitamin D improved brain insulin homeostasis and modulated food intake and body weight in high-fat-diet-induced obese rats. Further studies are needed to better clarify the underlying mechanisms.