👤 Hamed Mirzaei

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric impairments, partly due to disruptions in neurotrophin signaling. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) play critical roles in neuronal survival, synaptic plasticity, and neuroprotection, yet their alterations across biofluids and brain regions in HD remain unclear. This study systematically reviewed and meta-analyzed human and rodent studies to quantify neurotrophin changes and explore moderating factors. Comprehensive searches of PubMed, Scopus, Web of Science, Embase, Google Scholar, and clinical trial registries were conducted up to December 2025. Studies reporting measurable BDNF, NGF, or NT-3 levels in HD patients or animal models were included. Data were extracted on neurotrophin type, sample source, subject characteristics, and measurement methods. Standardized mean differences were calculated using random-effects models, and meta-regression was applied to evaluate the effects of species, sex, sampling region, and analytical techniques. The results showed a significant decrease in neurotrophin levels in both peripheral biofluids and central brain regions in HD. The results for moderator analyses showed that species and sex significantly affected the magnitude of changes in ELISA-based studies, whereas molecular methods consistently detected reductions irrespective of these factors. No significant publication bias was identified. These findings highlight significant neurotrophic deficits in HD, highlight the importance of biological and methodological considerations in interpreting neurotrophin data, and suggest that peripheral neurotrophin measurements may serve as accessible biomarkers for disease progression. Show less

Prenatal stress is a significant risk factor that can lead to neurobehavioral deficits in offspring. In the present study, we examined the effects of a probiotic mixture on anxiety, memory, and underlying possible molecular pathways in prenatally stressed rats. Male offspring exposed to chronic unpredictable stress (CUS) during fetal life were received either saline (CUS+SAL) or a probiotic mixture (CUS+PRO) for 30 days post-weaning. Non-stressed controls were also given either saline (CON+SAL) or probiotics (CON+PRO). The passive avoidance test and the elevated zero maze test were used to assess avoidance memory and anxiety-like behavior, respectively. In comparison to the CON+SAL controls, the CUS+SAL group exhibited significant anxiety-like behavior and impaired avoidance memory. At a molecular level, the behavioral impairments were accompanied by increased serum levels of the oxidant, MDA, and decreased serum levels of antioxidants, TAC, GSH, and SOD, upregulation of the hippocampal serotonin receptor Htr1a gene, while downregulation of microRNAs miR-26a and miR-320-3p, reduced BDNF, and increased Bax/Bcl-2 ratio apoptosis in the duodenum. Probiotics effectively mitigated these alterations. The intervention improved behavioral functions, normalized oxidative and antioxidative stress markers, and restored the expression of Htr1a and miR-320-3p to near-normal levels, while miR-26a expression remained unaffected by the treatment. It also enhanced the Bax/Bcl-2 ratio and increased BDNF content. Interestingly, unstressed control rats were unresponsive to the probiotic treatment. Conclusively, probiotic supplementation sufficiently alleviates the adverse effects of fetal life stress, possibly by affecting the gut-brain axis, highlighting the importance of beneficial bacteria in neurobehavioral development and maintenance. Show less

Depression is a widespread neuropsychiatric disorder that significantly impacts emotional and cognitive function. Antidepressant medications are frequently accompanied by various adverse effects. C-phycocyanin has been previously shown to exert potent anti-inflammatory, and neuroprotective properties. Therefore, this study evaluated the therapeutic effects of C-phycocyanin against anxiety and depressive-like behaviors, and memory dysfunction in an animal model of chronic unpredictable mild stress (CUMS)-induced depression and explored the underlying mechanisms. Rats were daily exposed for six weeks to CUMS, during which phycocyanin (100 mg/kg, orally) was administered in the final three weeks of the study. Following the assessment of anxiety/ depressive-like behaviors, and memory dysfunction by the open field test (OFT), tail suspension test (TST), elevated plus maze (EPM), and passive avoidance test (PAT), rats were euthanized by decapitation. Then, hippocampal TNF-α and IL-1β concentrations, and hippocampal protein expressions (Iba-1, CD86, NF-κβ, CREB, and BDNF) were determined by an ELISA assay, and western blots, respectively. C-phycocyanin significantly decreased immobility time in OFT and TST, increased open arm time in EPM, and step-through latency time in PAT. Furthermore, C-phycocyanin suppressed CUMS-induced the M1 microglia polarization and neuroinflammation by reducing hippocampal TNF-α and IL-1β concentrations, and the protein expression of Iba-1, CD86, and NF-κβ in the hippocampus of CUMS-exposed rats. It also increased the hippocampal protein expression of CREB and BDNF. C-phycocyanin improved CUMS-induced anxiety and depressive-like behaviors, and memory dysfunction, which could be explained, at least in part, by inhibition of M1 microglial polarization and neuroinflammation, and enhancement of CREB/BDNF signaling. Show less

This study, for the first time, sought to investigate whether the interaction between the GRS consists of three SNPs (CAV-1, CRY-1, MC4R) and fat intake is associated with inflammatory markers among Iranian overweight and obese women. This cross-sectional study was conducted with 246 overweight and obese women, aged 18-48 years. Three SNPs, including CAV-1 rs3807992, CRY-1 rs2287161, and MC4R rs17782313, were genotyped using PCR-RFLP to calculate the genetic risk score (GRS) for each participant. Dietary fat intake was measured using a validated semi-quantitative food frequency questionnaire (FFQ). C-reactive protein (CRP), interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and Galectin-3 (Gal-3) were assessed as the primary outcomes of the study. After controlling for confounding variables, a significant interaction between high total fat intake and high GRS, compared to the reference group, was found for TGF-β level ( Consuming different types of fats can influence the interaction between GRS and inflammatory markers, suggesting further research is needed to fully understand this relationship. The online version contains supplementary material available at 10.1007/s40200-024-01542-z. Show less

Recent studies suggest a link between dietary fat quality and obesity. Genetic risk scores (GRS) can predict obesity risk based on genetic factors. This study investigates how GRS and fatty acid quality affect visceral adiposity index (VAI) and body adiposity index (BAI) in overweight and obese women. In this study, 278 overweight and obese women (aged 18-58) participated. We have used a comprehensive food frequency questionnaire (FFQ) to evaluate dietary intake and the fatty acids quality indexes. We have employed standard methods to measure biochemical factors, anthropometrics, and physical activity levels. Finally, the GRS was created by combining three SNPs [CAV-1 (rs3807992), Cry-1 (rs2287161), and MC4R (rs17782313)]. The study found that there was no significant association between the quality of fat intake (as measured by CSI score and N6/N3 score) and VAI or BAI in both crude (B = 70.70, SE = 35.14, CI:1.81-139.55, P = 0.04) and adjusted models (B = 93.67, SE = 39.28, CI:16.68-17.68, P = 0.01). CSI provides information on cholesterol and saturated fats. However, there was a notable interaction between the GRS and the N6/N3 score on VAI, suggesting that obese women with high obesity-related SNPs who consumed foods with a higher ratio of N6/N3 fatty acids tended to have an increased VAI. This study shows; that eating more food sources containing a higher ratio of N6/N3 may be the reason for the increase in VAI in obese women who have high obesity-related SNPs and emphasizes the matter of personalized nutrition in obesity issues. Show less

The growth in obesity and rates of abdominal obesity in developing countries is due to the dietary transition, meaning a shift from traditional, fiber-rich diets to Westernized diets high in processed foods, sugars, and unhealthy fats. Environmental changes, such as improving the quality of dietary fat consumed, may be useful in preventing or mitigating the obesity or unhealthy obesity phenotype in individuals with a genetic predisposition, although this has not yet been confirmed. Therefore, in this study, we investigated how dietary fat quality indices with metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) based on the Karelis criterion interact with genetic susceptibility in Iranian female adults. In the current cross-sectional study, 279 women with overweight or obesity participated. Dietary intake was assessed using a 147-item food frequency questionnaire and dietary fat quality was assessed using the cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (N6/N3) essential fatty acids. Three single nucleotide polymorphisms-MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1(rs2287161) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and were combined to produce the genetic risk score (GRS). Body composition was evaluated using a multi-frequency bioelectrical impedance analyzer. Participants were divided into MHO or MUO phenotypes after the metabolic risk assessment based on the Karelis criteria. We found significant interactions between GRS and N6/N3 in the adjusted model controlling for confounding factors (age, body mass index, energy, and physical activity) (β = 2.26, 95% CI: 0.008 to 4.52, P = 0.049). In addition, we discovered marginally significant interactions between GRS and N6/N3 in crude (β = 1.92, 95% CI: -0.06 to 3.91, P = 0.058) and adjusted (age and energy) (β = 2.00, 95% CI: -0.05 to 4.05, P = 0.057) models on the MUH obesity phenotype. However, no significant interactions between GRS and CSI were shown in both crude and adjusted models. This study highlights the importance of personalized nutrition and recommends further study of widely varying fat intake based on the findings on gene-N6/N3 PUFA interactions. Show less

There is a lack of comprehensive understanding concerning the variations in cardiometabolic parameters due to the interactions between dietary habits and Lipoprotein lipase (LPL) gene polymorphisms. This study aimed to investigate how primary dietary patterns relate to the Rs320 variant of the LPL gene and their impact on the cardiometabolic profile in a group of Iranian adults. This cross-sectional study involved 387 adults in Yazd, Iran, ranging in age from 20 to 70. Following an assessment of the inclusion and exclusion criteria, participants in the Yazd Health Study (YaHS) enrollment phase were chosen. In the present study, the major dietary patterns were identified using factor analysis method. The polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method was used to identify rs320 variant on LPL gene. General linear models (GLM) were applied to evaluate how dietary patterns interact with rs320 polymorphism to influence cardiometabolic markers. Three major dietary patterns were identified: western, healthy, and traditional. The allele distributions of rs320 were 66.5% for T and 33.5% for G. The prevalences of the genotypes were 57.90% ( The online version contains supplementary material available at 10.1038/s41598-025-27399-7. Show less

Cardiovascular disease (CVD), which is an important global health challenge, is expanding. One of the main factors in the occurrence of CVD is a high genetic risk. The interaction between genetic risk in CVD and nutrition is debatable. Polyphenols are one of the important dietary components that may have a protective role in people who have a high genetic risk score (GRS) for cardiometabolic risk factors. This study, conducted in overweight and obese women, examines the interaction between polyphenol intake and specific genes (MC4r, Cav-1, and Cry1) related to maintaining body balance and their interaction with cardiometabolic risk factors. This cross-sectional study included 391 women who were overweight or obese, aged 18 to 48 years, with a body mass index (BMI) between 25 and 40 kg/m The mean ± standard deviation (SD) age and BMI of women were 36.67 (9.1) years and 30.98 (3.9) kg/m According to our findings, those with a high GRS may have a protective effect on cardiometabolic risk factors by consuming high amounts of polyphenols. Further studies will be necessary in the future to validate this association. Show less

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study. Show less

Obesity has become a common global problem. Some obese people can be metabolically healthy. Gene-environment interaction can be important in this context. This study aimed to assess the interaction between dietary fat quality indices and the Melanocortin 4 receptor (MC4R) gene in metabolically healthy and unhealthy overweight and obese women. This cross-sectional study was conducted on 279 women with overweight and obesity. The definition of metabolically healthy and unhealthy phenotypes was done according to Karelis criteria. Dietary assessment was done using a 147-item validated semi-quantitative food frequency questionnaire and dietary fat quality was assessed by cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (N6/N3) essential fatty acids. MC4R was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. A generalized linear model was used to evaluate the interaction between dietary fat quality indices and the MC4R gene in both crude and adjusted models. Study subjects with higher ratio of N6/N3 had higher homeostatic model assessment for insulin resistance (HOMA IR) index (P = 0.03) and other variables showed no difference according to the tertile of CSI and N6/N3. Participants with the C allele of MC4R rs17782313 had lower height (P < 0.001) and higher HOMA index (P = 0.01). We found that the CC genotype of MC4R interacts with the N6/N3 ratio on the metabolically unhealthy phenotype in the crude model (β = 9.94, CI 2.49-17.39, P = 0.009) and even after adjustment for all confounders (β = 9.002, CI 1.15-16.85, P = 0.02, β =  - 12.12, CI 2.79-21.46, P = 0.01). The data of this study can justify one inconsistency observed in society, regarding dietary recommendations about metabolic health status. Those with CC genotype, are more likely to have an unhealthy phenotype with an increase in N6/N3 as one fat quality indices than those who do not have CC genotype. We found the interaction of dietary fat quality indices such as N6/N3 and the MC4R gene in metabolically unhealthy overweight and obese women. Show less

The aim of this study is to investigate the interaction of fatty acid quality indices and genes related to lipid homeostasis on mental health among overweight and obese women. This cross-sectional study included 279 overweight and obese women for N6/N3 ratio and 378 overweight and obese women for CSI aged 18-58 years. Mental health were evaluated using Depression Anxiety Stress Scales (DASS-21). The anthropometric indices, biochemical parameters, body composition and dietary fat quality were measured. MC4R (rs17782313) and Caveolin-1 (CAV-1) (rs3807992) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results of the study showed that after adjusting for age, energy intake, thyroid disease, physical activity, and BMI, a positive interaction between TC genotype of MC4R and CSI on depression (β = 0.39, CI = 0.12, 0.66, P = 0.004), and DASS-21 (β = 0.074, CI = 0.04, 1.44, P = 0.036). Also, there were a marginal significant interactions between AG genotype of CAV-1 and N6/N3 ratio on depression in adjustment model1 (β = 16.83, CI = - 0.19, 33.85, P = 0.053). Our findings showed that increasing adherence to fatty acid quality indices by considering genes related to lipid homeostasis was related to increasing depression in our population. Show less

Previous studies have shown that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313 may be associated with depressed mood. Moreover, dietary patterns have potentially adverse effects on depression. This study investigates the interactions between the MC4R gene variant (rs17782313) and dietary patterns on depression among Iranian obese and overweight women. A total of 289 Iranian overweight and obese women, aged 18-50 years, were enrolled in this cross-sectional study. Biochemical, anthropometric, and body composition indices were assessed in all participants. Moreover, MC4R rs17782313, by the restriction fragment length polymorphism (PCR-RFLP) method, and depression, using the 21-item Depression Anxiety Stress Scales (DASS) questionnaire, were assessed. Food intakes were assessed by completing a 147-item semi-quantitative food frequency questionnaire (FFQ). By the use of factor analysis, 2 major dietary patterns were extracted: healthy dietary pattern (HDP) and unhealthy dietary pattern (UDP). Binary logistic analysis showed that individuals with minor allele risk (CC) with high adherence to the unhealthy pattern increased odds for depression (OR: 8.77, 95%CI: -0.86-18.40, P: 0.07), after controlling for confounders. Also, a logical inverse relationship was observed between CT genotype and HDP on depression in the crude and adjusted models (OR: -0.56, 95% CI: -3.69-2.57, P: 0.72) (OR: -4.17, 95% CI: -9.28-0.94, P: 0.11), although this interaction was not statistically significant. According to the above findings, adherence to unhealthy food intake pattern increases odds of depression in MC4R risk allele (C allele) carriers. To confirm these findings, more studies are needed in the form of clinical trials and prospective studies with higher sample sizes. Show less

Mental health and sleep quality are associated with genetics and nutrient and energy intake. The present study examined the association between ultra-processed food (UPF) intake and genetic risk score (GRS) and their interactions on mental health and sleep quality in Iranian women. A cross-sectional study was conducted on 278 overweight and obese females aged between 18 and 56 years. According to the NOVA classification system, 37 food groups and beverages were collected using a 147-item semi-quantitative food frequency questionnaire (FFQ). The blood parameters of all participants were assessed. Mini-column kit (type G; Genall; Exgene) and the PCR-RFLP method were used to extract DNA and determine gene polymorphism, respectively. Three single nucleotide polymorphisms (SNPs), including Caveolin₁ (Cav₁₎, Melanocortin4 receptor (MC4R), and cryptochrome circadian regulator 1 (CRY1), were used to calculate GRS. The individual risk allele (0, 1, 2) for each SNP was calculated using the incremental genetic model. After controlling for confounders, a significant interaction was found for depression (β = 0.026, 95% CI 0.003, 0.049, P = 0.028) and depression anxiety stress scales (DASS) score (β = 0.059, 95% CI 0.001, 0.117, P = 0.046) on the NOVA classification system and GRS. The findings of this study showed a significant interaction between GRS and the NOVA classification system on mental disorders, including depression, DASS score and stress. There was also a significant relationship between the NOVA classification system and anxiety, DASS score, sleep quality and depression. Furthermore, a partially significant association was observed between GRS and stress. Level V, cross-sectional descriptive study. Show less

For more than eight decades, cardiovascular disease (CVD) has remained the leading cause of death in the world. CVD risk factors are multifaceted, with genetics and lifestyle both playing a role. The aim of this study was to investigate the association between a genetic profile risk score for obesity GRS and cardio-metabolic risk factors in overweight and obese women. The current cross-sectional study was conducted on 391 overweight and obese women. The genetic risk score was created by combining three single nucleotide polymorphisms [MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161)]. Anthropometric measurements, blood pressure, and some blood parameters were measured by standard protocols. A significant association between the GRS and some of cardiometabolic risk factors variables such as body mass index (β = 0. 49, 95%CI = 0.22 to 0.76, p < 0.001), waist circumference (β = 0. 86, 95%CI = 0.18 to 1.54, p = 0.01), body fat mass (β = 0. 82, 95%CI = 0.25 to 1.39, p = 0.005), %body fat (β = 0. 44, 95%CI = 0.06 to 0.82, p = 0.02), and hs-CRP (β = 0.46, 95% CI = 0.14 to 0.78, p = 0.005) was observed in crude model. After adjustment for confounding factors (age, BMI, and physical activity), a significant positive association was observed between BMI (p = 0.004), WC (p = 0.02), body fat mass (p = 0.01), %BF (p = 0.01), hs-CRP (p = 0.009), and GRS. In addition, we discovered a significant negative association between the GRS and BMC (= -0.02, 95%CI = -0.05 to -0.001, p = 0.04). But other variables did not show any significant association with GRS among obese and overweight women. We found a significant positive association between GRS, including MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161) and cardiometabolic risk factors among overweight and obese Iranian women. Show less

Cardiovascular disease (CVD) is the leading cause of death in women globally. Recent studies have reported that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313 may be related to the incidence of obesity and the risk of CVD. Therefore, the present study aimed to investigate the interactions between the modified Nordic-style diet score (MND) and MC4R gene variant on markers of CVD. The current cross-sectional study was conducted on 282 Iranian women, aged 18-48 years, with a body mass index (BMI) ≥ 25. MND score was assessed using a 147 items food frequency questionnaire (FFQ). Genotyping of the MC4R (rs17782313) was conducted by the PCR method. The anthropometric measurements and serum profiles were assessed by standard protocols. The means and standard deviation (SD) of age, weight, and BMI of individuals were 36.67 ± 9.10 years, 81.29 ± 12.43 kg, and 31.26 ± 4.29 kg/m In conclusion, the results of the present study suggest that diet, gene variants, and their interaction should be considered in metabolic disease risk assessment. Further studies are needed to confirm these data and better elucidate the interaction. Show less

The current prevalence of the metabolically healthy obesity is about 3%. Genetic and nutrition are influencers of such phenotypes. The main goal of this study was to assess the interaction between Dietary Total Antioxidant Capacity (DTAC) and the genotypes of MC4R and Insulin resistance in metabolically healthy/unhealthy overweight and obese women in Iran. This cross-sectional study was conducted on 237 overweight-obese women with a mean age of 36. The value of Dietary total antioxidant capacity (DTAC) was calculated using the following indices: Total reactive antioxidant potential (TRAP), Trolox equivalent antioxidant capacity (TEAC), and ferric reducing ability of plasma (FRAP). The Metabolic health status was evaluated using the Karelis criteria. Melanocortin 4 receptor single nucleotide polymorphisms were determined by the restriction fragment length polymorphism (PCR-RFLP) method. Also, insulin resistance was evaluated through homeostasis model assessment (HOMA). Our data noted that 72.96% of participants presented Unhealthy Metabolically and 26.94% Healthy Metabolically including 33.5% of the total had T/T genotype, 23.8% had the C/T genotype, and 42.5% had the C/C genotype ( The findings indicated that there are significant associations between genotypes of rs1333048 SNP and DTAC. The C/C genotype subjects with higher DTAC had a better lipid profile and were metabolically healthier. Show less

Previous studies have shown that the C allele of melanocortin 4 receptor (MC4R) rs17782313 and the Alternative Healthy Eating Index (AHEI) are separately associated with obesity. However, the present study aimed to investigate the interaction between MC4R rs17782313 variants and the AHEI and their association with central and general obesity indices, which has not been assessed previously. In total, 291 women with body mass index (BMI) ≥ 25 kg m After adjustment for age, energy intake, physical activity, marital status, and economic status, the interaction between MC4R rs17782313 and the AHEI was associated with hip circumference [β = -0.41, 95% confidence interval (CI) = -0.77 to -0.05, p = 0.02], BMI (β = -0.15, 95% CI = -0.29 to -0.02, p = 0.02), fat mass (kg) (β = -0.28, 95% CI = -0.56 to -0.01, p = 0.03), visceral fat area (β = -5.68, 95% CI = -9.55 to -1.80, p = 0.004). The other measures that appear to be suggestively related to this interaction (0.05 < p < 0.07) are waist circumference, waist-to-height ratio, trunk fat (%), trunk fat (kg), fat mass (%) and fat mass index. The interaction between MC4R rs17782313 and the AHEI can be related to central and general obesity indices in overweight/obese women. Show less

Recent studies have shown that dietary carbohydrate quantity and quality as well as genetic variants may contribute to determining the metabolic rate and general and central obesity. This study aimed to examine interactions between melanocortin 4 receptor gene (MC4R) rs17782313 and dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) on body mass index (BMI), waist circumferences (WC), basal metabolic rate (BMR), and BMR/kg in overweight/obese women. A total of 282 Iranian women (BMI ≥ 25) aged 18-56 years were enrolled in this cross-sectional study. All participants were assessed for blood parameters, body composition, BMR, and dietary intake. Dietary carbohydrate intake, GI, and GL were determined using a valid, reliable 147-item food frequency questionnaire. MC4R rs17782313 was genotyped by the restriction fragment length polymorphism (PCR-RFLP) method. After adjustment for age and energy intake, significant interactions were observed between carbohydrate intake and MC4R rs17782313 in terms of BMI (P Interaction = 0.007), WC (P Interaction = 0.02), and BMR/kg (P Interaction = 0.003) in this way that higher carbohydrate intake, compared with lower intake, was associated with an increase in BMI and WC for individuals with C allele carriers (TC + CC genotypes), while related to an increase in BMR/kg for those carrying the TT genotype. No significant interaction was found between MC4R rs17782313 and GI and GL on BMI, WC, BMR/kg, and BMR. Interactions between the MC4R rs17782313 and carbohydrate intake probably can have an effect on BMI, WC, and BMR/kg in overweight/obese women. Show less

Obesity is one of the risk factors concerns of colorectal cancer (CRC), the most common type of gastrointestinal cancer, due to the changing lifestyle and especially diet. There are various molecular pathways associated with obesity and the risk of CRC incidence, such as insulin resistance or elevated plasma free fatty acids, which alter the signaling pathways of intestinal epithelial cells. The aim of this study was to better understand the significance of unsaturated fatty acid biosynthesis on pathogenesis of colon cancer in obese. Based on GSE20931 dataset, obese individuals affected by CRC had higher increased gene expression than non-obese individuals. The analysis showed that in obese individuals, the 16 signaling pathway genes were activated and increased (FDR <0.05) significantly. The biosynthetic pathway of unsaturated fatty acids showed a cross-talk with the arachidonic acid metabolism pathway and the PPAR signaling pathway is influenced and regulated via these pathways. The biosynthetic pathway of unsaturated fatty acids consisting of 22 genes, were analyzed using GEO data and revealed that 4 genes (HSD17B12, TECR, FADS2, ELOVL5) from this pathway were significantly increased (FDR <0.05). These data were validated based on TCGA data (Adj.p.value <0.001). The expression level of candidate genes in HT-29 cells decreased significantly (P.value <0.01), and PPARγ expression increased under linoleic acid treatment (200 μM) compared to control cells. Moreover, in presence of linoleic acid treatment, migration, colony formation, and proliferation decreased (P.value <0.01) in presence of treatment. In summary, the Biosynthesis pathway of unsaturated fatty acids is an interesting and critical pathway in CRC. Show less

Previous studies have shown that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313, may be associated with incidence of obesity and the risk of cardiovascular diseases (CVDs). Moreover, inflammation caused by the diet has been shown to have, potentially, unfavorable effects on CVD risk. This study used a linear regression model to investigate the interactions between the dietary inflammatory index (DII) and MC4R gene variants on markers of CVD. This comparative cross-sectional study was conducted on 266 Iranian women with overweight and obesity. A food frequency questionnaire (FFQ) with 147 items was used to assess dietary intakes. Individuals were categorized into three groups based on rs17782313 genotype. Participants were also divided into four groups based on DII score. Higher quartiles of DII were associated with lower levels of high density lipoproteins (HDL) (p = 0.01) and higher levels of triglycerides (TG) (p = 0.04). There was a significant difference between genotypes for insulin (p < 0.001), HOMA index (p < 0.001), total body mineral content (p = 0.03), and bone mineral content (BMC) (p = 0.04). Our findings also showed significant interactions between DII score and rs17782313 polymorphism on total cholesterol, total body mineral content, BMC, soft lean mass (SLM), fat free mass (FFM) (p = 0.03), skeletal muscle mass (SMM), and basal metabolic rate (BMR). Higher DII scores were associated with lower HDL levels and higher TG levels, respectively; whilst significant differences were observed between the genotypes of rs17782313 for insulin and HOMA index, total body mineral content, and BMC. These results highlight that dietary compositions, gene variants, and their interaction, should be considered in CVD risk assessment. Show less

Patients with ulcerative colitis (UC) have an increased risk for developing colorectal cancer. Because UC tumorigenesis is associated with genomic field defects that can extend throughout the entire colon, including the non-dysplastic mucosa; we hypothesized that the same field defect will include abnormally expressed proteins. Here we applied proteomics to study the protein expression of UC neoplastic progression. The protein profiles of colonic epithelium were compared from 1) UC patients without dysplasia (non-progressors); 2) none-dysplastic colonic tissue from UC patient with high-grade dysplasia or cancer (progressors); 3) high-grade dysplastic tissue from UC progressors and 4) normal colon. We identified protein differential expression associated with UC neoplastic progression. Proteins relating to mitochondria, oxidative activity, calcium-binding proteins were some of interesting classes of these proteins. Network analysis discovered that Sp1 and c-myc proteins may play roles in UC early and late stages of neoplastic progression, respectively. Two over-expressed proteins in the non-dysplastic tissue of UC progressors, CPS1 and S100P, were further confirmed by IHC analysis. Our study provides insight into the molecular events associated with UC neoplastic progression, which could be exploited for the development of protein biomarkers in fields of non-dysplastic mucosa that identify a patient's risk for UC dysplasia. Show less