مجله غدد درون ریز و متابولیسم ایران
سال بیست و پنجم شماره 2 (پیاپی 128، خرداد و تیر 1402)

Impaired endometrial receptivity and implantation failure have been reported in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying impaired implantation in women with PCOS remain unclear. In this study, the relative expression of the CYP19 gene in ovarian granulosa cells (GCs), as well as SOCS3, HOXA9, and HOXA11 genes in the uterine tissue (genes involved in the implantation process) were examined in the adult rat model of PCOS compared to controls.

Five milligrams of free testosterone was subcutaneously injected into pregnant rats on the 20th day of pregnancy, and pregnant rats in the other group only received solvent. Female offspring who were exposed to androgen during their fetal life were considered as a rat model of PCOS, and female offspring from the other group were considered as the control group (n=8 in each group). The relative expression of the CYP19 gene in ovarian GCs and SOCS3, HOXA9, and HOXA11 genes in the uterus were measured using SYBR-Green real-time PCR.

A significant decrease in the relative expression of the CYP19 gene was observed in the ovarian GCs of the rat model of PCOS compared to controls (p=0.02). In addition, the relative expression of SOCS3 (p<0/001), HOXA9 (p=0.018), and HOXA11 (p=0.007) genes significantly decreased in the uterine tissue of PCOS rats compared to the controls.

Reduced expression of the CYP19 gene in ovarian GCs, SOCS3, HOXA9, and HOXA11 in the uterine tissue may be one of the molecular mechanisms underlying implantation failure in PCOS subjects.

There is still debate regarding the association between dietary saturated fatty acids (SFA) and the risk of type 2 diabetes mellitus (T2DM). The objective of this study was to investigate the association of dietary SFAs, their food sources, and substitution with other macronutrients, with the risk of T2DM.

The current study was conducted on 2295 adults out of the participants of the Tehran Lipid and Glucose Study (TLGS) based on the inclusion criteria. The baseline intake of SFAs was estimated using a validated 168-item food frequency questionnaire. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of T2DM in tertile categories of SFAs and their different food sources. The risk of T2DM was estimated with multivariable Cox regression for the substitution of SFAs with other macro-nutrients.

Over a median of 8.5 years of follow-up, 10.6% of participants were identified as T2DM patients. The study found no significant associations between the baseline dietary intake of total SFA, lauric acid (LA), myristic acid (MA), palmitic acid (PA), or stearic acid (SA) and the risk of T2DM. However, a higher intake of liquid oils was related to a higher risk of T2DM (HR=1.07, 95% CI=1.00-1.15). Moreover, the substitution of MA for SA was related to an increased risk of T2DM (HR=1.56, 95% CI=1.03-1.93).

There was no significant association between dietary SFAs and the risk of T2DM in the present study. Further prospective studies are needed to clarify the association between dietary fats and T2DM risk.

Various types of fatty acids are simultaneously present in the diet. Therefore, it is important to investigate their combined effects on the occurrence of metabolic diseases. This study aimed to determine the dietary fat quality indices and investigate the relationship between these indices and the risk of metabolic syndrome in an Iranian adult population.

A total of 1713 adults participating in the third phase of the Tehran Lipid and Glucose Study (TLGS), who were free of metabolic syndrome, were selected and followed up to the sixth phase. Dietary intakes were evaluated using a validated food frequency questionnaire. The risk of metabolic syndrome in the sixth phase of TLGS, adjusted for potential confounders, was estimated across the tertiles of all dietary fat quality indices, including atherogenic index, thrombogenic index, health-promoting index, ratio of polyunsaturated fatty acids to saturated fatty acids (PUFA/SFA), ratio of hypo- to hypercholesterolemia, total omega-3 fatty acids, and ratio of linoleic acid to α-linolenic acid (LA/ALA), using Cox proportional hazard regression models.

Over a median of 7.6 years of follow-up (2006-2008 to 2014-2017), 596 cases of metabolic syndrome were identified. After adjustment for confounding variables, there was no significant association between dietary fat quality indices and risk of metabolic syndrome. However, each 1-unit increment in the LA/ALA was associated with a 3% higher risk of metabolic syndrome [hazard ratio (95% confidence interval): 1.03 (1.00-1.01)].

Further prospective studies are needed to clarify the association between dietary fat quality indices and the risk of metabolic syndrome. In the present study, there was no significant association between dietary fat quality indices and metabolic syndrome incidence.

This study aimed to determine the association between the quality and quantity of dietary carbohydrate (CHO) with the risk of pre-diabetes (pre-DM) progression to type 2 diabetes (T2D) and the chance of returning to normal glycemia.

 Dietary CHO quantity (total CHO and dietary fiber) and quality (glycemic index, glycemic load, insulin index, and insulin load) were assessed using a 168-item, semi-quantitative, valid, and reliable food frequency questionnaire in 334 men and women with pre-DM at baseline. The participants were followed for a median of 9 years. Fasting and 2-hours (after oral loading of 75 g glucose) plasma glucose concentrations were measured at baseline and subsequent examinations.

 During the study follow-up, 39.8% of the pre-DM subjects progressed to T2D, and 39.8% returned to normal glycemia. Dietary total CHO, glycemic index, glycemic load, insulin index, and insulin load were not significantly associated with pre-DM regression and progression during the study follow-up. A 25% reduced risk of developing T2D was observed per 5 g/1000 kcal per day by the increased dietary intake of fiber (odds ratio: 0.75, 95% CI: 0.58-0.98; P=0.038).

Total CHO intake and its quality were not associated with the change of glycemic status in pre-DM subjects, while higher intakes of dietary fiber decreased the risk of pre-DM progression to T2D.

Metabolic syndrome refers to a cluster of risk factors for cardiovascular disease and type 2 diabetes, including hypertension, dyslipidemia, increased levels of fasting glucose, and obesity, conditions that often occur together. One common method for inducing metabolic syndrome in rats is diet manipulation, mimicking unhealthy dietary patterns in humans. This review aimed to provide a practical guide for creating a rat model of metabolic syndrome by administrating a high-carbohydrate diet. Metabolic syndrome induction by administrating a high-carbohydrate diet is a simple, common, rapid, practical, and cheap method that does not require advanced equipment. In rat models of metabolic syndrome created by the administration of high-carbohydrate diets, parameters such as the type of carbohydrate used (fructose or sucrose), the dose and duration of sugar administration (5 to 48 weeks), the administration route (drinking water or solid food), and model verification parameters (obesity, dyslipidemia, hypertension, insulin resistance, and hyperglycemia) should be taken into consideration. According to the practical guide developed in this study, administering 20-30% sucrose in the drinking water of rats for 10-15 weeks can reliably create a metabolic syndrome model confirmed by elevated fasting serum levels of triglycerides, insulin, and glucose, as well as insulin resistance. If the administration of 20-30% sucrose in drinking water continues for at least 25 weeks (up to 40 weeks), a rat model of metabolic syndrome will be created presenting with obesity and hypertension. It is noteworthy that the confirmation of model creation requires comparison with both basic conditions and control rats.

Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are essential amino acids that modulate glucose homeostasis, neurotransmission, immune responses, and mitochondrial biogenesis, and thereby, contributing a role in the development of metabolic disorders such as obesity and diabetes. In this review, the relationship between the catabolism of BCAAs and insulin resistance (IR), as well as the effect of exercise training on this pathway, was discussed. Epidemiological studies and review articles published between 1964 and 2023 were collected from PubMed, Google Scholar, and Web of Science databases. Also, to reach Persian language articles, Iranian scientific databases, including the Scientific Information Database (SID), Iran’s Information and Scientific Documents Research Institute (Irandoc), and Iran’s publications database (Magiran), were searched to find relevant papers published between 2001 and 2023. The results of various studies show that plasma BCAAs are either upregulated or downregulated by the first two enzymes in their catabolic pathway, i.e., branched-chain aminotransferase (BCAT) and branched-chain alpha-acid dehydrogenase (BCKD). Therefore, the disruption of the enzymatic complexes that limit the catabolic rate of BCAAs lowers their catabolism and increases the plasma levels of BCAAs, greatly predisposing to the development of diabetes. Exercise training can reduce the accumulation of BCAAs catabolic mediators and reduce or even prevent IR. Improving BCAAs’ catabolism through exercise training and diet control can lead to the recovery or prevention of metabolic diseases such as obesity and diabetes.

Evidence suggests that prolactin and metabolic disorders have a significant impact on the pathophysiology of reproductive disorders in both males and females. This study aimed to summarize the existing literature in this field. In this review, we followed the SANRA checklist to compile relevant studies, and a search was performed until January 2023 using relevant keywords in PubMed, Web of Science, SID, Magiran, and Google Scholar. All articles related to the purpose of the current study were extracted and evaluated by the authors. The available evidence indicates that relatively high prolactin levels within the physiological range appear to be beneficial for metabolism. Dysregulation of this hormone, such as in hyperprolactinemia, can lead to various adverse metabolic effects, including insulin resistance, glucose intolerance, anovulation, defects in gonadotropin secretion, and sexual dysfunction. On the other hand, suppressed levels of prolactin can also disrupt both the reproductive and metabolic systems. The complex interaction between prolactin and metabolic markers in the body is believed to play an important role in metabolic and reproductive health. However, the optimal level of prolactin that reflects metabolic health and fertility in both genders remains unknown. Further research is needed to determine the factors that determine the metabolic role of prolactin in the reproductive system.

Medullary Thyroid Cancer (MTC) is a rare, aggressive, and fatal subtype of thyroid cancer, presenting a significant medical challenge that necessitates prompt and accurate diagnosis and treatment. Recently, attention has shifted towards utilizing circulating tumor markers as a novel liquid biopsy technique, offering the potential for improved precision in diagnosis, outcome prediction, and cancer progression monitoring. Hence, this review aims to analyze the characteristics and biological aspects of Circulating Tumor Cells (CTCs) and Circulating Tumor DNA (ctDNA) in MTC. One of the main objectives is to understand how these markers can enhance diagnosis accuracy, provide better predictive insights, and establish a more substantial basis for treatment strategies tailored to this particular type of cancer. The non-invasive nature of CTCs and ctDNA enables them to reveal molecular and genetic changes in tumors. This information holds promise for enhancing early detection and providing more precise tracking of disease development. Moreover, using these markers could address clinical needs and drive advancements in MTC diagnosis and treatment. These progressions have the potential to significantly improve diagnostic precision and treatment effectiveness, ultimately leading to better outcomes for individuals dealing with this intricate condition.