The role of CD36-Fabp4-PPARγ in skeletal muscle involves insulin resistance in intrauterine growth retardation mice with catch-up growth.

BACKGROUND: Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society. METHODS: The pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes. RESULTS: After dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05). CONCLUSIONS: LBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways.

Clinical and genetic characteristics of a child with Sotos syndrome and attention-deficit/hyperactivity disorder: A case report.

BACKGROUND: Sotos syndrome is an autosomal dominant disorder, whereas attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition. This report aimed to summarize the clinical and genetic features of a pediatric case of Soros syndrome and ADHD in a child exhibiting precocious puberty. CASE SUMMARY: The patient presented with accelerated growth and advanced skeletal maturation; however, she lacked any distinct facial characteristics related to specific genetic disorders. Genetic analyses revealed a paternally inherited heterozygous synonymous mutation [c.4605C>T (p.Arg1535Arg)]. Functional analyses suggested that this mutation may disrupt splicing, and bioinformatics analyses predicted that this mutation was likely pathogenic. After an initial diagnosis of Sotos syndrome, the patient was diagnosed with ADHD during the follow-up period at the age of 8 years and 7 months. CONCLUSION: The potential for comorbid ADHD in Sotos syndrome patients should be considered to avoid the risk of a missed diagnosis.

Gestational Weight Gain and Small for Gestational Age in Obese Women: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis evaluates the relationship between gestational weight gain and the risk of small for gestational age in obese pregnant women. Methods: Studies were identified by searching the Web of Science, Embase, and PubMed databases up to June 30th, 2022. The meta-analysis was carried out to determine the risk of small for gestational age with gestational weight gain (GWG) below the 2009 Institute of Medicine (IOM) guidelines compared with within the guidelines in obese women. The Newcastle-Ottawa Scale was used to assess the methodological quality. The chi-squared test, Q test, and I2 test were used to evaluate statistical heterogeneity. Subgroup analyses were conducted, and publication bias was assessed by funnel plots and Egger's test. Sensitivity analyses were performed for three groups of obese people (I: BMI 30-34.9 kg/m2, II: BMI 35-39.9 kg/m2, and III: BMI ≥ 40 kg/m2) to examine the association of obesity and SGA. Results: A total of 788 references were screened, and 29 studies (n = 1242420 obese women) were included in the systematic review. Obese women who gained weight below the IOM guideline had a higher risk of SGA than those who gained weight within the guideline (OR = 1.27, 95% CI = 1.16-1.38, Z = 5.36). Both weight loss (<0 kg) and inadequate weight (0-4.9 kg) during pregnancy in obese women are associated with an increased risk of SGA (OR = 1.50, 95% CI = 1.37-1.64, Z = 8.82) (OR = 1.18, 95% CI = 1.14-1.23, Z = 8.06). The same conclusions were also confirmed for the three obesity classes (I: OR = 1.38, 95% CI = 1.29-1.47; II: OR = 1.39, 95% CI = 1.30-1.49; and III: OR = 1.26, 95% CI = 1.16-1.37). Subgroup analysis by country showed that GWG below guidelines in obese women of the USA and Europe was associated with risk for SGA (USA (OR = 1.30, 95% CI = 1.15-1.46), Europe (OR = 1.24, 95% CI = 1.11-1.40)) and not in Asia (OR = 1.17, 95% CI = 0.91-1.50). Conclusion: Our findings indicated that obese pregnant women who had weight loss or inadequate weight (0-4.9 kg) according to the IOM guideline had increased risks for SGA. Moreover, we also evaluated that gestational weight loss (<0 kg) in these pregnancies was associated with an increased risk for SGA compared with inadequate weight (0-4.9 kg) in these pregnancies. Therefore, the clinical focus should assist obese women to achieve GWG within the IOM guidelines to decrease the risk for SGA.

Promotion of IL­17/NF­κB signaling in autoimmune thyroid diseases.

IL-17 and other cytokines have a number of immunomodulatory effects on thyroid cells. The present study investigated the changes and correlations amongst IL-17, NF-κB, IL-6, IL-10, interferon-γ (IFN-γ), TNF-α, IL-2 and IL-4 in patients with different autoimmune thyroid diseases in order to further clarify the pathogenesis of autoimmune thyroid disease. A total of 82 patients with autoimmune thyroid diseases (41 with Graves' disease and 41 with Hashimoto's thyroiditis) and 53 healthy controls were enrolled. All relevant thyroid hormones were detected by electrochemiluminescence analyzer. The serum levels of IL-17 and other cytokines were detected using flow cytometry, NF-κB was detected by ELISA, reverse transcription-quantitative PCR was used to detect the protein expression of various mRNAs, and the correlations between IL-17 and these factors were analyzed. Significant differences occurred amongst all groups. NF-κB, TNF-α, IL-6, IL-17 and their mRNA levels were significantly higher in the healthy controls compared with those in the patients; whereas IFN-γ and IL-10 levels were significantly lower in the healthy controls compared with those in the patients . Correlation analysis showed that the expression levels of IL-17 and its mRNA were significantly positively correlated with the expression levels of NF-κB, IL-6, thyroid peroxidase antibody, thyroid gland globulin, thyroglobulin antibody, TNF-α and IFN-γ, and were also significantly negatively correlated with IL-10 . These findings suggested that IL-17 was elevated in patients with autoimmune thyroid disease and that IL-17 could activate the NF-κB signaling pathway, stimulate the production and release of inflammatory factors such as TNF-α, IL-6 and IFN-γ and participate in the pathogenesis of autoimmune thyroid injury.

Effect of glucagon-like peptide-1 receptor agonists on fat distribution in patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS/INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1Ras) are widely used to treat type 2 diabetes. They not only reduce glucose, but also have a positive effect on weight loss. However, few studies have reported the effect of GLP-1Ras on fat distribution. MATERIALS AND METHODS: PubMed, Cochrane, Embase and ClinicalTrials.gov were searched for randomized controlled trials on GLP-1Ras and type 2 diabetes, published from inception to June 2021. Our main outcomes were the reductions of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Other anthropometric outcomes were also assessed. We used the Cochrane Collaboration tools to assess the risk of bias in the included studies. The quality of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation profiler version 3.6. Review Manager 5.4.1 and Stata 16.0 were used for data analysis. RESULTS: A total of 10 studies involving 541 patients were included. Compared with the control groups, the GLP-1Ras groups showed reductions in VAT (standard mean difference -0.54, 95% confidence interval [CI] -0.92, -0.17, I2 = 79%, P = 0.005) and SAT (standard mean difference -0.44, 95% CI -0.60, -0.27, I2 = 44%, P < 0.00001). In addition, bodyweight (weighted mean difference -3.59, 95% CI -4.30, -2.88, I2 = 0%, P < 0.00001), waist circumference (weighted mean difference -3.09, 95% CI -4.66, -1.52, I2 = 70%, P = 0.0001) and body mass index (weighted mean difference -1.11, 95% CI -1.35, -0.86, I2 = 47%, P < 0.00001) were significantly decreased. According to the Grades of Recommendation, Assessment, Development and Evaluation approach, the level of evidence was low or moderate. CONCLUSION: This study highlights that GLP-1Ras, especially liraglutide and exenatide, might play an active role in fat distribution in patients with type 2 diabetes. After treatment with GLP-1Ras, both VAT and SAT decreased, and the decrease of VAT was numerically greater than that of SAT.

Changes of ACE2 in different glucose metabolites and its relationship with COVID-19.

BACKGROUND: To study the changes and effects of angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang1-7) and ACE/AngII in people with different glucose metabolisms and to explore the possible mechanisms underlying the severity of COVID-19 infection in diabetic patients. METHODS: A total of 88 patients with type 2 diabetes, 72 patients with prediabetes (impaired fasting glucose, 30 patients; impaired glucose regulation, 42 patients), and 50 controls were selected. Changes and correlations of ACE2, Ang1-7 and other indicators were detected among the three groups. Patients were divided into four groups according to the course of diabetes: <1 year, 1-5 years, 5-10 years, and >10 years. ACE2 and Ang1-7 levels were compared and analyzed. RESULTS: ACE2 and Ang1-7 increased with the severity of diabetes (P0 < .05 or P < .01). The levels of ACE2 and Ang1-7 in the longer course group were lower than those in the shorter course group, whereas the levels of ACE, Ang II, and interleukin-6 (IL-6) gradually increased (P < .05). Pearson correlation analysis showed that ACE2 was positively correlated with IL-6, FBG, and 2hPBG levels in the prediabetes group. In the diabetic group, ACE2 was positively correlated with Ang1-7 and negatively correlated with ACE, AngII, IL-6, and C-reactive protein levels. Multiple linear regression analysis showed that IL-6 and ACE were the main factors influencing ACE2 in the diabetic group. CONCLUSION SUBSECTIONS: ACE2/Ang1-7 and ACE/AngII systems are activated, and inflammatory cytokine release increases in prediabetes. With the prolongation of the disease course, the effect of ACE2/Ang1-7 decreased gradually, while the effect of ACE/AngII increased significantly. Dysfunctions of ACE2/Ang1-7 may be one of the important mechanisms underlying the severity of COVID-19 infection in patients with diabetes.

Effect of visfatin on the function of endothelial progenitor cells in high-fat-fed obese rats and investigation of its mechanism of action.

The aim of this study was to study the quantity change of endothelial progenitor cells (EPCs) in obese rats fed a high-fat-diet and to investigate the correlation of EPC numbers with visfatin. The impact of visfatin on the quantity and function of EPCs were further investigated by cell culture methods. Male Wistar rats were fed on either a standard diet (NC group) or a high-fat diet (HF group) for 16 weeks. Serum visfatin, Lee's index and the protein expression of visfatin in viseral adipose tissue (VAT) were determined. Bone marrow EPCs in 2 groups of rats were isolated, cultured and counted. EPCs primarily cultured from control male Wistar rats were treated with different concentrations of visfatin. The quantity, migration and adhesion capacity of EPCs were evaluated after visfatin treatment. Protein expression of nuclear factor-κB (NF-κB) in the nuclei of EPCs was detected. After 16-week feeding, body weight, serum visfatin, Lee's index and visfatin contents in viseral fat were significantly increased in the HF group compared with NC group (P<0.01 or P<0.05). The quantity of EPCs primarily cultured from rats in HF group was lower than that in NC group. The quantity of EPCs was negatively correlated with serum visfatin levels, visceral fat, fasting blood glucose, HOMA-IR, total cholesterol, triglyceride and body weight (P<0.01). In cultured EPCs, visfatin significantly increased the protein expression of NF-κB in EPC nuclei (P<0.01) in a dose-dependent manner. The migration and adhesion capacity were impaired by visfatin treatment (P<0.01). In conclusion, bone marrow-derived EPCs decrease in number and have impaired migration and adhesion function in high-fat-fed obese rats, along with increased serum visfatin and protein contents in VAT. Visfatin may have an impact on the quantity and function of EPCs through the NF-κB pathway.