Inhibitory effects of black phosphorus nanosheets on tumor cell proliferation through downregulation of ADIPOQ and downstream signaling pathways.

Exposure to environmental pollutants, including nanomaterials, has a significant impact on tumor progression. The increased demand for black phosphorus nanosheets (BPNSs), driven by their exceptional properties, raises concerns about potential environmental contamination. Assessing their toxicity on tumor growth is essential. Herein, we employed a range of biological techniques, including cytotoxicity measurement, bioinformatics tools, proteomics, target gene overexpression, Western blot analysis, and apoptosis detection, to investigate the toxicity of BPNSs across A549, HepG-2, MCF-7, and Caco-2 cell lines. Our results demonstrated that BPNSs downregulated the expression of ADIPOQ and its associated downstream pathways, such as AMP-activated protein kinase (AMPK), nuclear factor erythroid 2-related factor 2 (Nrf2), and other unidentified pathways. These downregulated pathways ultimately led to mitochondria-dependent apoptosis. Notably, the specific downstream pathways involved varied depending on the type of tumors. These insightful findings not only confirm the consistent inhibitory effects of BPNSs across different tumor cells, but also elucidate the cytotoxicity mechanisms of BPNSs in different tumors, providing valuable information for their safe application and health risk assessment.

Schnurri-3 controls osteogenic fate of Adipoq-lineage progenitors in bone marrow.

Background: Recently, the osteogenic potential of Adiponectin-labeled adipogenic lineage progenitors (Adipoq-lineage progenitors) in bone marrow has been observed to support bone maintenance and repair. However, little is known about the function of Schnurri-3 (SHN3, also known as HIVEP3) in other mesenchymal lineage cells, apart from its negative regulation of bone formation on osteoblasts. Method: In this study, we used single-cell RNA sequencing (scRNA-seq) profiling to demonstrate that Adipoq-lineage progenitors express higher levels of Shn3 compared to other mesenchymal cell populations in mice and humans. To investigate the role of SHN3 in Adipoq-lineage progenitors, we generated a murine model specifically harboring a Shn3-deficient allele in Adipoq-expressing cells. Information of mice body weight was collected weekly to generate body weight curve. Bone phenotype was analyzed using micro-CT and histomorphometric studies. To eliminate the role of peripheral adipose tissue on bone, we collected adipose wet weight, performed intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and conducted a fat-transplantation study. Osteoblast and osteoclast functions were assessed through toluidine blue staining and TRAP staining, respectively. We further investigated the effect of Shn3 depletion on the differentiation of Adipoq-lineage progenitors through immunostaining and in vitro differentiation assays. Finally, we evaluated whether Shn3 deficiency in Adipoq-lineage progenitors affects the fracture healing process by generating bi-cortical femoral fracture models. Results: Depletion of Shn3 in Adipoq-lineage progenitors resulted in a significant increase in trabecular bone mass and bone formation in vivo, without disrupting whole-body energy metabolism and skeletal development. Consistent with these findings, both cell-lineage tracing and functional assays revealed that Shn3 ablation effectively shifted the cell fate of Adipoq-lineage progenitors towards an osteogenic phenotype in the bone marrow. Furthermore, in vivo studies demonstrated that the lack of Shn3 in Adipoq-lineage progenitors also enhanced bone fracture healing under pathological conditions. Conclusion: Overall, our findings provide a novel strategy for targeting the osteoanabolic potential of bone marrow Adipoq-lineage progenitors as a potential treatment for bone loss-related disorders. Translational potential of this article: We have identified a novel gene target that directs the cell fate of a previously identified non-osteogenic cell population under physiological conditions. This study not only expands the therapeutic value of Shn3 ablation in treating osteoporotic or traumatic bone diseases but also provides new insights into the contribution of bone marrow Adipoq-lineage progenitors to osteogenesis. Thus, this article further supports Shn3 silencing as a valuable approach to treat osteopenia and accelerate fracture healing (see graphical abstract).

Adiponectin Gene Polymorphisms: A Case-Control Study on Their Role in Late-Onset Alzheimer's Disease Risk.

Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5' region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.

Systematic pan-cancer analyses of the potential function of the Golgi scaffold protein PAQR3.

Progesterone and AdipoQ Receptor 3 (PAQR3) is a member of the AdipoQ receptor. Our previous studies have found that PAQR3 plays a role as a candidate inhibitor in cardiac adenocarcinoma, breast cancer, gastric cancer and colorectal cancer, but the systematic analysis of PAQR3 in tumors is currently lacking. The objective of this study was to investigate the prognostic and therapeutic value of PAQR3 in 31 tumors. Through the analysis of TCGA, UALCAN, GEO, GEPIA2, TIMER, Kaplan-Meier plotter, TISIDB and other databases, it was found that the expression level of PAQR3 changed significantly in different tumor types, and the expression level of Neuroblastoma was very high. And the level of Prostate adenocarcinoma is low. In addition, the expression level of PAQR3 in Cholangiocarcinoma, Esophageal carcinoma, Head and neck squamous carcinoma, Liver Hepatocellular Carcinoma, Lung Adenocarcinoma and Lung squamous cell carcinoma was significantly higher than that in normal tissues. However, the expression level of PAQR3 in Breast Cancer, Kidney Renal Clear Cell Carcinoma, Kidney renal papillary cell carcinoma, Prostate Adenocarcinoma, Rectum Adenocarcinoma, Thyroid Cancer and Uterine Corpus Endometrial Carcinoma was lower than that in normal tissues. Subsequently, we explored the value of PAQR3 as a prognostic indicator of cancer. In Acute Myeloid Leukemia, Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Kidney Chromophobe, and Thyroid Cancer, PAQR3 expression was positively correlated with OS and DSS, while in Rectum Adenocarcinoma, PAQR3 expression was negatively correlated with OS. PAQR3 high expression group Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Uveal Melanoma, Kidney Chromophobe and DFI were positively correlated. PAQR3 can be used as a risk factor for the prognosis of multiple tumors. Then, we discussed the correlation between PAQR3 and immunology, and found that PAQR3 has a wide range of mutations in various tumor types, the most common mutation type is missense mutation, and common mutation types also include amplification, depth deletion, splicing, truncation and structural variation. Among the tumor samples with PAQR3 alterations, mutation occurred in all tumor samples except prostate adenocarcinoma and adrenal cortical carcinoma, head and neck squamous cell carcinoma, brain low-grade glioma, and kidney clear cell carcinoma, while esophageal adenocarcinoma had the highest total alteration frequency. PAQR3 was strongly associated with CNV in 18 tumors, particularly in Ovarian cancer, Lung squamous cell carcinoma, and Adenoid cystic carcinoma. On the other hand, PAQR3 has a higher SNV frequency in Uterine Corpus Endometrial Carcinoma, Skin Cutaneous Melanoma and Lung Adenocarcinoma, among which Uterine Corpus Endometrial Carcinoma has the highest SNV frequency. These results showed that PAQR3 expression levels were significantly correlated with tumor mutation load, microsatellite instability, neoantigens, and purity. In summary, PAQR3 can affect the tumor microenvironment and has potential for chemotherapy. Finally, we investigated the role of PAQR3 in tumor resistance and found that the expression of PAQR3 affects the efficacy of multiple chemotherapy drugs. Based on these studies, we found that PAQR3 plays an important role in cancer and has potential in tumor diagnosis and prognosis.

A Systematic Narrative Review on ADIPOQ Gene Variants and its Association with T2DM in the Indian Population.

BACKGROUND: The prevalence of diabetes is rapidly increasing in India, even among young adult individuals. Rare adiponectin gene (ADIPOQ) variants may be predominantly present in Indians and decrease the circulatory levels of APN (Adiponectin). Studies reported that ADIPOQ gene variants were associated with type 2 diabetes mellitus (T2DM) and its complications in the Indian population. OBJECTIVES: To review the association of specific ADIPOQ gene variants with T2DM and its associated complications. MATERIALS & METHODS: A search of Pubmed, Chinhal, Medline, Scopus, Web of Science databases, and Google Scholar search engine was performed to retrieve articles by using the following keywords; "ADIPOQ and T2DM", "ADIPOQ and India," "ADIPOQ gene variants and T2DM", "ADIPOQ gene variants and T2DM and India", "SNPs of ADIPOQ gene and T2DM", "SNPs of ADIPOQ gene and India," SNPs of ADIPOQ gene and T2DM and India". Eligibility criteria for the inclusion of articles: Original, Case-Control Study, and Full-Text articles were published in the English language till the end of April 2023. RESULTS: A total of 540 articles were retrieved. Out of this, only 18 articles were found suitable to include in this systematic narrative review. The most studied ADIPOQ gene variants were found to be +10211T/G (rs17846866), +45T/G (rs2241766), and +276G/T (rs1501299) in different Indian populations. CONCLUSION: It was reviewed that ADIPOQ gene variants +10211T/G (rs17846866), +45T/G (rs2241766), and +276G/T (rs1501299) were predominantly present in the Indian population, and decreasing the circulatory levels of APN and significantly associated with T2DM and its complications.

Progestin and adipoQ receptor 7 (PAQR7) mediate the anti-apoptotic effect of P4 on human granulosa cells and its deficiency reduces ovarian function in female mice.

PURPOSE: PAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood. METHODS: We first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary. RESULTS: The PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7-/- female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7-/- mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively. CONCLUSIONS: The present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.

Histone Lactylation Participates in Psoriasis Progression by Regulating the Adiponectin Expression.

Background: Psoriasis is a chronic inflammatory skin disease characterized by erythema, papules, and plaques. Adiponectin (ADIPOQ) is an important protein hormone secreted by adipose tissue. Here, we aimed to explore the expression of ADIPOQ in psoriasis patients and the moderation effect of histone lactylation on ADIPOQ. Methods: The GSE78097 data set was downloaded from GEO database to analyze the differentially expressed genes (DEGs) in psoriasis. A total of 36 psoriasis patients were recruited to obtain the skin samples. The ADIPOQ protein levels, global lactylation and histone lactylation (H3K18lac) levels were detected by Western blot assay. Chromatin immunoprecipitation (CHIP) assay was performed to detect the combination between H3K18lac and promoter regions of the ADIPOQ. The receiver operating curve (ROC) analysis was used to evaluate the diagnostic value of ADIPOQ in psoriasis. Results: ADIPOQ was decreased in the skin tissues of psoriasis patients. In addition, the global lactylation and H3K18lac levels were significantly decreased in the skin tissues of psoriasis patients. In HaCaT cells, promoting the global lactylation and H3K18lac levels increased the ADIPOQ protein levels, while si-LDHA transfection decreased the ADIPOQ protein levels. The CHIP results indicated that lactylation promoted the binding of promoter regions of the ADIPOQ and H3K18lac. Finally, the ROC analysis showed that ADIPOQ exhibited diagnostic value in psoriasis. Conclusion: This study demonstrated ADIPOQ was decreased in the skin tissues of psoriasis patients, and ADIPOQ has diagnostic value for psoriasis. Furthermore, down-regulation of H3K18lac levels inhibited the transcription of ADIPOQ, which was the key factor of decrease of ADIPOQ levels in psoriasis patients.

Circ_0068087 knockdown attenuates high-glucose-induced human tubular epithelial cell injury in a microribonucleic acid/progestin and adipoQ receptor 3-dependent manner in diabetic nephropathy.

AIMS/INTRODUCTION: Previous studies have shown that circular ribonucleic acid mediates the occurrence of diabetic nephropathy. This study aimed to analyze the effects of circ_0068087 on high-glucose (HG)-induced human kidney 2 (HK2) cell dysfunction. MATERIALS AND METHODS: Circ_0068087, miR-580-3p, and progestin and adipoQ receptor 3 (PAQR3) expression were detected by quantitative reverse transcription polymerase chain reaction. Cell viability and proliferation were investigated by Cell Counting Kit-8 and EdU assays, respectively. The cell apoptotic rate was assessed by flow cytometry. Inflammatory response was assessed by enzyme-linked immunoassays. Oxidative stress was evaluated by a superoxide dismutase activity assay kit and lipid peroxidation malondialdehyde assay kit. Molecular interaction was identified by dual-luciferase reporter assay. RESULTS: Circ_0068087 and PAQR3 expression were significantly upregulated in diabetic nephropathy patients. HG treatment inhibited HK2 cell proliferation, but induced cell apoptosis, inflammation, oxidative stress and epithelial-mesenchymal transition by regulating circ_0068087. Circ_0068087 acted as a microribonucleic acid-580-3p (miR-580-3p) sponge, and miR-580-3p targeted PAQR3. Furthermore, circ_0068087 depletion repressed PAQR3 expression through miR-580-3p. MiR-580-3p inhibitors or PAQR3 introduction attenuated circ_0068087 silencing mediated-effects in HG-treated HK2 cells. CONCLUSION: Circ_0068087 promoted HG-induced HK2 cell injuries by the regulation of the miR-580-3p/PAQR3 pathway.

The Polymorphism rs17300539 in the Adiponectin Promoter Gene Is Related to Metabolic Syndrome, Insulin Resistance, and Adiponectin Levels in Caucasian Patients with Obesity.

Background and Aims: The present study was designed to investigate SNP rs17300539 in the ADIPOQ gene and its relationships with obesity, metabolic syndrome (MS), and serum circulating adiponectin. Methods: The present design involved a Caucasian population of 329 subjects with obesity. Anthropometric and adiposity parameters, blood pressure, biochemical parameters, and the percentage of patients with metabolic syndrome were recorded. The ADIPOQ gene variant (rs17300539) genotype was evaluated. Results: The percentage of patients with different genotypes of the rs17300539 polymorphism in this sample was 86.0% (n = 283) (GG), 11.2% (n = 37) (GA), and 2.7% (n = 9) (AA). The allele frequency was G (0.76) and A (0.24). Applying the dominant genetic model (GG vs. GA + AA), we reported differences between genotype GG and genotype GA + AA for serum adiponectin levels (Delta: 7.5 ± 1.4 ng/mL; p = 0.03), triglycerides (Delta: 41.1 ± 3.4 mg/dL; p = 0.01), fastingcirculating insulin (Delta: 4.9 ± 1.1 mUI/L; p = 0.02), and insulin resistance as HOMA-IR (Delta: 1.4 ± 0.1 units; p = 0.02). The remaining biochemical parameters were not related to the genotype of obese patients. The percentages of individuals with MS (OR = 2.07, 95% CI = 1.3-3.88; p = 0.01), hypertriglyceridaemia (OR = 2.66, 95% CI = 1.43-5.01; p = 0.01), and hyperglycaemia (OR = 3.31, 95% CI = 1.26-8.69; p = 0.02) were higher in GG subjects than patients with A allele. Logistic regression analysis reported an important risk of the presence of metabolic syndrome in GG subjects (OR = 1.99, 95% CI = 1.21-4.11; p = 0.02) after adjusting for adiponectin, dietary energy intakes, gender, weight, and age. Conclusions: The GG genotype of rs17300539 is associated with hypertriglyceridaemia, insulin resistance, low adiponectin levels, and a high risk of metabolic syndrome and its components.

LEP (G2548A-G19A) and ADIPOQ (T45G-G276T) gene polymorphisms are associated with markers for metabolic syndrome.

BACKGROUND AND AIMS: There is a link between genetics with metabolic balance and adiposity homeostasis on metabolic syndrome (MetS). Polymorphism in adipokine genes such as leptin and adiponectin may play an important role in its development. This study aimed to determine the association of the individual and general components of MetS with genetic alterations in LEP (rs7799039 and rs2167270) and ADIPOQ (rs1501299 and rs2241766) genes in the Mexican population. METHODS AND RESULTS: The polymorphisms of the LEP gene rs7799039 and rs2167270, together with rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 328 individuals (n = 131 MetS). The rs7799039 under the recessive inheritance model was found to be associated with increased risk of MetS (OR = 2.16, 95% CI = 1.06-4.37), dyslipidemia (OR = 7.97, 95% CI = 2.17-29.36), low HDL (OR = 7.01, 95% CI = 1.65-29.71) and hypertension (OR = 13.02, 95% CI = 1.76-96.44); the heterozygote demonstrate a protective effect on MetS (OR = 0.48, 95% CI = 0.28-0.88) and diabetes (OR = 0.09, 95% CI = 0.02-0.53) under the over the dominant model. Haplotype analysis showed linkage disequilibrium between the SNPs of ADIPOQ rs1501299/rs2241766, and their association as risk factors for low HDL and hypertension. CONCLUSION: The association of rs7799039 with the presence of MetS, suggests a risk factor for the development of dyslipidemia, as well as its heterozygous as a protective factor for DM. There is a linkage disequilibrium between the SNPs of ADIPOQ.

Potential Association of The Pathogenic Kruppel-like Factor 14 (KLF14) and Adiponectin (ADIPOQ) SNVs with Susceptibility to T2DM.

AIM: To evaluate the associations of the pathogenic variants in Kruppel-like Factor 14 (KLF 14) and Adiponectin (ADIPOQ) with susceptibility to type 2 diabetes mellitus (T2DM). BACKGROUND: Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease characterized by increased blood sugar and caused by resistance to insulin in peripheral tissues and damage to pancreatic beta cells. Kruppel-like Factor 14 (KLF-14) is proposed to be a regulator of metabolic diseases, such as diabetes mellitus (DM) and obesity. Adiponectin (ADIPOQ) is an adipocytokine produced by the adipocytes and other tissues and was reported to be involved in T2DM. OBJECTIVES: To study the possible association of the KLF-14 rs972283 and ADIPOQ-rs266729 with the risk of T2DM in the Saudi population. METHODS: We have evaluated the association of KLF-14 rs972283 C>T and ADIPOQ-rs266729 C>G SNV with the risk to T2D in the Saudi population using the Amplification Refractory Mutation System PCR (ARMS-PCR), and blood biochemistry analysis. For the KLF-14 rs972283 C>T SNV we included 115 cases and 116 healthy controls, and ADIPOQ-rs266729 C>G SNV, 103 cases and 104 healthy controls were included. RESULTS: Results indicated that the KLF-14 rs972283 GA genotype and A allele were associated with T2D risk with OR=2.14, p-value= 0.014 and OR=1.99, p-value=0.0003, respectively. Results also ADIPOQ-rs266729 CG genotype and C allele were associated with an elevated T2D risk with an OR=2.53, p=0.003 and OR=1.66, p-value =0.012, respectively. CONCLUSION: We conclude that SNVs in KLF-14 and ADIPOQ are potential loci for T2D risk. Future large-scale studies to verify these findings are recommended. These results need further verifications in protein functional and large-scale case control studies before being introduced for genetic testing.

Rare Variants of Obesity-Associated Genes in Young Adults with Abdominal Obesity.

The increase in the prevalence of overweight, obesity and associated diseases is a serious problem. The aim of the study was to identify rare variants in obesity-associated genes in young adults with abdominal obesity in our population and to analyze information about these variants in other populations. Targeted high-throughput sequencing of obesity-associated genes was performed (203 young adults with an abdominal obesity phenotype). In our study, all of the 203 young adults with abdominal obesity had some rare variant in the genes associated with obesity. The widest range of rare and common variants was presented in ADIPOQ, FTO, GLP1R, GHRL, and INS genes. The use of targeted sequencing and clinical criteria makes it possible to identify carriers of rare clinically significant variants in a wide range of obesity-associated genes and to investigate their influence on phenotypic manifestations of abdominal obesity.

Identification of autophagy and angiogenesis modulators in colorectal cancer based on bioinformatics analysis.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-related death worldwide. The purpose of this study was to discover novel molecular pathways and potential prognosis biomarkers. To achieve this, we acquired five microarray datasets from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes between CRC and adjacent normal tissue samples and further validated them using The Cancer Genome Atlas (TCGA) database. Using various analytical approaches, including the construction of a competing endogenous RNA (ceRNA) network, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses, as well as survival analysis, we identified key genes and pathways associated with the diagnosis and prognosis of CRC. We obtained a total of 185 differentially expressed genes, comprising 17 lncRNAs, 30 miRNAs, and 138 mRNAs. The ceRNA network consisted of 17 lncRNAs, 25 miRNAs, and 7 mRNAs. Among the 7 mRNAs involved in the ceRNA network, SLC7A5 and KRT80 were found to be upregulated, while ADIPOQ, CCBE1, KCNB1, CADM2, and CHRDL1 were downregulated in CRC. Further analysis revealed that ADIPOQ and SLC7A5 are involved in the AMPK and mTOR signaling pathway, respectively. In addition, survival analysis demonstrated a statistically significant relationship between ADIPOQ, SLC7A5, and overall survival rates in CRC patients. In conclusion, our findings suggest that downregulation of ADIPOQ and upregulation of SLC7A5 in tumor cells lead to increased mTORC1 activity, reduced autophagy, enhanced angiogenesis, and ultimately contribute to cancer progression and decreased survival in CRC patients.

Translational control of murine adiponectin expression by an upstream open reading frame element.

Adiponectin, an adipocyte-specific secretory protein encoded by the ADIPOQ gene has a causal role in insulin resistance. Anti-diabetic drugs increase plasma adiponectin by a poorly understood, post-transcriptional mechanism enhancing insulin sensitivity. Deletion analysis of a reporter bearing the mouse Adipoq mRNA 5'-leader identified an inhibitory cis-regulatory sequence. The 5'-leader harbours two potential upstream open reading frames (uORFs) overlapping the principal downstream ORF. Mutation of the uORF ATGs increased reporter translation ~3-fold, indicative of a functional uORF. uORFs are common in mammalian mRNAs; however, only a select group resist translational repression by the integrated stress response (ISR). Thapsigargin (TG), which induces endoplasmic reticulum (ER) stress and the ISR, enhanced expression of a reporter bearing the Adipoq 5'-leader; polysome profiling verified translation-stimulation. TG-stimulated translation was absent in cells defective in Ser51 phosphorylation of eukaryotic initiation factor 2α (eIF2α), required for the ISR. To determine its role in expression and function of endogenous adiponectin, the upstream uORF was disrupted by CRISPR-Cas9-mediated mutagenesis of differentiated mouse 3T3-L1 adipocytes. uORF disruption in adipocytes increased adiponectin expression, triacylglycerol accumulation, and glucose uptake, and inhibited paracrine muscle and liver cell expression of gluconeogenic enzymes, establishing an important role of the uORF in adiponectin-mediated responses to stress.

GCKR and ADIPOQ gene polymorphisms in women with gestational diabetes mellitus.

AIMS: To investigate the associations of GCKR and ADIPOQ variants with the risk of gestational diabetes mellitus (GDM) in Chinese women. METHODS: GCKR rs1260326, ADIPOQ rs266729, and rs1501299 were selected and genotyped in 519 GDM patients and 498 controls. Candidate SNPs were genotyped using multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods, and the association of these SNPs with GDM was analyzed. RESULTS: We found that GCKR rs1260326 was significantly associated with an increased risk of GDM in the allele model, the codominant model (CC vs. TT), the dominant model, the recessive model, and the genotypic model distributions (p = 0.0029, p = 0.0022, p = 0.0402, p = 0.0038, and p = 0.0028, respectively). The rs1260326 polymorphism was shown to be associated with 1 h-OGTT level and gravidity in GDM patients (CC vs. TT: p = 0.0475 and p = 0.0220, respectively). Diastolic blood pressure (DBP) was significantly higher in the GDM patients with the rs266729 GG genotype compared to those with the CC or CG genotype (p = 0.0444 and p = 0.0339, respectively). The DBP of the GDM patients with the rs1501299 GT genotype was lower than that of those with the GG genotype (p = 0.0197). There was a weak linkage disequilibrium value between the GCKR and ADIPOQ SNPs. CONCLUSIONS: The genes GCKR and ADIPOQ may be involved in the pathophysiology of GDM.

Study Protocol for the Interactions between Dietary Patterns and ARL15 and ADIPOQ Genes Polymorphisms on Cardiometabolic Risk Factors.

Background: Cardiovascular diseases (CVDs) are recognized as one of the leading causes of death worldwide. Studies have shown the impact of genetic predisposition and dietary factors on developing these diseases. Dietary patterns and genetic factors such as polymorphisms related to the level of adiponectin may also interact with each other and produce variances in the effects of these factors on different individuals. The purpose of this study is to investigate the interactions between food intake patterns and polymorphisms on ADIPOQ and ARL15 genes in relation to cardiometabolic risk factors. Methods: This cross-sectional study is conducted on 380 adults (20 to 70 years old) living in Yazd, Iran. Individuals were selected from the participants in Yazd Health Study (YaHS) and its sub-study called Taghziyeh Mardom-e Yazd (TAMYZ) after reviewing the inclusion and exclusion criteria. YaHS is a population-based cohort study which has been conducted on 9962 adults living in Yazd since 2014. In the present study, rotated principle component analysis (PCA) with Varimax rotation is used to identify the major dietary patterns. The polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method is used in order to identify rs1501299 and rs6450176 variants (on ADIPOQ and ARL15 genes, respectively). General linear models (GLM) as well as regression models are used to investigate the interactions between the studied genotypes and the extracted dietary patterns. Conclusions: The results of this study can help to personalize dietary recommendations for the prevention of CVDs according to the genetic predisposition of individuals.

Dissecting the Molecular Role of ADIPOQ SNPs in Saudi Women Diagnosed with Gestational Diabetes Mellitus.

The traditional definition of gestational diabetes mellitus (GDM) is the leading cause of carbohydrate intolerance in hyperglycemia of varying severity, with onset or initial detection during pregnancy. Previous studies have reported a relationship among obesity, adiponectin (ADIPOQ), and diabetes in Saudi Arabia. ADIPOQ is an adipokine that is produced and secreted by adipose tissue involved in the regulation of carbohydrate and fatty acid metabolism. This study investigated the molecular association between rs1501299, rs17846866, and rs2241766 single-nucleotide polymorphisms (SNPs) in ADIPOQ and GDM in Saudi Arabia. Patients with GDM and control patients were selected, and serum and molecular analyses were performed. Statistical analyses were performed on clinical data, Hardy Weinberg Equilibrium, genotype and allele frequencies, multiple logistic regression, ANOVA, haplotype, linkage disequilibrium, as well as MDR and GMDR analyses. The clinical data showed significant differences in various parameters between the GDM and non-GDM groups (p < 0.05). In GDM women with alleles, genotypes, and different genetic models, the rs1501299 and rs2241766 SNPs showed a strong association (p < 0.05). Multiple logistic regression analysis revealed a negative correlation (p > 0.05). This study concluded that rs1501299 and rs2241766 SNPs were strongly associated with GDM in women in Saudi Arabia.

Effects of ADIPOQ and NOS3 SNPs/haplotypes on blood pressure control in patients with adherence to antihypertensive therapy.

Aim: We examined whether ADIPOQ (rs266729 and rs1501299) and NOS3 (rs3918226 and rs1799983) SNPs or the haplotypes formed by them, affect blood pressure (BP) control in 196 patients with adherence to antihypertensive therapy grouped into controlled (BP <140/90 mmHg) and uncontrolled (BP ≥140/90 mmHg) hypertension. Materials & methods: The average of the three most recent BP measurements was retrieved from the patients' electronic medical records. Adherence to antihypertensive therapy was evaluated using the Morisky-Green test. Haplotype frequencies were estimated using Haplo.stats. Multiple logistic/linear regression analyses were adjusted for the covariates ethnicity, dyslipidemia, obesity, cardiovascular disease and uric acid. Results: ADIPOQ rs266729 genotypes CG (additive model) and CG+GG (dominant model) were associated with uncontrolled hypertension and CG was associated with higher systolic BP and mean arterial pressure (p < 0.05). ADIPOQ haplotypes 'GT' and 'GG' were associated with uncontrolled hypertension and 'GT' was associated with higher diastolic BP and mean arterial pressure (p < 0.05). Conclusion: ADIPOQ SNPs and haplotypes affect BP control in hypertensive patients undergoing treatment.

Resveratrol inhibits the formation and accumulation of lipid droplets through AdipoQ signal pathway and lipid metabolism lncRNAs.

Resveratrol (RES) is one of the best-known bioactive polyphenols that has received much attention in recent years because of its importance to anti-obesity. However, the exact mechanism underlying this effect and whether it can improve lipid metabolism by regulating the long-chain noncoding RNA (lncRNA) remains unclear. In this study, 24 healthy crossbred castrated boars were fed a basal diet (control) and a basal diet supplemented with 200 mg, 400 mg or 600 mg RES per Kilogram (kg) of feed for 41 d, respectively. We found that 400 mg/kg and 600 mg/kg RES-supplemented diet did not affect growth rate, but reduced significantly subcutaneous adipose thickness, carcass fat rate, greater dramatically the serum concentration of adiponectin and high-density lipoprotein in pigs. Further, we verified that RES could inhibit the formation and accumulation of lipid droplets by AdipoQ-AdipoR1-AMPKα and AdipoQ-AdipoR2-PPARα signal pathway in vivo and vitro (3T3-L1 preadipocytes). Transcriptome analyses found that 5 differently expressed (DE) lncRNAs and 77 mRNAs in subcutaneous adipose between control group and 400 mg/kg RES group, which mainly involved in "adipocytokine signaling pathway," "Wnt signaling pathway," "PI3K-Akt signaling pathway" and "MAPK signaling pathway." In conclusion, RES can inhibit the formation and accumulation of lipid droplets through AdipoQ signal pathway and lipid metabolism-related lncRNAs. Our results provide a new insight on the molecular mechanism of RES as a nutritional agents to the prevention and treatment for obesity.

Profiling of N6-methyladenosine methylation in porcine longissimus dorsi muscle and unravelling the hub gene ADIPOQ promotes adipogenesis in an m6A-YTHDF1-dependent manner.

BACKGROUND: Intramuscular fat (IMF) content is a critical indicator of pork quality, and abnormal IMF is also relevant to human disease as well as aging. Although N6-methyladenosine (m6A) RNA modification was recently found to regulate adipogenesis in porcine intramuscular fat, however, the underlying molecular mechanisms was still unclear. RESULTS: In this work, we collected 20 longissimus dorsi muscle samples with high (average 3.95%) or low IMF content (average 1.22%) from a unique heterogenous swine population for m6A sequencing (m6A-seq). We discovered 70 genes show both differential RNA expression and m6A modification from high and low IMF group, including ADIPOQ and SFRP1, two hub genes inferred through gene co-expression analysis. Particularly, we observed ADIPOQ, which contains three m6A modification sites within 3' untranslated and protein coding region, could promote porcine intramuscular preadipocyte differentiation in an m6A-dependent manner. Furthermore, we found the YT521­B homology domain family protein 1 (YTHDF1) could target and promote ADIPOQ mRNA translation. CONCLUSIONS: Our study provided a comprehensive profiling of m6A methylation in porcine longissimus dorsi muscle and characterized the involvement of m6A epigenetic modification in the regulation of ADIPOQ mRNA on IMF deposition through an m6A-YTHDF1-dependent manner.