Peroxisome Proliferator-activated Receptor Gamma Gene Research Articles

The Identification of Methylation Profiles of FTO and PPARG Genes in Type 2 Diabetes Mellitus Patients

Type 2 diabetes (T2DM) is a complex, metabolic disease driven by genetic susceptibilities, environmental interactions, and various genes. Nowadays, increasing number of studies show the relationship between diabetes mellitus (DM) and epigenetics, especially DNA methylation. In this study, we aimed to measure the methylation levels of fat mass and obesity associated (FTO) and peroxisome proliferator activated receptor gamma (PPARG) in the peripheral blood samples of patients with clinical diagnosis of T2DM. In our study, whole blood was taken from T2DM patients (n=43) who applied to the Endocrinology Outpatient Clinic and from age-gender-matched healthy individuals (n=42). After the bisulfide conversion of isolated genomic DNAs from whole blood samples, the methylation profiles of target genes were analyzed with methyl-specific PCR and gel electrophoresis methods. Post-statistical analyses, no significant difference was found between the T2DM and control groups regarding FTO methylation status. The methylation level of PPARG gene in T2DM was significantly higher compared to the control group. Given the insulin sensitizing effects of PPARG, our findings confirm the possibility that methylation-mediated suppression of PPARG gene expression may lead to elevation of insulin resistance in T2DM patients. Further gene expression studies with more patients and quantitative methods will be required to better understand the effects of methylation in the PPARG gene in T2DM patients and its relationship to the disease.

MicroRNA-34a and promoter methylation contribute to peroxisome proliferator-activated receptor gamma gene expression in patients with type 2 diabetes

AimsThis study aimed to investigate the roles of DNA methylation and miR-34a in the regulation of peroxisome proliferator-activated receptor gamma (PPARγ) in patients with type 2 diabetes (T2D). MethodsWe investigated the methylation status of four regions of the PPARγ promoter and PPARγ expression in a panel of 84 T2D patients using methylation-specific PCR (MSP) and RT-qPCR, respectively. Moreover, we quantified DNA methyltransferases (DNMTs) expression and global DNA methylation levels by RT-qPCR and ELISA, respectively. We measured the expression levels of miR-34a and protein expression of PPARγ by stem-loop RT-qPCR and ELISA, respectively. ResultsWe found significant DNA hypermethylation in the R2 and R3 regions of the PPARγ promoter in people with diabetes. Functionally, this was associated with a significant reduction in PPARγ expression. In addition, we observed a significant increase in 5-methylcytosine levels in people with diabetes. A marked increase in circulating miR-34a in the early stages of T2D (up to 10 years) and a significant decrease in circulating miR-34a with increasing diabetes duration from 10 years after the onset of diabetes. Interestingly, upregulation of DNA methyltransferases 1 (DNMT1), DNMT3A, and DNMT3B was observed in people with diabetes, and the average expression of DNMTs was negatively correlated with circulating miR-34a levels. In contrast, the serum protein level of PPARγ, a direct target of miR-34a, increased considerably with diabetes duration and showed a negative correlation with circulating miR-34a, cholesterol, triglyceride, and low-density lipoprotein. ConclusionPPARγ promoter hypermethylation and miR-34a upregulation are associated with T2D pathogenesis through PPARγ dysregulation.

Effects of Resistance Training, Estrogen Therapy, and Calcium Chitosan Supplement Containing Vitamin D on Bone Turnover in Ovariectomized Rats: An Experimental-Comparative Study

Background: Hormone therapy is a highly effective method for treating menopausal disorders. However, its side effects may include an increased risk of cancer, heart disease, and pulmonary embolism. Previous research has demonstrated that both exercise and nutrition separately have positive effects on menopausal symptoms. Therefore, we suggest that combining exercise and nutrition interventions may provide a synergistic effect, yielding results at least similar to those of estrogen (Est) therapy. Objectives: This study aims to compare the independent and combined effects of resistance training (RT), Est therapy, and vitamin D calcium chitosan (Vit D + Ca++ + Chit) supplementation on markers of bone turnover in ovariectomized (OVX) rats. Methods: Forty-two female Wistar rats were randomly divided into seven groups (n = 6 per group): (1) healthy-control (He-Co), (2) OVX-Vit D + Ca++ + Chit + RT, (3) OVX-saline (Sal) + Est + RT, (4) Sal + RT, (5) OVX-Vit D + Ca++ +Chit, (6) OVX-Sal + Est, and (7) OVX-Control (OVX-Co). Bone samples were extracted 48 hours after the final session. Two-way ANOVAs were used to determine differences in intervention effects between groups. The alpha level was set to 0.05. Results: Ovariectomy (OVX) decreased bone tissue expression of alkaline phosphatase (ALP) and osterix (OSX) while increasing peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression. Ovariectomy also decreased the number of osteocytes and osteoblasts while increasing the number of osteoclasts. Resistance training (RT) and Vit D + Ca++ + Chit intake increased bone tissue expression of ALP, OSX, and PPAR-γ gene expression. Additionally, RT and Vit D + Ca++ + Chit supplementation increased the number of osteocytes and osteoblasts and decreased the number of osteoclasts. Conclusions: The combined interventions had synergistic effects compared to each intervention separately on ALP, osteocyte, osteoblast, and osteoclast observations. Therefore, combining RT with Vit D + Ca++ + Chit could be a non-pharmacological approach to address bone turnover alterations caused by OVX.

The Analysis of ECE1 and PPARG Variants in the Development of Osteopenia and Osteoporosis in Postmenopausal Women.

Osteoporosis is a multifactorial systemic skeletal disease that is characterized by a low bone mineral density (BMD) and the microarchitectural deterioration of bone tissue, leading to bone fragility. The search for new genes that may play an important role in the regulation of bone mass and the development of osteoporosis is ongoing. Recently, it was found that altering the activity of the endothelin-1-converting enzyme encoded by the ECE1 gene may affect bone mineral density (BMD). Another gene involved in the process of osteoblast differentiation and maturation is believed to be PPARG (peroxisome proliferator-activated receptor gamma). This participates in regulating the transformation of stem cells and affects the process of bone formation and resorption. Therefore, we analyzed the association of the ECE1 and PPARG variants with osteopenia and osteoporosis risk in the Polish population. This study included a group (n = 608) of unrelated Polish women (245 individuals with osteoporosis (aged: 57 ± 9), 109 individuals with osteopenia (aged: 53 ± 8) and 254 healthy controls (aged: 54 ± 8)). The real-time PCR technique was used to determine the genetic variants for rs213045 (-338G>T) and rs213046 (-839A>C) of the ECE1 gene and rs1801282 (Pro12Ala, C>G) of the PPARG gene. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, in the densitometric results, lower median Z-score values were observed for the T allele compared to the G allele for the rs213045 variant of the ECE1 gene (-1.11 ± 1.07 vs. -0.78 ± 1.21, p = 0.021). Moreover, the TT genotype for the rs213045 variant was more common in women with osteopenia (13.8%, OR = 2.82, p < 0.05) and osteoporosis (7.8%, OR = 1.38, p > 0.05) compared to the control group (5.5%). Additionally, our results suggested that the T allele of rs213045 was more common in women with osteopenia compared to the controls. We further observed that the haplotype containing two major GA alleles of ECE1 (rs213045, rs213046) could reduce the risk of osteopenia in our population. Finally, we found that women with osteoporosis had statistically significantly lower body mass and BMI values compared to the control group. Our results suggest that the ECE1 rs213045 variant may increase the risk of osteopenia. However, the data obtained require confirmation in further studies.

Identification and experimental validation of immune-related gene PPARG is involved in ulcerative colitis

BackgroundThe pathophysiology of ulcerative colitis (UC) is believed to be heavily influenced by immunology, which presents challenges for both diagnosis and treatment. The main aims of this study are to deepen our understanding of the immunological characteristics associated with the disease and to identify valuable biomarkers for diagnosis and treatment. MethodsThe UC datasets were sourced from the GEO database and were analyzed using unsupervised clustering to identify different subtypes of UC. Twelve machine learning algorithms and Deep learning model DNN were developed to identify potential UC biomarkers, with the LIME and SHAP methods used to explain the models' findings. PPI network is used to verify the identified key biomarkers, and then a network connecting super enhancers, transcription factors and genes is constructed. Single-cell sequencing technology was utilized to investigate the role of Peroxisome Proliferator Activated Receptor Gamma (PPARG) in UC and its correlation with macrophage infiltration. Furthermore, alterations in PPARG expression were validated through Western blot (WB) and immunohistochemistry (IHC) in both in vitro and in vivo experiments. ResultBy utilizing bioinformatics techniques, we were able to pinpoint PPARG as a key biomarker for UC. The expression of PPARG was significantly reduced in cell models, UC animal models, and colitis models induced by dextran sodium sulfate (DSS). Interestingly, overexpression of PPARG was able to restore intestinal barrier function in H2O2-induced IEC-6 cells. Additionally, immune-related differentially expressed genes (DEGs) allowed for efficient classification of UC samples into neutrophil and mitochondrial metabolic subtypes. A diagnostic model incorporating the three disease-specific genes PPARG, PLA2G2A, and IDO1 demonstrated high accuracy in distinguishing between the UC group and the control group. Furthermore, single-cell analysis revealed that decreased PPARG expression in colon tissue may contribute to the polarization of M1 macrophages through activation of inflammatory pathways. ConclusionIn conclusion, PPARG, a gene related to immunity, has been established as a reliable potential biomarker for the diagnosis and treatment of UC. The immune response it controls plays a key role in the progression and development of UC by enabling interaction between characteristic biomarkers and immune infiltrating cells.

Combined effect of pantoprazole and mesenchymal stem cells on experimentally induced gastric ulcer: implication of oxidative stress, inflammation and apoptosis pathways

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.

Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway.

Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

The RAAS system SNPs polymorphism is associated with essential hypertension risk in rural areas in northern China.

Objectives: Epidemiological evidence has shown that genetics and environment are associated with the risk of hypertension. However, the specific SNP effects of a cluster of crucial genes in the RAAS system on the risk of hypertension are unclear. Methods: A case-control study was performed on the baseline participants of Environment and Chronic Disease in Rural Areas of Heilongjiang China (ECDRAHC) study. According to the inclusion and exclusion criteria, 757 subjects (428 hypertensive patients) were enrolled. A total of 32 SNP sites and related haplotypes, involved in AGT (angiotensinogen), ACE (angiotensin-converting enzyme), AGTR1, CYP11B2 (aldosterone-synthase), LDLR (low-density lipoprotein receptor), LRP5 (low-density lipoprotein receptor associated protein 5), LRP6 (low-density lipoprotein receptor associated protein 6), PPARG (peroxisome proliferator-activated receptor gamma) and ACE2 (angiotensin-converting enzyme 2) genes which exert important roles in renin-angiotensin-aldosterone system (RAAS) system were analyzed. Furthermore, a polygenic scoring model was established to assess individual risk of developing hypertension based on the comprehensive SNPs effects in genes related the RAAS system. Results: After controlling the impact of confounding factors, multivariate logistic regression analysis revealed that the distribution of AGT/rs5046, LRP6/rs12823243 and ACE2/rs2285666 was associated with susceptibility to essential hypertension. In genetic score model, the score > -0.225 had a higher risk, the OR (95%CI) was 1.229 (1.110, 1.362). Conclusions: To the best of our knowledge, this is the first time a hypertension risk scoring model on RAAS associated gene cluster has been constructed, which will provide a novel approach for prevention and control of essential hypertension.

Unveiling the anti-obesity potential of Kemuning (Murraya paniculata): A network pharmacology approach.

Obesity has become a global issue that affects the emergence of various chronic diseases such as diabetes mellitus, dysplasia, heart disorders, and cancer. In this study, an integration method was developed between the metabolite profile of the active compound of Murraya paniculata and the exploration of the targeting mechanism of adipose tissue using network pharmacology, molecular docking, molecular dynamics simulation, and in vitro tests. Network pharmacology results obtained with the skyline query technique using a block-nested loop (BNL) showed that histone acetyltransferase p300 (EP300), peroxisome proliferator-activated receptor gamma (PPARG), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) are potential targets for treating obesity. Enrichment analysis of these three proteins revealed their association with obesity, thermogenesis, energy metabolism, adipocytokines, fat cell differentiation, and glucose homeostasis. Metabolite profiling of M. paniculata leaves revealed sixteen active compounds, ten of which were selected for molecular docking based on drug-likeness and ADME results. Molecular docking results between PPARG and EP300 with the ten active compounds showed a binding affinity value of ≤ -5.0 kcal/mol in all dockings, indicating strong binding. The stability of the protein-ligand complex resulting from docking was examined using molecular dynamics simulations, and we observed the best average root mean square deviation (RMSD) of 0.99 Å for PPARG with trans-3-indoleacrylic acid, which was lower than with the native ligand BRL (2.02 Å). Furthermore, the RMSD was 2.70 Å for EP300 and the native ligand 99E, and the lowest RMSD with the ligand (1R,9S)-5-[(E)-2-(4-Chlorophenyl)vinyl]-11-(5-pyrimidinylcarbonyl)-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one was 3.33 Å. The in vitro tests to validate the potential of M. paniculata in treating obesity showed that there was a significant decrease in PPARG and EP300 gene expressions in 3T3-L1 mature adipocytes treated with M. paniculata ethanolic extract starting at concentrations 62.5 μg/ml and 15.625 μg/ml, respectively. These results indicate that M. paniculata can potentially treat obesity by disrupting adipocyte maturation and influencing intracellular lipid metabolism.

PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome.

We performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing's syndrome (CS) to define areas of dysregulated and druggable targets. Next-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing's disease (BADX-CD, n=8). In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1). Pathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc<-1.5) and related genes - FABP4 (l2fc<-5.5), PLIN1 (l2fc<-4.1) and ADIPOQ (l2fc<-3.3) - were significantly downregulated (p<0.005) in PBMAH. Significant downregulation of PPARG was also found in BADX-CD (l2fc<-1.9, p<0.0001) and CPA (l2fc<-1.4, p<0.0001). In vitro studies demonstrated that the PPARG activator rosiglitazone resulted in decreased cell viability in MUC1 and NCI-H295R (p<0.0001). There was also a significant reduction in the production of aldosterone, cortisol, and cortisone in NCI-H295R and in Dihydrotestosterone (DHT) in MUC1 (p<0.05), respectively. This therapeutic effect was independent of the actions of ACTH, postulating a promising application of PPARG activation in endogenous hypercortisolism.

Improving Shelf Life and Content of Unsaturated Fatty Acids in Meat of Lambs Fed a Diet Supplemented with Grape Dregs.

This study was conducted to evaluate the potential effects of dietary grape residue levels on the slaughter indicators, meat quality, meat shelf-life, unsaturated fatty acid content, and expression of fatty acid deposition genes in the muscle of lambs. Sixty 30-month-old male Dorper and Small-Tailed Han F1 hybrid lambs were assigned to a single factor complete randomized trial design and fed with four different diets including 0%, 8%, 16%, and 24% grape dregs, respectively. The findings regarding meat production efficacy in the lambs revealed substantial differences. The control group showed notably lower dressing percentage, carcass weight, net meat weight, meat percentage concerning carcass, meat-to-bone ratio, relative visceral and kidney fat mass, and rib eye area compared to the other groups (p < 0.05). Additionally, the meat shearing force of lambs fed a diet with 16% grape pomace (GP) was significantly higher than that of the 24% GP group (p < 0.05), while the 24 h meat color parameter a* value of the control group was notably higher than that of the 8% GP group (p < 0.05). In addition, compared to the control group, lambs fed with a diet containing 16% GP had higher levels of oleic acid (C18:1n-9c), linoleic acid (C18:2n-6c), behenic acid (C22:0), tricosanoic acid (C23:0), lignoceric acid (C24:0), and conjugated linoleic acid (CLA), at a ratio of ∑CLA/TFA, ∑n-6, ∑MUFA, and ∑PUFA in the longissimus dorsi muscle (p < 0.05), but the reverse case was applicable for Total Volatile Basic Nitrogen (TVB-N) content (p < 0.05). GP supplementation did not substantially affect the expression of stearoyl-CoA desaturase (SCD), peroxisome proliferator activated receptor alpha (PPARα), and peroxisome proliferator-activated receptor gamma (PPARγ) genes (p > 0.05). The findings indicated that incorporating grape dregs in the diets of fattening lambs leads to notable enhancements in meat production and the antioxidant capacity of lamb meat, and effectively extends the shelf life of the meat.

Dietary bile acids supplementation improves the growth performance and alleviates fatty liver in broilers fed a high-fat diet via improving the gut microbiota

This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3-7 d), middle stage (17-21 d), and late stage (31-35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers.

The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer's Disease-like Condition: Mechanistic Insights.

Alzheimer's disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ's neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular trajectories remain ambiguous. Thus, the objective of the current investigation was to examine the potential beneficial effects and underlying mechanisms of TQ in scopolamine (SCOP)-induced neuronal injury to mimic AD in vivo model. Thirty mice were divided into normal, SCOP, and TQ groups. The Y-maze and pole climbing tests were performed to measure memory and motor performance. Afterwards, histopathological and immunohistochemical examinations were carried out. Furthermore, peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway-related proteins and genes were detected with an emphasis on the role of miR-9. TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes, histopathological changes, modulation of the expression pattern of PPAR-γ downstream targets with a significant decrease in the deposition of amyloid beta (Aβ). TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity. Consequently, TQ may possess a potential beneficial role against AD development.

Abdominal Massage Ameliorates Inguinal Fat Accumulation via Augmentation of PPARγ Signaling in High-Fat Diet-Induced Obese Mice.

With the increase in prevalence and decrease in age of the obese population, safer weight loss methods have attracted growing attention. While abdominal massage (AM) has been clinically proven for weight loss, the mechanism thereof has yet to be elucidated. We aimed to investigate the effect of AM on abdominal fat in obese mice fed a high-fat diet and explore the possible mechanisms involved. Male C57BL/6J mice were fed a high-fat diet for 16 weeks and then treated with AM for 5 weeks; mice fed a standard diet were used as normal controls. Blood and adipose tissue, including inguinal white adipose tissue (WAT) and epididymal WAT, were collected from the mice after the intervention. We explored the mechanism of weight reduction through inguinal WAT transcriptome sequencing, quantitative real-time polymerase chain reaction (PCR) validation, and Western blot. The results revealed that AM decreased fat mass, weight, glucose, and serum lipid levels. Meanwhile, AM enhanced the expression of the peroxisome proliferator-activated receptor gamma (PPARγ) and other downstream genes (Fabp4, Acox3, Pck1, and Aqp7) in inguinal WAT. In addition, AM increased the expression of PPARγ protein. AM may promote fatty acid oxidation, lipid metabolism, and glucose homeostasis by activating the PPARγ signaling pathway in inguinal WAT, thereby exhibiting therapeutic efficacy against obesity, even in the presence of a persistent high-fat diet.

A Review of Genes Associated with Obesity Susceptibility: Findings from Association Studies

Obesity is described as the accumulation of excess body fat. Several health issues are caused by excess fat, including cancer, type 2 diabetes, and cardiovascular disease. Additionally, obesity rates among schoolchildren and young adults are rising globally, putting young people at risk of chronic diseases. Genetics, epigenetic modification, epigenomics, and environmental factors influence inheritance patterns significantly. This systematic study aimed to classify and investigate the polymorphisms of novel candidate obesity genes. Several genes have been suggested, includingat mass and obesity-associated gene (FTO), leptin gene (LEP), leptin receptor gene (LEPR), peroxisome proliferatoractivated receptor gamma gene (PPARG), melanocortin 4 receptor (MC4R), insulin-induced gene 2 (INSIG2), proprotein convertase subtilisin/kexin type 1 (PCSK1), adrenoceptor beta 2 (ADRB2), and uncoupling protein 2 (UCP2). The study’s literature review identified genes in scientific papers published in databases such as Web of Science, PubMed, Google Scholar, Embase, and others over the past three decades. There is evidence that genetic variations contribute to childhood obesity, adolescent obesity, and young adult obesity. Identifying functional differences and further defining the implicated molecularly and physiologically involved genes andpathways in efficient therapeutic approaches in fighting. Technological advances have recently demonstrated that genetic changes and mutations can be used as biological markers, risk indicators, and therapeutic targets.

Association study of selenium-related gene polymorphisms with geriatric depression in China.

Depression is a common mental health problem in older adults, but its cause remains unclear. Selenium is an essential micronutrient and a powerful antioxidant in the brain and nervous system. Several recent studies have reported a relationship between selenium levels and depression. This study aimed to investigate the relationship between 4 genes co-associated with selenium and geriatric depression. 1486 participants were included in this study from 5 communities in Ningxia Hui Autonomous Region during 2013 to 2016 in a health examination program for urban and rural residents. Polymorphisms of 4 selenium-related genes were analyzed in 1266 healthy volunteers and 220 patients with depression. The genotyping of rs2830072, rs2030324, rs6265, rs11136000, rs7982, rs10510412, rs1801282, rs1151999, rs17793951, rs709149, rs709154, and rs4135263 were performed by Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) technology. The analysis of selenium-related genes showed that there were significant differences between depression and controls for allele and genotype frequencies of peroxisome proliferator activated receptor gamma (PPARG) rs10510412, rs709149, and rs709154 (all P < .05). In this study, when adjusting for age, sex, marital status, education, and alcohol consumption, results showed that rs709149 and rs709154 were still significantly correlated with geriatric depression in the codominant, dominant, overdominant, and log-additive models. Logistic regression analysis showed that rs709149 AG or GG gene carriers were 1.630 and 1.746 times more susceptible to depression than AA gene carriers (95% CI = 1.042-2.549; 1.207-2.526). The results of this study suggest that the rs709149 polymorphism of the selenium-related gene PPARG is a genetic risk factor for depression in older adults.

Investigation on the Biological Safety and Activity of a Gluconolactone-Based Lotion for Dermocosmetic Application.

(1) Background: Cosmeceuticals are formulas enriched with active ingredients that exert efficacy on different skin molecular targets. (2) Methods: Cell viability and the absence of potential irritant risk were evaluated on keratinocytes (HaCaT), fibroblasts (NHDF), adipocytes (3T3-L1), sebocytes (PCi-SEB_CAU) and reconstructed human epidermis (RHE), respectively. Several treatments were performed to evaluate the ability of the lotion to stimulate the production of collagen and elastin, stimulate the differentiation of keratinocytes and reduce the number of senescent cells following UVB stimulation. In addition, the modulation of genes involved in the production, storage and accumulation of sebum were investigated. (3) Results: The results obtained demonstrated the biosafety of the formula in all cell lines tested. The 24-h treatment with non-cytotoxic concentrations determined an increase in the expression of the collagen (COL1A1), elastin (ELN) and involucrin (IVL) genes, while a reduction of peroxisome proliferator-activated receptor-gamma (PPARγ) gene expression and a reduction of SA-βgal-positive cells were found. Moreover, the treatment did not interfere with normal steroid 5-alpha reductase (5RDA3) gene expression levels. (4) Conclusions: Data collected demonstrated the biosafety of the lotion, the non-comedogenic property and a multi targets anti-aging effect. In particular, data collected on the booster lotion make it a valid way to counteract the pore dilatation aging related.

Evidence Linking PPARG Genetic Variants with Periodontitis and Type 2 Diabetes Mellitus in a Brazilian Population

The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene-phenotype association by assessing the subjects' biochemical and periodontal parameters, and the expression of PPARG and other immune response-related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics.

Porphyra haitanensis Polysaccharides Attenuates Blood Lipid via Gut-Liver Axis in Diet-Induced High-Fat Mesocricetus auratus through Multiple Integrated Omics.

Hyperlipidemia is currently a global public health problem severely affecting people's physical and mental health, as well as their quality of life. The present study is aimed at revealing the mechanism of Porphyra haitanensis polysaccharide (PHP) in decreasing blood lipids by acting through gut-liver axis in Mesocricetus auratus fed a high-fat diet. PHP significantly prevented increases in serum total cholesterol, triglycerides and low-density lipoprotein cholesterol, and alleviated damage to liver cells induced by a high-fat diet M. auratus, in a dose-dependent manner. PHP promotes proliferation of Muribaculaceae and Faecalibaculum, thereby enhancing the production of butyric acid both in the colon and liver, particularly high-dose PHP (HPHP). Low-dose PHP (LPHP) promotes the expression of phosphatidylcholine metabolites and fatty acid transport genes, and inhibits the expression of genes involved in fat degradation (Abhd5), adipogenesis (Me1), fatty acid synthesis (Fasn and Pnpla3), and fatty acid chain elongation (Elovl6) in the liver. However, HPHP inhibits the expression of triglyceride metabolites and promotes the expression of fatty acid transporter (CD36), fatty acid oxidation (Acacb), and peroxisome proliferator-activated receptor gamma (PPARg)genes in the liver. PHP regulates lipid metabolism through the gut microbiota, and the gut-liver axis plays an important role in its hypolipidemic effects.

Association between PPARγ, PPARGC1A, and PPARGC1B genetic variants and susceptibility of gastric cancer in an Eastern Chinese population

PurposePrevious studies showed that peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator1 family (PPARGC1A and PPARGC1B) gene single nucleotide variants (SNVs)were strongly associated with cancer susceptibility. The purpose of this study was to investigate the association of PPARγ, PPARGC1A, and PPARGC1B variants with the risk of gastric cancer (GC).Patients and methodsWe performed a case-control study of 490 GC cases and 1,476 healthy controls from eastern China. PPARγ rs1801282 C > G, rs3856806 C > T, PPARGC1A rs2970847 C > T, rs8192678 C > T and PPARGC1B rs7732671 G > C, rs17572019 G > A SNVs were selected to investigate the association between these SNVs and GC susceptibility. Genotypes of the SNVs were assessed by multiplex fluorescent PCR using a custom-by-design 48-Plex SNPscantm Kit.ResultsThe PPARγ rs1801282 SNV was associated with a decreased risk for GC (GC vs. CC: odds ratio (OR) = 0.62, 95% confidence interval (95%CI) = 0.42–0.93, adjusted P = 0.019; GC + GG vs. GG: OR = 0.63 95%CI = 0.42–0.93, adjusted P = 0.019; respectively). In addition, stratified analysis revealed that the PPARγ rs1801282 SNV was correlated with the risk of GC in subgroups of age ≥ 61, no smoking, and no alcohol consuming. We also confirmed that the PPARγ rs3856806 C > T SNV promoted the risk of GC in women. The PPARGC1A rs8192678 TT genotype decreased the susceptibility of GC in men. The PPARGC1A rs2970847 C > T SNV decreased the susceptibility of GC in the subgroup of BMI ≥ 24 kg/m2. The PPARGC1B rs7732671 G > C and rs17572019 G > A SNVs promoted the risk of GC in the subgroup of BMI ≥ 24 kg/m2.ConclusionThis study indicates that the PPARγ, PPARGC1A, and PPARGC1B SNVs may be associated with the susceptibility of GC in eastern Chinese population. Future studies with larger populations, detailed H. pylori infection status for subgroup analysis, and functional study are needed to further clarify the relationship between these SNVs and GC risk.