PPARγ Expression Research Articles

Glucagon-like peptide-1 analog liraglutide reduces fat deposition in chicken adipocytes

Previously, we reported that glucagon-like peptide-1 (GLP-1) and its analog liraglutide could inhibit fat de novo synthesis in the liver and reduce abdominal fat accumulation in broiler chickens. Nevertheless, the impact of GLP-1 on adipocyte fat deposition remains enigmatic. This study aimed to investigate the effects of GLP-1, via its analog liraglutide, on chicken chicken adipocytes in vitro. Chemical assays, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were employed to assess the proliferation, differentiation, and fat deposition of chicken adipocytes. Our findings indicated that liraglutide significantly suppressed cell proliferation and promoted preadipocyte differentiation in comparison to the control group. This was evidenced by elevated triglyceride (TG) content and upregulated mRNA expression of lipogenesis-related enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), as well as regulators including peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element binding protein-1 (SREBP1) and CCAAT/enhancer binding protein α (CEBPα). In mature adipocytes, liraglutide attenuated fat deposition by inhibiting fat de novo synthesis, evidenced by decreased mRNA expression of ACC, FAS, PPARγ, C/EBPα, and SREBP1, and concurrent upregulation of phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated ACC (p-ACC). This resulted in reduced accumulation of lipid droplets and TG content in mature adipocytes. Collectively, our findings indicate that liraglutide suppresses the proliferation of preadipocytes, enhances their differentiation, and concurrently inhibits de novo lipogenesis in mature adipocytes. This observation offers profound insights into the mechanisms that underlie liraglutide's anti-adipogenic effects, which could have significant implications for the treatment of obesity in broiler chickens.

Furan-based chalcone protects β-cell damage and improves glucose uptake in alloxan-induced zebrafish diabetic model via influencing Peroxisome Proliferator-Activated Receptor agonists (PPAR-γ) signaling

Diabetes mellitus, a major global health concern, is emerging as the primary human disease in the twenty-first century, with beta cell damage and dysfunction playing a critical role, particularly in type 2 diabetes. Inflammation and oxidative stress are critical in beta cell damage associated with type 2 diabetes. Current anti-diabetic drugs frequently fail to achieve intended efficacy and are associated with side effects, necessitating novel treatments that target the underlying pathophysiology. Chalcones have gained popularity due to their varied biological activity. In this study, we use an alloxan-induced beta cell damage zebrafish model to evaluate the potential anti-inflammatory and beta cell protective properties of DKO3 ((E)-1-(5-methylfuran-2-yl)-3-(3-nitrophenyl) prop-2-en-1-one), a synthetic chalcone. DKO3 exhibits dose-dependent anti-inflammatory and α-glucosidase activity in vitro. DKO3 reduced oxidative stress, restored antioxidant enzyme levels, decreased lipid peroxidation and cellular damage, inhibited cellular apoptosis, and regulated proinflammatory cytokine levels. It prevented alloxan-induced beta cell damage, increased PPAR-γ expression, and influenced insulin-sensitive genes such as SIRT1, GLUT2, GSK3, and INSA. These findings underscore DKO3's potential therapeutic utility in managing diabetes and related inflammatory conditions.

Sexual Dimorphism's impact on adipogenesis: A three-dimensional in vitro model treated with 17β-estradiol and testosterone

Using a three-dimensional (3-D) in vitro culture model, we report the dose dependent effect of 17β-estradiol and testosterone on the adipogenic differentiation and maturation of human adipose derived stem cells (hASCs) obtained from female and male patients. Considering sexual dimorphism, we expected male and female adipocytes to respond differently to the sex steroids. Both male and female hASC spheroids were exposed to 100 nM and 500 nM of 17β-estradiol and testosterone either at the beginning of the adipogenic maturation (Phase I) to discourage intracellular triglyceride accumulation or exposed after adipogenic maturation (Phase II) to reduce the intracellular triglyceride accumulation. The results show that 17β-estradiol leads to a dose dependent reduction in intracellular triglyceride accumulation in female hASC spheroids compared to the both untreated and testosterone-treated cells. Affirming our hypothesis, 17β-estradiol prevented intracellular triglyceride accumulation during Phase I, while it stimulated lipolysis during Phase II. PPAR-γ and adiponectin gene expression also reduced upon 17β-estradiol treatment in female cells. Interestingly, 17β-estradiol and testosterone had only a modest effect on the male hASC spheroids. Collectively, our findings suggest that 17β-estradiol can prevent fat accumulation in adipocytes during early and late stages of maturation in females.

Electroacupuncture reduces oxidative stress response and improves secondary injury of intracerebral hemorrhage in rats by activating the peroxisome proliferator-activated receptor-γ/nuclear factor erythroid2-related factor 2/γ-glutamylcysteine synthetase pathway.

Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.

Xiaozhi formula attenuates non-alcoholic fatty liver disease by regulating lipid metabolism via activation of AMPK and PPAR pathways

BackgroundXiaozhi formula (XZF) is a practical Chinese herbal formula for the treatment of non-alcoholic fatty liver disease (NAFLD), which possesses an authorized patent certificate issued by the State Intellectual Property Office of China (ZL202211392355.0). However, the underlying mechanism by which XZF treats NAFLD remains unclear. PurposeThis study aimed to explore the main component of XZF and its mechanism of action in NAFLD treatment. MethodsUHPLC-Q-Orbitrap HRMS was used to identify the components of the XZF. A high-fat diet (HFD)-induced NAFLD mouse model was used to demonstrate the effectiveness of XZF. Body weight, liver weight, and white fat weight were recorded to evaluate the therapeutic efficacy of XZF. H&E and Oil Red O staining were applied to observe the extent of hepatic steatosis. Liver damage, lipid metabolism, and glucose metabolism were detected by relevant assay kits. Moreover, the intraperitoneal insulin tolerance test and the intraperitoneal glucose tolerance test were employed to evaluate the efficacy of XZF in insulin homeostasis. Hepatocyte oxidative damage markers were detected to assess the efficacy of XZF in preventing oxidative stress. Label-free proteomics was used to investigate the underlying mechanism of XZF in NAFLD. RT-qPCR was used to calculate the expression levels of lipid metabolism genes. Western blot analysis was applied to detect the hepatic protein expression of AMPK, p-AMPK, PPARɑ, CPT1, and PPARγ. Results120 compounds were preliminarily identified from XZF by UHPLC-Q-Orbitrap HRMS. XZF could alleviate HFD-induced obesity, white adipocyte size, lipid accumulation, and hepatic steatosis in mice. Additionally, XZF could normalize glucose levels, improve glucolipid metabolism disorders, and prevent oxidative stress damage induced by HFD. Furthermore, the proteomic analysis showed that the major pathways in fatty acid metabolism and the PPAR signaling pathway were significantly impacted by XZF treatment. The expression levels of several lipolytic and β-oxidation genes were up-regulated, while the expression of fatty acid synthesis genes declined in the HFD + XZF group. Mechanically, XZF treatment enhanced the expression of p-AMPK, PPARɑ, and CPT-1 and suppressed the expression of PPARγ in the livers of NAFLD mice, indicating that XZF could activate the AMPK and PPAR pathways to attenuate NALFD progression. ConclusionXZF could attenuate NAFLD by moderating lipid metabolism by activating AMPK and PPAR signaling pathways.

Identification of PPARG as key gene to link coronary atherosclerosis disease and rheumatoid arthritis via microarray data analysis.

Inflammation is the common pathogenesis of coronary atherosclerosis disease (CAD) and rheumatoid arthritis (RA). Although it is established that RA increases the risk of CAD, the underlining mechanism remained indefinite. This study seeks to explore the molecular mechanisms of RA linked CAD and identify potential target gene for early prediction of CAD in RA patients. The study utilized five raw datasets: GSE55235, GSE55457, GSE12021 for RA patients, and GSE42148 and GSE20680 for CAD patients. Gene Set Enrichment Analysis (GSEA) was used to investigate common signaling pathways associated with RA and CAD. Then, weighted gene co-expression network analysis (WGCNA) was performed on RA and CAD training datasets to identify gene modules related to single-sample GSEA (ssGSEA) scores. Overlapping module genes and differentially expressed genes (DEGs) were considered as co-susceptible genes for both diseases. Three hub genes were screened using a protein-protein interaction (PPI) network analysis via Cytoscape plug-ins. The signaling pathways, immune infiltration, and transcription factors associated with these hub genes were analyzed to explore the underlying mechanism connecting both diseases. Immunohistochemistry and qRT-PCR were conducted to validate the expression of the key candidate gene, PPARG, in macrophages of synovial tissue and arterial walls from RA and CAD patients. The study found that Fc-gamma receptor-mediated endocytosis is a common signaling pathway for both RA and CAD. A total of 25 genes were screened by WGCNA and DEGs, which are involved in inflammation-related ligand-receptor interactions, cytoskeleton, and endocytosis signaling pathways. The principal component analysis(PCA) and support vector machine (SVM) and receiver-operator characteristic (ROC) analysis demonstrate that 25 DEGs can effectively distinguish RA and CAD groups from normal groups. Three hub genes TUBB2A, FKBP5, and PPARG were further identified by the Cytoscape software. Both FKBP5 and PPARG were downregulated in synovial tissue of RA and upregulated in the peripheral blood of CAD patients and differential mRNAexpreesion between normal and disease groups in both diseases were validated by qRT-PCR.Association of PPARG with monocyte was demonstrated across both training and validation datasets in CAD. PPARG expression is observed in control synovial epithelial cells and foamy macrophages of arterial walls, but was decreased in synovial epithelium of RA patients. Its expression in foamy macrophages of atherosclerotic vascular walls exhibits a positive correlation (r = 0.6276, p = 0.0002) with CD68. Our findings suggest that PPARG may serve as a potentially predictive marker for CAD in RA patients, which provides new insights into the molecular mechanism underling RA linked CAD.

Protective effect of cellulose and soluble dietary fiber from Saccharina japonica by-products on regulating inflammatory responses, gut microbiota, and SCFAs production in colitis mice

This study aimed to investigate the physicochemical properties of soluble dietary fiber (SDF) and cellulose enriched in Saccharina japonica by-products and to evaluate their anti-colitis effects. The water-holding capacity (WHC), swelling capacity (SC), cation exchange capacity (CEC), and antioxidant properties of SDF were superior to cellulose. The ΔH of SDF and cellulose was 340.73 J/g and 134.56 J/g, and the average particle size of them was 43.858 μm and 97.350 μm. The viscosity of SDF was positively correlated with the content. SEM revealed that the microstructure of SDF was porous, whereas cellulose was folded. SDF contained seven monosaccharides such as mannuronic acid and mannose, while cellulose had a single glucose composition. It was also shown that both SDF and cellulose reversed the pathological process of colitis by inhibiting weight loss, preventing colon injury, balancing oxidative stress, and regulating the level of inflammation, with the optimal dose being 1.5 g/kg. The difference was that SDF inhibited the expression of NF-кB and TNF-α, while cellulose up-regulated the expression of PPAR-γ and IL-10. Additionally, SDF could more positively control the expression of ZO-1, whereas cellulose was superior in improving the expression of Occludin. Interestingly, SDF could restore the structure of norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group to ameliorate ulcerative colitis (UC), whereas cellulose mainly regulated the abundance of norank_f_Muribaculaceae, Faecalibaculum, Bacteroides and unclassified_f__Lachnospiraceae. The production of short-chain fatty acids (SCFAs) was also found to be restored by SDF and cellulose. Overall, SDF and cellulose can be considered important dietary components for treating and preventing UC.

Pioglitazone enhances cisplatin’s impact on triple-negative breast cancer: Role of PPARγ in cell apoptosis

Peroxisome proliferator-activated receptor-gamma (PPARγ) has been recently shown to play a role in many cancers. The breast tissue of triple-negative breast cancer (TNBC) patients were found to have a significantly lower expression of PPARγ than the other subtypes. Furthermore, PPARγ activation was found to exert anti-tumor effects by inhibiting cell proliferation, differentiation, cell growth, cell cycle, and inducing apoptosis. To start with, we performed a bioinformatic analysis of data from OncoDB, which showed a lower expression pattern of PPARγ in different cancer types. In addition, high expression of PPARγ was associated with better breast cancer patient survival. Therefore, we tested the impact of pioglitazone, a PPARγ ligand, on the cytotoxic activity of cisplatin in the TNBC cell line. MDA-MB-231 cells were treated with either cisplatin (40 μM) with or without pioglitazone (30 or 60 μM) for 72 h. The MTT results showed a significant dose-dependent decrease in cell viability as a result of using cisplatin and pioglitazone combination compared with cisplatin alone. In addition, the protein expression of Bcl-2, a known antiapoptotic marker, decreased in the cells treated with cisplatin and pioglitazone combination at doses of 40 and 30 μM, respectively. On the other hand, cleaved- poly-ADP ribose polymerase (PARP) and -caspase-9, which are known as pro-apoptotic markers, were upregulated in the combination group compared with the solo treatments. Taken together, the addition of pioglitazone to cisplatin further reduced the viability of MDA-MB-231 cells and enhanced apoptosis compared with chemotherapy alone.

The effect of quercetin on adipogenesis, lipolysis, and apoptosis in 3T3-L1 adipocytes: The role of SIRT1 pathways.

Lipotoxicity, caused by adipocyte triglyceride over-accumulation, contributes to obesity-related comorbidities such as hypertension, type 2 diabetes, coronary heart disease, respiratory dysfunction, and osteoarthritis. This study focuses on determining how sirtuin-1 (SIRT-1) mediates quercetin's (QCT) effect on 3T3-L1 adipocytes. Key aspects of this study include preventing adipogenesis, inducing lipolysis, and stimulating adipocyte apoptosis. 3T3-L1 adipocytes underwent treatment with varying QCT doses, lipopolysaccharide (LPS), and the SIRT-1 inhibitor EX-527, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide [MTT] assay for cell viability assessment. Furthermore, quantitative real-time polymerase chain reaction measured mRNA expression levels of adipogenesis markers (fatty acid synthase [FASN] and peroxisome proliferator-activated receptor gamma [PPARγ]), lipolysis markers (adipose triglyceride lipase [ATGL] and hormone-sensitive lipase [HSL]), and apoptosis markers (B-cell lymphoma2 [Bcl-2], Bcl-2 Associated -X-protein [BAX] and Caspase-3). The data showed that LPS+QCT significantly reduced cell viability in a dose- and time-dependent manner, unaffected by LPS+QCT+EX-527. Treatment with LPS+QCT did not affect FASN and PPARγ expression but significantly increased ATGL and HSL mRNA expression compared with LPS alone. Interestingly, EX-527 reversed the effects of LPS+QCT on lipogenesis and lipolysis markers completely. QCT enhanced apoptosis in a SIRT-1 independent pattern. The data suggest that QCT suppresses adipogenesis while increasing lipolysis via SIRT-1. However, QCT's effects on apoptosis appear to be independent of SIRT-1. These findings provide further evidence for QCT's effects on adipocytes, particularly its interaction with SIRT-1.

Effects of fermented cottonseed meal inclusions on growth performance, serum biochemical parameters and hepatic lipid metabolism of geese during 28–70 d of age

The aim of this study was to investigate the effects of solid-state fermented cottonseed meal (FCSM) inclusion levels on the growth performance, serum biochemical parameters and hepatic lipid metabolism in geese from 28 to 70 d of age. A total of 288 28‐d‐old male geese were randomly divided into 4 treatments with FCSM levels of 0, 5, 15 and 25% including 0, 22.74, 67.33, 111.27 mg FG/kg diet, respectively. Each treatment contained 6 replicates and 12 birds per replicate. Treatments of FCSM inclusions from 0 to 25% had no effect on growth rate and feed intake in geese during d 28-70. The F/G ratio was increased (P < 0.05) in geese fed the diet with 25% FCSM compared with birds fed the diet with 0% FCSM. Treatment with 25% FCSM levels had no effect on the contents of TC, TG, HDL-C, LDL-C, but increased (P < 0.05) AST and ALT activities in serum of geese at d 70. Treatment with 25% FCSM increased the contents of FG, HDL-C, TC, C18:2n6, C20:4n6 and PUFA and decreased (P < 0.05) the contents of NEFA, SFA, MUFA in liver compared with treatment of 0% FCSM inclusion. Additionally, treatment with 25% FCSM decreased (P < 0.05) the PPARα, AMPK and LXR mRNA expression related to lipid deposition, and increased (P < 0.05) PPARγ and ACC mRNA expression related to lipolysis in liver compared with birds fed the diet with 0% FCSM. Overall, treatment with 0-15% FCSM (<=67.33 mg FG/kg diet) had no adverse effects on the growth performance and lipid metabolism of geese. However, treatment fed 25% FCSM (111.27 mg FG/kg diet) decreased feed efficiency and promoted hepatic lipid deposition associated with the alteration of related gene expression in geese at 28-70 d of age.

Pyrogallol protects against influenza A virus-triggered lethal lung injury by activating the Nrf2-PPAR-γ-HO-1 signaling axis.

Pyrogallol, a natural polyphenol compound (1,2,3-trihydroxybenzene), has shown efficacy in the therapeutic treatment of disorders associated with inflammation. Nevertheless, the mechanisms underlying the protective properties of pyrogallol against influenza A virus infection are not yet established. We established in this study that pyrogallol effectively alleviated H1N1 influenza A virus-induced lung injury and reduced mortality. Treatment with pyrogallol was found to promote the expression and nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Notably, the activation of Nrf2 by pyrogallol was involved in elevating the expression of PPAR-γ, both of which act synergistically to enhance heme oxygenase-1 (HO-1) synthesis. Blocking HO-1 by zinc protoporphyrin (ZnPP) reduced the suppressive impact of pyrogallol on H1N1 virus-mediated aberrant retinoic acid-inducible gene-I-nuclear factor kappa B (RIG-I-NF-κB) signaling, which thus abolished the dampening effects of pyrogallol on excessive proinflammatory mediators and cell death (including apoptosis, necrosis, and ferroptosis). Furthermore, the HO-1-independent inactivationof janus kinase 1/signal transducers and activators of transcription (JAK1/STATs) and the HO-1-dependent RIG-I-augmented STAT1/2 activation were both abrogatedby pyrogallol, resulting in suppression of the enhanced transcriptional activity of interferon-stimulated gene factor 3 (ISGF3) complexes, thus prominently inhibiting the amplification of the H1N1 virus-induced proinflammatory reaction and apoptosis in interferon-beta (IFN-β)-sensitized cells. The study provides evidence that pyrogallol alleviates excessive proinflammatory responses and abnormal cell death via HO-1 induction, suggesting it could be a potential agent for treating influenza.

CsHscB Derived from a Liver Fluke Clonorchis sinensis Ameliorates Cholestatic Hepatic Fibrosis in a Mouse Model of Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammatory fibrosis usually involving the whole biliary tree. However, there are very limited treatment options to treat this disease. Our previous study found a lipid-protein rCsHscB from a liver fluke - Clonorchis sinensis, which had full capacities of immune regulation. Therefore, we investigated the role of rCsHscB in a mouse model of sclerosing cholangitis induced by xenobiotic 3,5- diethoxycarbonyl-1,4-dihydrocollidine (DDC) to explore whether this protein had potential therapeutic value for PSC. Mice were fed 0.1% DDC for 4 weeks and treated with CsHscB (30 μg/mouse, intraperitoneal injection, once every 3 days); the control group was given an equal amount of PBS or CsHscB under normal diet conditions. All the mice were sacrificed at 4 weeks for the evaluation of biliary proliferation, fibrosis, and inflammation. rCsHscB treatment attenuated DDC-induced liver congestion and enlargement and significantly decreased the upregulation of serum AST and ALT levels. The administration of rCsHscB to DDC-fed mice significantly decreased cholangiocyte proliferation and pro-inflammatory cytokine production compared to mice fed with DDC alone. Also, rCsHscB treatment showed a decreased expression of α-SMA in the liver and other markers of liver fibrosis (Masson staining, Hydroxyproline content, and collagen deposit). More interestingly, DDC-fed mice treated with rCsHscB showed a significant up-regulation of PPAR-γ expression, which was similar to control mice, indicating the involvement of PPAR-γ signaling in the protective action of rCsHscB. Overall, our data show that rCsHscB attenuates the progression of cholestatic fibrosis induced by DDC and supports the potential for manipulating the parasite-derived molecule to treat certain immune-mediated disorders.

Bone Morphogenetic Protein 2 Enhances Porcine Beige Adipogenesis via AKT/mTOR and MAPK Signaling Pathways.

Bone morphogenetic protein 2 (BMP2) has been reported to regulate adipogenesis, but its role in porcine beige adipocyte formation remains unclear. Our data reveal that BMP2 is significantly induced at the early stages of porcine beige adipocyte differentiation. Additionally, supplementing rhBMP2 during the early stages, but not the late stages of differentiation, significantly enhances porcine SVF adipogenesis, thermogenesis, and proliferation. Furthermore, compared to the empty plasmid-transfected-SVFs, BMP2-overexpressed SVFs had the enhanced lipid accumulation and thermogenesis, while knockdown of BMP2 in SVFs exhibited the opposite effect. The RNA-seq of the above three types of cells revealed the enrichment of the annotation of thermogenesis, brown cell differentiation, etc. In addition, the analysis also highlights the significant enrichment of cell adhesion, the MAPK cascade, and PPARγ signaling. Mechanistically, BMP2 positively regulates the adipogenic and thermogenic capacities of porcine beige adipocytes by activating PPARγ expression through AKT/mTOR and MAPK signaling pathways.

Inhibitory Effect of Prickly Ash (Zanthoxylum bungeanum) Seed Kernel Oil on Lipid Metabolism of Grass Carp (Ctenopharyngodon idellus) in High-Fat Diet

To investigate the effect of prickly ash (Zanthoxylum bungeanum) seed kernel oil (PASO) on the lipid metabolism of grass carp (Ctenopharyngodon idellus) under a high-fat diet, PASO were added into two lipid-level (4 g/kg and 8 g/kg) diets to form four isonitrogenous diets: soybean oil (SO), PASO, high-fat soybean oil (HSO), and high-fat prickly ash seed oil (HPASO). A total of 216 healthy grass carp (9.43 ± 0.82 g) were randomly divided into four groups and fed with the four diets, respectively, for 56 days. The result showed that the viscerosomatic index (VSI) and the content of the crude lipid in the hepatopancreas and muscle was significantly higher by oil levels (p &lt; 0.05). The linolenic acid content in the body of the fish significantly increased in PASO and HPASO compared to that in SO and HSO (p &lt; 0.05). The fatty acid composition of the hepatopancreas, intraperitoneal fat, and muscle in four dietary groups was significantly similar to the fatty acid composition in the diets (p &lt; 0.05). More significant fat infiltration and nuclear translocation in the hepatopancreas of fish was found in the HSO group but was decreased in the HPASO group. The adipocyte size in the intraperitoneal fat tissue in the PASO group was significantly lower than that in the SO group (p &lt; 0.05). The relative mRNA expression of the lipogenesis-related genes ppar-γ, cebp-α, and srebp-1c was significantly down-regulated in the PASO group compared with the SO group (p &lt; 0.05), and the mRNA expression of lipolysis-related genes ppar-α and cpt-1 were significantly up-regulated in the PASO group (p &lt; 0.05). In conclusion, dietary PASO showed the function of reducing lipid accumulation in the fish. This reduction might be attributed to the inhibition of the lipogenesis-related genes and the stimulation of the lipolysis-related genes, which were probably modulated by the high content of linolenic acid in PASO.

Anti-Obesity Effect of Lactobacillus acidophilus DS0079 (YBS1) by Inhibition of Adipocyte Differentiation through Regulation of p38 MAPK/PPARγ Signaling.

Obesity is spawned by an inequality between the portion of energy consumed and the quantity of energy expended. Disease entities such as cardiovascular disease, arteriosclerosis, hypertension, and cancer, which are correlated with obesity, influence society and the economy. Suppression of adipogenesis, the process of white adipocyte generation, remains a promising approach for treating obesity. Oil Red O staining was used to differentiate 3T3-L1 cells for screening 20 distinct Lactobacillus species. Among these, Lactobacillus acidophilus DS0079, referred to as YBS1, was selected for further study. YBS1 therapy decreased 3T3-L1 cell development. Triglyceride accumulation and mRNA expression of the primary adipogenic marker, peroxisome proliferator-activated receptor gamma (PPARγ), including its downstream target genes, adipocyte fatty acid binding protein 4 and adiponectin, were almost eliminated. YBS1 inhibited adipocyte differentiation at the early stage (days 0-2), but no significant difference was noted between the mid-stage (days 2-4) and late-stage (days 4-6) development. YBS1 stimulated the activation of p38 mitogen-activated protein kinase (p38 MAPK) during the early stages of adipogenesis; however, this effect was eliminated by the SB203580 inhibitor. The data showed that YBS1 administration inhibited the initial development of adipocytes via stimulation of the p38 MAPK signaling pathway, which in turn controlled PPARγ expression. In summary, YBS1 has potential efficacy as an anti-obesity supplement and requires further exploration.

Danggui Shaoyao powder improves hepatic lipid metabolism in atherosclerosis mice via PPARγ-LXRα-ABCA1 pathway regulation

ObjectiveTo observe the effects of Danggui Shaoyao powder (DSP) on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor (PPARγ)-liver X receptor (LXRα)-adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) pathway regulation. MethodsEight C57BL/6J male mice were selected as the control group, and 24 ApoE−/− male mice were randomly divided into the atherosclerosis model (AS) group, atorvastatin calcium (AC) group, and DSP group (n = 8 each group). To establish an AS model, ApoE−/− mice were fed a high-fat diet for 16 weeks. Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining. Triglyceride (TG), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were determined in the livers using a single-reagent GPO-PAP method. Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver. ResultsAfter 16 weeks of a high-fat diet, ApoE−/− mice showed more Oil Red O staining in the aorta and liver compared to the CONT group. Compared to the AS group, the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees. Furthermore, DSP significantly reduced the hepatic lipid area in ApoE−/− mice (P < .001) and decreased the levels of TG, TC, and LDL-C in liver (P < .001, P = .027, P < .001, respectively). DSP also significantly increased the levels of PPARγ, LXRα, ABCA1, and ABCG1 mRNA expression, as well as the PPARγ, LXRα, ABCA1, and ABCG1 protein expression in liver. ConclusionDSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Arthrospira platensis F&M-C265 reduces cardiometabolic risk factors in rats fed a high fat diet

Clinical studies indicate that Arthrospira platensis (A. platensis) mitigates cardiometabolic risk factors, but the underlying mechanisms are very elusive. To fill this gap, Sprague-Dowley rats were fed either AIN-76 normal diet (5 % corn oil) or high-fat (HF; 30 % lard + 3 % corn oil) or HF + 5 % A. platensis F&M-C256 diet for 3 months. A. platensis F&M-C256 decreased blood triglycerides and total cholesterol, systolic and diastolic pressure and enhanced the expression of thermogenesis-related genes Prdm16, Dio2, PPARγ, Ucp1 and Lpl in visceral adipose tissue, compared to HF-diet. A. platensis reduced ANGPTL3 plasma levels and hepatic steatosis, prevented periaortic adipose tissue hypertrophy and increased aortic eNOS expression. These data provide some mechanistic evidence about the beneficial effects of A. platensis observed in human studies. Further controlled trials are needed to verify the clinical usefulness of A. platensis supplementation against metabolic disorders, to select the dosing regimens and the subgroup of patients with likelihood of benefit.

The potential efficacy of Artemisia anuua L. extract nanoparticles in mitigating obesity-related-metabolic complications in hypercaloric diet-fed rats

ABSTRACT Obesity-related health problems are worsening in various societies worldwide. Artemisia anuua L. (AA) has distinctive health benefits, including anti-inflammatory, antioxidant, and insulin-sensitizing properties. Nanoformulation of herbal extracts is a new approach to enhance the bioavailability of natural products. This study aimed to evaluate the efficacy of AA extract, either the conventional extract (AAE) or its nano-form (AAEN), in modulating obesity-related metabolic complications in hypercaloric (high-fat/high-sucrose) diet-induced obese rats. Forty-eight rats were divided into two groups fed either a basal or hypercaloric diet for twelve weeks. Starting from the eighth week, each main group was subdivided into three subgroups and treated orally with either saline, AAE, or AAEN until the end of the experiment. Both AAE and AAEN exerted antiadipogenic effects. They reduced body weight and epididymal fat, mitigated dyslipidemia, improved glucose utilization and insulin resistance, reduced hyperleptinemia, increased serum adiponectin, and decreased oxidative stress and inflammatory markers. These results were mediated by regulating SIRT-1, PGC-1α, SREBP-1, PPAR-γ, FAS, LPL, IRS 1, and GLUT4 gene expression, suggesting an effect of AA on de novo lipogenesis and glucose utilization. The AAEN produced more expressive ameliorating effects than the conventional extract. AAE administration ameliorated the obesity-associated metabolic complications induced by feeding a hypercaloric diet, implying that this extract may be used as a complementary treatment option for obesity and its metabolic consequences. The antiadipogenic effectiveness of AAE was enhanced by its nanoformulation, suggesting that the nanoparticle system can be applied to boost other herbal medicine effectiveness.

In Vitro Comparative Analysis of the Effect and Structure-Based Influencing Factors of Flavonols on Lipid Accumulation.

Flavonols represented by quercetin have been widely reported to have biological activities of regulating lipid metabolism. However, the differences in flavonols with different structures in lipid-lowering activity and the influencing factors remain unclear. In this study, the stability, transmembrane uptake ratio, and lipid metabolism regulation activities of 12 flavonol compounds in the 3T3-L1 cell model were systematically compared. The results showed that kaempferide had the highest cellular uptake ratio and the most potent inhibitory effect on adipogenesis at a dosing concentration of 20 μM, followed by isorhamnetin and kaempferol. They inhibited TG accumulation by more than 65% and downregulated the expression of PPARγ and SREBP1c by more than 60%. The other four aglycones, including quercetin, did not exhibit significant activity due to the structural instability in the cell culture medium. Meanwhile, five quercetin glucosides were quite stable but showed a low uptake ratio that no obvious activity was observed. Correlation analysis also showed that for 11 compounds except galangin, the activity was positively correlated with the cellular uptake ratio (p < 0.05, r = 0.6349). These findings may provide a valuable idea and insight for exploring the structure-based activity of flavonoids at the cellular level.

A comparative assessment of reference genes in mouse brown adipocyte differentiation and thermogenesis in vitro

ABSTRACT Adipogenic differentiation and thermogenesis in brown adipose tissue (BAT) undergo dynamic processes, altering phenotypes and gene expressions. Proper reference genes in gene expression analysis are crucial to mitigate experimental variances and ensure PCR efficacy. Unreliable reference genes can lead to erroneous gene expression quantification, resulting in data misinterpretation. This study focused on identifying suitable reference genes for mouse brown adipocyte research, utilizing brown adipocytes from the Ucp1-luciferase ThermoMouse model. Comparative analysis of gene expression data under adipogenesis and thermogenesis conditions was conducted, validating 13 housekeeping genes through various algorithms, including DeltaCq, BestKeeper, geNorm, Normfinder, and RefFinder. Tbp and Rer1 emerged as optimal references for Ucp1 and Pparg expression in brown adipogenesis, while Tbp and Ubc were ideal for the expression analysis of these target genes in thermogenesis. Conversely, certain conventional references, including Actb, Tubb5, and Gapdh, proved unstable as reference genes under both conditions. These findings stress the critical consideration of reference gene selection in gene expression analysis within specific biological systems to ensure accurate conclusions.