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International Journal of Molecular... Apr 2024"" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study,...
"" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.
Topics: Mice; Plant Extracts; Animals; 3T3-L1 Cells; Hypoglycemic Agents; Adipogenesis; Adipocytes; PPAR gamma; Anti-Obesity Agents; Obesity; Glucose Transporter Type 4; CCAAT-Enhancer-Binding Protein-alpha; alpha-Glucosidases; AMP-Activated Protein Kinases; Antioxidants; Glycoside Hydrolase Inhibitors; Crassulaceae; Lipid Metabolism; Cell Differentiation
PubMed: 38732125
DOI: 10.3390/ijms25094908 -
Animals : An Open Access Journal From... Apr 2024Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. β-sitosterol is a...
OBJECTIVE
Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. β-sitosterol is a natural product with significant hypolipidemic and cholesterol-lowering effects. However, the underlying mechanism of its action on aquatic products is not completely understood.
METHODS
A high-fat diet (HFD)-induced NAFLD zebrafish model was successfully established, and the anti-hyperlipidemic effect and potential mechanism of β-sitosterol were studied using oil red O staining, filipin staining, and lipid metabolomics.
RESULTS
β-sitosterol significantly reduced the accumulation of triglyceride, glucose, and cholesterol in the zebrafish model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differential lipid molecules in β-sitosterol mainly regulated the lipid metabolism and signal transduction function of the zebrafish model. β-sitosterol mainly affected steroid biosynthesis and steroid hormone biosynthesis in the zebrafish model. Compared with the HFD group, the addition of 500 mg/100 g of β-sitosterol significantly inhibited the expression of and in the zebrafish model by at least 50% and 25%, respectively.
CONCLUSIONS
β-sitosterol can reduce lipid accumulation in the zebrafish model of NAFLD by regulating lipid metabolism and signal transduction and inhibiting adipogenesis and lipid storage.
PubMed: 38731293
DOI: 10.3390/ani14091289 -
Journal of Lipid Research Jun 2024Adipogenesis is one of the major mechanisms for adipose tissue expansion, during which spindle-shaped mesenchymal stem cells commit to the fate of adipocyte precursors...
Adipogenesis is one of the major mechanisms for adipose tissue expansion, during which spindle-shaped mesenchymal stem cells commit to the fate of adipocyte precursors and differentiate into round-shaped fat-laden adipocytes. Here, we investigated the lipidomic profile dynamics of ex vivo-differentiated brown and white adipocytes derived from the stromal vascular fractions of interscapular brown (iBAT) and inguinal white adipose tissues. We showed that sphingomyelin was specifically enriched in terminally differentiated brown adipocytes, but not white adipocytes. In line with this, freshly isolated adipocytes of iBAT showed higher sphingomyelin content than those of inguinal white adipose tissue. Upon cold exposure, sphingomyelin abundance in iBAT gradually decreased in parallel with reduced sphingomyelin synthase 1 protein levels. Cold-exposed animals treated with an inhibitor of sphingomyelin hydrolases failed to maintain core body temperature and showed reduced oxygen consumption and iBAT UCP1 levels. Conversely, blockade of sphingomyelin synthetic enzymes resulted in enhanced nonshivering thermogenesis, reflected by elevated body temperature and UCP1 levels. Taken together, our results uncovered a relation between sphingomyelin abundance and fine-tuning of UCP1-mediated nonshivering thermogenesis.
Topics: Animals; Thermogenesis; Uncoupling Protein 1; Sphingomyelins; Mice; Male; Adipose Tissue, White; Adipose Tissue, Brown; Mice, Inbred C57BL
PubMed: 38729351
DOI: 10.1016/j.jlr.2024.100559 -
Cell Metabolism May 2024Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human...
Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.
PubMed: 38729152
DOI: 10.1016/j.cmet.2024.04.017 -
Cells Apr 2024The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy... (Review)
Review
The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy surplus, the subcutaneous white adipose tissue (WAT) is capable of expanding through the enlargement of existing adipocytes (hypertrophy), followed by de novo adipogenesis (hyperplasia), which is impaired in hypertrophic obesity. However, an impaired hyperplastic response may result from various defects in adipogenesis, leading to different WAT features and metabolic consequences, as discussed here by reviewing the results of the studies in animal models with either overexpression or knockdown of the main molecular regulators of the two steps of the adipogenesis process. Moreover, impaired WAT remodeling with aging has been associated with various age-related conditions and reduced lifespan expectancy. Here, we delve into the latest advancements in comprehending the molecular and cellular processes underlying age-related changes in WAT function, their involvement in common aging pathologies, and their potential as therapeutic targets to influence both the health of elderly people and longevity. Overall, this review aims to encourage research on the mechanisms of WAT maladaptation common to conditions of both excessive and insufficient fat tissue. The goal is to devise adipocyte-targeted therapies that are effective against both obesity- and age-related disorders.
Topics: Humans; Adipogenesis; Aging; Obesity; Adipose Tissue, White; Animals; Adipocytes
PubMed: 38727299
DOI: 10.3390/cells13090763 -
PloS One 2024Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for...
Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.
Topics: Animals; Glutathione Peroxidase; Adipocytes; MAP Kinase Signaling System; Swine; Cell Differentiation; Cell Proliferation; Adipogenesis; p38 Mitogen-Activated Protein Kinases; Muscle Fibers, Skeletal; Muscle, Skeletal
PubMed: 38722949
DOI: 10.1371/journal.pone.0298827 -
Journal of Microbiology and... May 2024Obesity is spawned by an inequality between the portion of energy consumed and the quantity of energy expended. Disease entities such as cardiovascular disease,...
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 species. Among these, 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.
Topics: PPAR gamma; Lactobacillus acidophilus; Animals; Mice; 3T3-L1 Cells; p38 Mitogen-Activated Protein Kinases; Adipogenesis; Adipocytes; Cell Differentiation; Signal Transduction; Obesity; Anti-Obesity Agents; Probiotics; Triglycerides
PubMed: 38719777
DOI: 10.4014/jmb.2402.02012 -
Life Science Alliance Jul 2024Excess abdominal fat is a sexually dimorphic risk factor for cardio-metabolic disease and is approximated by the waist-to-hip ratio adjusted for body mass index (WHR)....
Excess abdominal fat is a sexually dimorphic risk factor for cardio-metabolic disease and is approximated by the waist-to-hip ratio adjusted for body mass index (WHR). Whereas this trait is highly heritable, few causal genes are known. We aimed to identify novel drivers of WHR using systems genetics. We used two independent cohorts of adipose tissue gene expression and constructed sex- and depot-specific Bayesian networks to model gene-gene interactions from 8,492 genes. Using key driver analysis, we identified genes that, in silico and putatively in vitro, regulate many others. 51-119 key drivers in each network were replicated in both cohorts. In other cell types, 23 of these genes are found in crucial adipocyte pathways: Wnt signaling or mitochondrial function. We overexpressed or down-regulated seven key driver genes in human subcutaneous pre-adipocytes. Key driver genes and inhibited adipogenesis, whereas increased adipogenesis. increased Wnt signaling activity. In differentiated adipocytes, MIGA1 and UBR1 down-regulation led to mitochondrial dysfunction. These five genes regulate adipocyte function, and we hypothesize that they regulate fat distribution.
Topics: Humans; Adipocytes; Male; Female; Body Fat Distribution; Adipogenesis; Body Mass Index; Adult; Gene Regulatory Networks; Middle Aged; Bayes Theorem; Waist-Hip Ratio; Adipose Tissue; Wnt Signaling Pathway; Gene Expression Regulation; Systems Biology
PubMed: 38702075
DOI: 10.26508/lsa.202402603 -
Journal of Nanobiotechnology May 2024Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was...
BACKGROUND
Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration.
METHODS
Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system.
RESULTS
Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration.
CONCLUSIONS
Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.
Topics: Chemokine CXCL12; Animals; Receptors, CXCR4; Regeneration; Mice; Adipose Tissue; rhoA GTP-Binding Protein; Stem Cells; Mice, Inbred C57BL; Feedback, Physiological; Cell Movement; Cells, Cultured; Male; Signal Transduction
PubMed: 38698419
DOI: 10.1186/s12951-024-02482-9 -
Trends in Cell Biology May 2024Cilia and Wnt signaling have a complex relationship, wherein Wnt regulates cilia and, conversely, cilia may affect Wnt signaling. Recently, it was shown that Wnt... (Review)
Review
Cilia and Wnt signaling have a complex relationship, wherein Wnt regulates cilia and, conversely, cilia may affect Wnt signaling. Recently, it was shown that Wnt receptors are present in flagella, primary cilia, and multicilia, where they transmit an intraciliary signal that is independent of β-catenin. Intraciliary Wnt signaling promotes ciliogenesis, affecting male fertility, adipogenesis, and mucociliary clearance. Wnt also stimulates the beating of motile cilia, highlighting that these nanomotors, too, are chemosensory. Intraciliary Wnt signaling employs a Wnt-protein phosphatase 1 (PP1) signaling axis, involving the canonical Wnt pathway's inhibition of glycogen synthase kinase 3 (GSK3) to repress PP1 activity. Collectively, these findings support that cilia are Wnt signaling organelles, with implications for ciliopathies and cancer.
PubMed: 38697898
DOI: 10.1016/j.tcb.2024.04.001