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Foods (Basel, Switzerland) Jun 2024has a long history of cultivation in Asia and is widely used in food production for its unique aroma, which has important cultural and economic values. It is rich in...
has a long history of cultivation in Asia and is widely used in food production for its unique aroma, which has important cultural and economic values. It is rich in flavonoids with diverse pharmacological properties, such as antioxidant, anti-tumor, and anti-lipid activities. However, little is known regarding the effects of flavonoid extract (OFFE) on adipogenesis and pre-adipocyte transdifferentiation. Herein, this research aimed to investigate the effect of OFFE on the differentiation, adipogenesis, and beiging of 3T3-L1 adipocytes and to elucidate the underlying mechanism. Results showed that OFFE inhibited adipogenesis, reduced intracellular reactive oxygen species levels in mature adipocytes, and promoted mitochondrial biogenesis as well as beiging/browning in 3T3-L1 adipocytes. This effect was accompanied by increased mRNA and protein levels of the brown adipose-specific marker gene , and the upregulation of the expression of , , and . Moreover, the research observed a dose-dependent reduction in the mRNA expression of adipogenic genes (, , , and ) with increasing concentrations of OFFE. Additionally, OFFE activated the AMPK signaling pathway to inhibit adipogenesis. These findings elucidate that OFFE has an inhibitory effect on adipogenesis and promotes browning in 3T3-L1 adipocytes, which lays the foundation for further investigation of the lipid-lowering mechanism of OFFE in vivo in the future.
PubMed: 38928836
DOI: 10.3390/foods13121894 -
International Journal of Molecular... Jun 2024Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying...
Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying the IL-6 exacerbation in the adipose tissue remains unclear. There is general agreement that TNF-α and stearate concentrations are mildly elevated in adipose tissue in the state of obesity. We hypothesize that TNF-α and stearate co-treatment induce the increased expression of IL-6 in mouse adipocytes. We therefore aimed to determine IL-6 gene expression and protein production by TNF-α/stearate treated adipocytes and investigated the mechanism involved. To test our hypothesis, 3T3-L1 mouse preadipocytes were treated with TNF-α, stearate, or TNF-α/stearate. IL-6 gene expression was assessed by quantitative real-time qPCR. IL-6 protein production secreted in the cell culture media was determined by ELISA. Acetylation of histone was analyzed by Western blotting. Il6 region-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac) was determined by ChIP-qPCR. 3T3-L1 mouse preadipocytes were co-challenged with TNF-α and stearate for 24 h, which led to significantly increased IL-6 gene expression (81 ± 2.1 Fold) compared to controls stimulated with either TNF-α (38 ± 0.5 Fold; = 0.002) or stearate (56 ± 2.0 Fold; = 0.013). As expected, co-treatment of adipocytes with TNF-α and stearate significantly increased protein production (338 ± 11 pg/mL) compared to controls stimulated with either TNF-α (28 ± 0.60 pg/mL; = 0.001) or stearate (53 ± 0.20 pg/mL, = 0.0015). Inhibition of histone acetyltransferases (HATs) with anacardic acid or curcumin significantly reduced the IL-6 gene expression and protein production by adipocytes. Conversely, TSA-induced acetylation substituted the stimulatory effect of TNF-α or stearate in their synergistic interaction for driving IL-6 gene expression and protein production. Mechanistically, TNF-α/stearate co-stimulation increased the promoter-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac), rendering a transcriptionally permissive state that favored IL-6 expression at the transcriptional and translational levels. Our data represent a TNF-α/stearate cooperativity model driving IL-6 expression in 3T3-L1 cells via the H3K9/18Ac-dependent mechanism, with implications for adipose IL-6 exacerbations in obesity.
Topics: Animals; Mice; Histones; Interleukin-6; 3T3-L1 Cells; Tumor Necrosis Factor-alpha; Acetylation; Adipocytes; Stearic Acids; Gene Expression Regulation
PubMed: 38928498
DOI: 10.3390/ijms25126776 -
International Journal of Molecular... Jun 2024Adipose tissue, a central player in energy balance, exhibits significant metabolic flexibility that is often compromised in obesity and type 2 diabetes (T2D).... (Review)
Review
Adipose tissue, a central player in energy balance, exhibits significant metabolic flexibility that is often compromised in obesity and type 2 diabetes (T2D). Mitochondrial dysfunction within adipocytes leads to inefficient lipid handling and increased oxidative stress, which together promote systemic metabolic disruptions central to obesity and its complications. This review explores the pivotal role that mitochondria play in altering the metabolic functions of the primary adipocyte types, white, brown, and beige, within the context of obesity and T2D. Specifically, in white adipocytes, these dysfunctions contribute to impaired lipid processing and an increased burden of oxidative stress, worsening metabolic disturbances. Conversely, compromised mitochondrial function undermines their thermogenic capabilities, reducing the capacity for optimal energy expenditure in brown adipocytes. Beige adipocytes uniquely combine the functional properties of white and brown adipocytes, maintaining morphological similarities to white adipocytes while possessing the capability to transform into mitochondria-rich, energy-burning cells under appropriate stimuli. Each type of adipocyte displays unique metabolic characteristics, governed by the mitochondrial dynamics specific to each cell type. These distinct mitochondrial metabolic phenotypes are regulated by specialized networks comprising transcription factors, co-activators, and enzymes, which together ensure the precise control of cellular energy processes. Strong evidence has shown impaired adipocyte mitochondrial metabolism and faulty upstream regulators in a causal relationship with obesity-induced T2D. Targeted interventions aimed at improving mitochondrial function in adipocytes offer a promising therapeutic avenue for enhancing systemic macronutrient oxidation, thereby potentially mitigating obesity. Advances in understanding mitochondrial function within adipocytes underscore a pivotal shift in approach to combating obesity and associated comorbidities. Reigniting the burning of calories in adipose tissues, and other important metabolic organs such as the muscle and liver, is crucial given the extensive role of adipose tissue in energy storage and release.
Topics: Diabetes Mellitus, Type 2; Humans; Obesity; Mitochondria; Energy Metabolism; Animals; Adipocytes; Adipose Tissue; Oxidative Stress; Thermogenesis
PubMed: 38928386
DOI: 10.3390/ijms25126681 -
International Journal of Molecular... Jun 2024Adipose tissue is conventionally recognized as a metabolic organ responsible for storing energy. However, a proportion of adipose tissue also functions as a thermogenic... (Review)
Review
Adipose tissue is conventionally recognized as a metabolic organ responsible for storing energy. However, a proportion of adipose tissue also functions as a thermogenic organ, contributing to the inhibition of weight gain and prevention of metabolic diseases. In recent years, there has been significant progress in the study of thermogenic fats, particularly brown adipose tissue (BAT). Despite this progress, the mechanism underlying thermogenesis in beige adipose tissue remains highly controversial. It is widely acknowledged that beige adipose tissue has three additional thermogenic mechanisms in addition to the conventional UCP1-dependent thermogenesis: Ca cycling thermogenesis, creatine substrate cycling thermogenesis, and triacylglycerol/fatty acid cycling thermogenesis. This paper delves into these three mechanisms and reviews the latest advancements in the molecular regulation of thermogenesis from the molecular genetic perspective. The objective of this review is to provide readers with a foundation of knowledge regarding the beige fats and a foundation for future research into the mechanisms of this process, which may lead to the development of new strategies for maintaining human health.
Topics: Thermogenesis; Humans; Adipocytes, Beige; Animals; Uncoupling Protein 1; Adipose Tissue, Brown; Energy Metabolism; Calcium; Fatty Acids; Triglycerides; Adipose Tissue, Beige
PubMed: 38928011
DOI: 10.3390/ijms25126303 -
Cancers Jun 2024Endometrial cancer (EC) includes various histologic types, with estrogen-dependent endometrioid carcinoma being the most common. Obesity significantly increases the risk... (Review)
Review
Endometrial cancer (EC) includes various histologic types, with estrogen-dependent endometrioid carcinoma being the most common. Obesity significantly increases the risk of developing this type, especially in postmenopausal women, due to elevated estrogen production by adipocytes. This review examines the impact of weight loss from different interventions on reducing obesity-related risk factors for endometrioid EC. A systematic review and meta-analysis were conducted on three weight loss interventions: bariatric surgery, pharmacotherapy, and lifestyle changes. The effects of these interventions on inflammatory biomarkers (CRP, TNF-α, IL-6) and hormones (leptin, estrogen) were analyzed. Data from controlled studies were pooled to assess the significance of weight loss in reducing these biomarkers. Despite heterogeneity, bariatric surgery resulted in an overall 25.8% weight reduction, outperforming lifestyle and pharmacotherapy interventions. Weight loss reduced CRP levels by 33.5% and IL-6 levels by 41.9%. TNF-α levels decreased by 13% with percent weight loss over 7%. Leptin levels also decreased significantly, although the exact weight loss percentage was not statistically significant. Weight loss effectively reduces proinflammatory markers and hormones associated with increased risk of endometrioid EC. The strengths of this review include a comprehensive examination of different weight-loss interventions and a large pool of participants. However, limitations include high heterogeneity among studies and only 43% of the participants being postmenopausal. Limited data on sex hormones and racial disparities underscore the need for further research.
PubMed: 38927903
DOI: 10.3390/cancers16122197 -
Bioengineering (Basel, Switzerland) Jun 2024The purpose of the current study was to elucidate the physiological roles of intraocularly present fatty acid-binding protein 4 (FABP4). Using four representative...
The purpose of the current study was to elucidate the physiological roles of intraocularly present fatty acid-binding protein 4 (FABP4). Using four representative intraocular tissue-derived cell types, including human non-pigmented ciliary epithelium (HNPCE) cells, retinoblastoma (RB) cells, adult retinal pigment epithelial19 (ARPE19) cells and human ocular choroidal fibroblast (HOCF) cells, the intraocular origins of FABP4 were determined by qPCR analysis, and the intracellular functions of FABP4 were investigated by seahorse cellular metabolic measurements and RNA sequencing analysis using a specific inhibitor for FABP4, BMS309403. Among these four different cell types, FABP4 was exclusively expressed in HOCF cells. In HOCF cells, both mitochondrial and glycolytic functions were significantly decreased to trace levels by BMS309403 in a dose-dependent manner. In the RNA sequencing analysis, 67 substantially up-regulated and 94 significantly down-regulated differentially expressed genes (DEGs) were identified in HOCF cells treated with BMS309403 and those not treated with BMS309403. The results of Gene Ontology enrichment analysis and ingenuity pathway analysis (IPA) revealed that the DEGs were most likely involved in G-alpha (i) signaling, cAMP-response element-binding protein (CREB) signaling in neurons, the S100 family signaling pathway, visual phototransduction and adrenergic receptor signaling. Furthermore, upstream analysis using IPA suggested that NKX2-1 (thyroid transcription factor1), HOXA10 (homeobox A10), GATA2 (gata2 protein), and CCAAT enhancer-binding protein A (CEBPA) were upstream regulators and that NKX homeobox-1 (NKX2-1), SFRP1 (Secreted frizzled-related protein 1) and TREM2 (triggering receptor expressed on myeloid cells 2) were causal network master regulators. The findings in this study suggest that intraocularly present FABP4 originates from the ocular choroid and may be a critical regulator for the cellular homeostasis of non-adipocyte HOCF cells.
PubMed: 38927820
DOI: 10.3390/bioengineering11060584 -
Bioengineering (Basel, Switzerland) May 2024Biological aging is defined as a progressive decline in tissue function that eventually results in cell death. Accelerated biologic aging results when the telomere... (Review)
Review
Role of Mesenchymal Stem/Stromal Cells (MSCs) and MSC-Derived Extracellular Vesicles (EVs) in Prevention of Telomere Length Shortening, Cellular Senescence, and Accelerated Biological Aging.
Biological aging is defined as a progressive decline in tissue function that eventually results in cell death. Accelerated biologic aging results when the telomere length is shortened prematurely secondary to damage from biological or environmental stressors, leading to a defective reparative mechanism. Stem cells therapy may have a potential role in influencing (counteract/ameliorate) biological aging and maintaining the function of the organism. Mesenchymal stem cells, also called mesenchymal stromal cells (MSCs) are multipotent stem cells of mesodermal origin that can differentiate into other types of cells, such as adipocytes, chondrocytes, and osteocytes. MSCs influence resident cells through the secretion of paracrine bioactive components such as cytokines and extracellular vesicles (EVs). This review examines the changes in telomere length, cellular senescence, and normal biological age, as well as the factors contributing to telomere shortening and accelerated biological aging. The role of MSCs-especially those derived from gestational tissues-in prevention of telomere shortening (TS) and accelerated biological aging is explored. In addition, the strategies to prevent MSC senescence and improve the antiaging therapeutic application of MSCs and MSC-derived EVs in influencing telomere length and cellular senescence are reviewed.
PubMed: 38927760
DOI: 10.3390/bioengineering11060524 -
Genes Jun 2024Peroxisome proliferator-activated receptor γ (PPARG) has various splicing variants and plays essential roles in the regulation of adipocyte differentiation and...
Peroxisome proliferator-activated receptor γ (PPARG) has various splicing variants and plays essential roles in the regulation of adipocyte differentiation and lipogenesis. However, little is known about the expression pattern and effect of the PPARG on milk fat synthesis in the buffalo mammary gland. In this study, we found that only and of the splicing variant were expressed in the buffalo mammary gland. Amino acid sequence characterization showed that the proteins encoded by and are endonuclear non-secreted hydrophilic proteins. Protein domain prediction found that only the -encoded protein had PPAR ligand-binding domains (NR_LBD_PPAR), which may lead to functional differences between the two splices. RNA interference (RNAi) and the overexpression of and in buffalo mammary epithelial cells (BMECs) were performed. Results showed that the expression of fatty acid synthesis-related genes (, , , , , ) was significantly modified ( < 0.05) by the RNAi and overexpression of and . All kinds of FAs detected in this study were significantly decreased ( < 0.05) after RNAi of or . Overexpression of or significantly decreased ( < 0.05) the SFA content, while significantly increased ( < 0.05) the UFA, especially the MUFA in the BMECs. In conclusion, there are two splicing variants expressed in the BMECs that can regulate FA synthesis by altering the expression of diverse fatty acid synthesis-related genes. This study revealed the expression characteristics and functions of the gene in buffalo mammary glands and provided a reference for further understanding of fat synthesis in buffalo milk.
Topics: Animals; Buffaloes; PPAR gamma; Mammary Glands, Animal; Female; Epithelial Cells; Alternative Splicing; Fatty Acids; Protein Isoforms; Milk
PubMed: 38927715
DOI: 10.3390/genes15060779 -
Genes Jun 2024The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in...
The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in chickens are still poorly understood. is differentially expressed in abdominal preadipocytes and 10-day differentiated adipocytes in chickens, but its role in regulating chicken adipogenesis has not been reported. In this study, the function of in chicken abdominal preadipocytes was investigated. is significantly upregulated during abdominal adipocyte differentiation. The overexpression of upregulated the expression of adipogenic marker genes and proliferation-related genes, and promoted the proliferation of adipocytes and the accumulation of triglycerides. The knockdown of downregulated the expression of adipogenic marker genes and proliferation-related genes, inhibited the proliferation of adipocytes, and impaired the accumulation of triglycerides in adipocytes. In addition, was differentially expressed in abdominal preadipocytes and mature adipocytes, and was significantly positively correlated with the expression of . Interference with inhibits the expression of adipogenic marker genes and proliferation-related genes. The data supported the notion that promotes the differentiation of chicken abdominal adipocytes by cis-regulating the expression of . This study identified the role of in the differentiation and proliferation of chicken adipocytes, providing a potential target for improving abdominal adipogenesis in chickens.
Topics: Animals; Adipocytes; Chickens; Adipogenesis; RNA, Long Noncoding; Cell Differentiation; Cell Proliferation
PubMed: 38927694
DOI: 10.3390/genes15060758 -
Genes May 2024With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich...
With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes , , , and , associated with adipose deposition. Pathway analysis highlighted enrichment in adipose deposition-related pathways, including PPAR, insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as and . Single-cell transcriptome data pointed to the specific expression of and in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake's potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement.
Topics: Animals; Juglans; Swine; Transcriptome; Animal Feed; Adipose Tissue; Gene Expression Profiling; Adipocytes
PubMed: 38927603
DOI: 10.3390/genes15060667