Adipocyte最新文献

Obesity triggers chronic low-grade inflammation contributing to cardiovascular and metabolic diseases. Over-release of adipokines and pro-inflammatory mediators by white adipose tissue (WAT) enhances inflammation through a feedforward loop involving endothelial and immune cells, promoting atherosclerosis. Our previous studies showed that in vivo gene transfer of the longevity-associated variant (LAV) of BPIFB4 restores endothelial and cardiac function and reduces systemic inflammation in mouse models. Here we investigated the anti-inflammatory potential of orally administered recombinant rhLAV-BPIFB4 in ApoE-/- mice fed a high-fat diet to elucidate its role in modulating endothelial dysfunction primed by adipose tissue inflammation. We studied n = 5 ApoE-/- mice on standard diet (SD), n = 5 (VEH-HFD) and n = 6 (LAV-HFD) ApoE-/- mice fed high-fat diet without or with rhLAV-BPIFB4 protein. Primary pre-adipocyte cultures were established from epididymal WAT to evaluate CD45+CD38+ leukocyte infiltration, inflammatory profile of pre-adipocytes, and ex vivo effects of conditioned media on vessels. Oral administration of rhLAV-BPIFB4 in ApoE-/- mice fed high-fat diet dampens atherosclerosis by preserving endothelial integrity and reducing ICAM+ and CD68+ cell infiltration. Despite unchanged adiposity, systemically rhLAV-BPIFB4 reduces pro-inflammatory cytokines (IL-1α/β, TNF-α, IL-6) while mildly increasing IL-10 levels. Supernatants from pre-adipocytes treated with rhLAV-BPIFB4 demonstrate similar anti-inflammatory cytokine profiles. Conditioned media from rhLAV-treated eWAT ex vivo restores endothelial function in dysfunctional arteries (VEH-HFD vs LAV-HFD, ***p < 0.001). Collectively our data show that targeting adipocyte-associated inflammation, LAV-BPIFB4 emerges as a promising therapeutic strategy to counteract endothelial dysfunction in obesity.

As obesity rates continue to rise, it is important that we can effectively study adipose tissue to understand its physiological contribution in individuals with obesity. Unfortunately, due to the fragility and buoyancy of adipose tissue, culture remains challenging. Ex vivo culture of tissue explants is possible, however after 48 hours explants often display declining viability, increased inflammation, and de-differentiation. Other common approaches include differentiation of preadipocytes and adipocyte isolation by enzymatic dissociation, however these methods are time-consuming and fail to recapitulate the structure and cellular network within adipose tissue. Given these shortcomings, we developed a novel explant culture method using polydimethylsiloxane (PDMS) flow chambers attached to a micro peristaltic pump. This approach reduces air interface while enabling media perfusion, time-resolved measurements of secreted factors, and easy incorporation of treatments. Using our chambers, we assessed viability with resazurin and lactate dehydrogenase (LDH) assays, physiology by measuring glycerol release, architecture by confocal imaging, and retention of adipose gene expression by qPCR. Explants remained viable for over 72 hours. Resazurin reduction was at 84 ± 9% of baseline, and LDH release remained low. Isoproterenol treatment resulted in 2.7 ± 0.5-fold increased glycerol release, while insulin returned release to baseline. Confocal imaging showed preserved architecture, while qPCR of human tissue with insulin and dexamethasone supplementation showed maintained expression of PPARG and FABP4 over 72 hours. Overall, our results suggest PDMS flow chambers are a suitable method for adipose explant culture that requires minimal processing, making this system a viable option for translational research.

Immune cell infiltration into adipose tissue (AT) is a key factor in type 2 diabetes (T2DM). However, research on the impact of fat distribution on immune cells and immune responses in women is still lacking. This study used enrichment, protein-protein interaction network, immune cell infiltration, and correlation analysis to compare the similarities and differences between the transcriptome data of visceral AT (VAT) and subcutprotein-proteinaneous AT (SAT) obtained from the omprehensive database of gene expression in women with non-T2DM and T2DM. DEGs with the same biological function in two types of ATs often exhibited different expression trends. SharedVAT-specific and SAT-specific hub genes were mainly associated with transcription factors, monocyte-macrophage markers, and chemokines, respectively. Immune cells affected by both AT types included monocytes, granulocytes, T and B lymphocytes, and NK cells. VAT affected more immune cells, mainly myeloid cells. Shared hub genes in VAT correlated positively with M1 macrophages, suggesting pro-inflammatory effects, while those in SAT correlated negatively with M1 macrophages and lymphocytes, suggesting anti-inflammatory effects. This study provides a theoretical basis for further understanding the correlation between AT and T2DM in women.

Considering the adverse effects of marketed drugs, we isolated and analysed topse fish oil (FO) in this study for the first time and examined its effect on obesity. Topse, scientifically known as Polynemus paradiseus, is a common fish species found in the maritime environment of the West Bengal region. To explore the role of marine P. paradiseus FO in alleviating obesity-related metabolic disorders in vivo model. Twenty-four male BALB/c mice with a standard body weight of 18.2 ± 2.1 g were taken and randomly divided into four groups: control group (C), normal chow feeding; obese control (OC), high fat diet (HFD) feeding; Treatment I (T-I) and Treatment II (T-II) group received 200 mg and 400 mg crude oil/kg body weight/day by gavage along with HFD. Here, we examined the effects of P. paradiseus oil on white adipose tissue (WAT) weight, lipid profiles, blood glucose, and adipokine expression levels in the OC group compared to the treated groups to evaluate the anti-obesity effects of FO. Compared to the HFD-induced OC group, the treated obese mice group (T-I and T-II) showed a significant reduction in body weight, Body Mass Index (BMI), and serum lipid profiles following the application of FO. The FO-treated HFD-induced obese mice group showed a moderate reduction in obesity and inflammatory-related adipocytokines compared to the OC group. Topse FO was enhanced with a large amount of essential fatty acids (FAs) and it might be administered as a dietary supplement to prevent obesity.

Obesity is associated with chronic inflammation and disruptions in cellular homeostasis, including impaired autophagy in adipose tissue. This study aimed to investigate the key mitophagy markers in the adipose tissue of individuals with obesity, compared to healthy controls. A total of 60 participants were enrolled, comprising 30 individuals with obesity and 30 healthy controls. Adipose tissue and peripheral blood samples were collected from all participants. Biochemical analyses included measurement of tumor necrosis factor-alpha (TNF-α), leptin, succinate dehydrogenase (SDH), and oxidative stress markers. Gene expression levels of mitophagy-related genes, PARK2, PINK1, and BNIP3L were assessed using quantitative real-time PCR. Additionally, immunohistochemistry was performed to evaluate BNIP3L protein levels in adipose tissue. Compared to the control group, individuals with obesity showed significantly elevated levels of TNF-α and SDH, along with evidence of oxidative stress. Moreover, the expression of PARK2, PINK1, and BNIP3L was significantly upregulated in the obesity group, suggesting increased mitophagy activity in adipose tissue. These findings indicate heightened inflammation and upregulation of mitophagy pathways in the adipose tissue of individuals with obesity. The upregulation of mitophagy-related genes seems to indicate a possible activation of mitophagy-associated pathways in the altered metabolic and inflammatory environment of obesity.

White and brown adipocytes differ markedly in lipid composition and metabolic function. White adipocytes primarily serve as energy storage depots, whereas brown adipocytes are mitochondria-rich and specialized for thermogenesis. However, the lipidomic profiles of white-like (WLAs) and brown-like adipocytes (BLAs) differentiated from human mesenchymal stem cells (MSCs) remain incompletely characterized. Human adipose-derived MSCs were differentiated into WLAs and BLAs. Lipid fractions were isolated and analysed by gas-liquid chromatography. Fatty acid composition data were used to calculate indices of stearoyl-CoA desaturase-1 (SCD1) activity, elongation, and ω6 synthesis. Compared to MSCs, BLAs showed consistently elevated oleate (≥4.2-fold) and stearate (≥2.3-fold), along with reduced palmitate (≤-20%) and linoleate (≤-28%) across phospholipid, triglyceride, and free fatty acid fractions. WLAs versus MSCs showed similar trends, with oleate increasing up to 15-fold and palmitate decreasing by 67-82% depending on the lipid class. SCD1 activity and elongation indices were elevated in WLAs (SCD1: up to 4.7-fold; elongation: up to 28-fold). The ω6 synthesis index was also increased in triglyceride and free fatty acid fractions of WLAs (≥3.3-fold), but markedly suppressed in BLAs (≤-88.7%). WLAs and BLAs differentiated from MSCs exhibit distinct lipid profiles and inferred enzymatic activity patterns, reflecting their respective capacities for lipid storage and metabolic flexibility. These findings provide a foundation for future translational research aimed at targeting adipose tissue in obesity and metabolic diseases.

Stem cell-based bone tissue engineering offers a promising approach for treating oral and cranio-maxillofacial bone defects. This study investigated the role of Atoh8, a key regulator in various cells, in the osteogenic potential of adipose-derived stem cells (ADSCs). ADSCs transfected with small interfering RNA (siRNA) targeting Atoh8 were evaluated for proliferation, migration, adhesion, and osteogenic capacity. In vivo, 20 SD rats were used to assess bone regeneration using Atoh8-knockdown ADSC sheets, with new bone formation quantified via micro-CT and histological analysis. Atoh8 knockdown in vitro reduced ADSC proliferation and migration but enhanced osteogenic differentiation and upregulation of osteogenic-related factors. This approach improved bone healing in rat defect models, accelerating repair both in vitro and in vivo. The findings underscore the clinical potential of ADSCs in bone tissue engineering and elucidate Atoh8's regulatory role in ADSC osteogenesis, providing a novel therapeutic strategy for enhancing bone regeneration through targeted modulation of stem cell differentiation pathways.

Obesity remains a global health challenge, underscoring the need for more effective therapeutic strategies. Recent evidence highlights the central role of adipose tissue autophagy in metabolic homoeostasis, with its dysregulation contributing to obesity-related pathophysiology. MicroRNAs (miRNAs) have emerged as critical regulators of autophagy in adipocytes, influencing differentiation, lipid metabolism, and systemic energy balance. This review synthesizes current knowledge on how specific miRNAs modulate autophagic activity in adipose tissue and discusses their functional impact on adipocyte biology. Based on the accumulated evidence, we conclude that targeting miRNA-mediated autophagy pathways holds significant therapeutic potential for obesity and related metabolic disorders. Future research should focus on translating these mechanistic insights into targeted interventions, overcoming delivery challenges, and advancing miRNA-based therapeutics towards clinical application.

Objective: Brown adipose tissue activation is a potential anti-obesity strategy. N⁷-methylguanosine (m⁷G) modification is a novel RNA epigenetic modification, but its role in adipose metabolism remains unexplored.

Methods: Male mice were fed a high-fat diet (HFD), followed by PCR array screening. Gain-of-function experiments and TRAC-seq were employed to explore WDR4 function.

Result: A Mouse Epigenetic Modification Enzymes PCR Array revealed that WDR4 expression showed the most pronounced downregulation in HFD mice. Overexpression of WDR4 in 3T3-L1 cells and primary adipocytes significantly increased UCP1 expression and suppressed lipid droplet formation, and enhanced mitophagy as evidenced by mitochondrial ultrastructure, autophagic vesicles, and LC3 expression. Suppression of mitophagy using 3-MA and bafilomycin A1 attenuated WDR4-induced adipocyte browning. WDR4 overexpression enhanced translational activity and reshaped the tRNA m⁷G methylome in 3T3-L1 adipocytes, specifically induced 38 unique tRNA m⁷G modification sites, and increasing cleavage scores of multiple tRNAs. GSE229240 dataset revealed that WDR4 mutation significantly reduced translation efficiency of 195 genes enriched in the TGF-β signalling , including BMP8B. Knockdown of BMP8B partially counteracted WDR4-mediated mitophagy.

Conclusion: WDR4 promotes adipocyte browning by enhancing BMP8B translation through tRNA m⁷G modification, revealing a novel m⁷G epitranscriptomic mechanism with therapeutic potential for obesity.

Adipocyte hypertrophy is a critical contributor to obesity-induced inflammation and insulin resistance. This study employed a human adipocyte hypertrophy model to investigate the adipokine release, inflammatory responses, and the intracellular singling pathways. Hypertrophic adipocytes exhibited increased lipid content and lipolysis, a decline of anti-inflammatory adipokine adiponectin release and an increase of pro-inflammatory adipokine leptin release compared to mature adipocytes. Moreover, TNFα and LPS exacerbated the decrease in adiponectin secretion by hypertrophic adipocytes while promoting the secretion of leptin, MCP-1 and IL-6, which is associated with impaired activation of p38 and JNK MAPK and persistent activation of ERK and IκBα in hypertrophic adipocytes. These altered adipokine secretions and inflammatory responses within hypertrophic adipocytes may contribute to adipocyte dysfunction in human obesity.