Adipocyte最新文献

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes (T2DM). Decreased mitochondrial abundance and function were found in white adipose tissue (WAT) of T2DM patients. Therefore, promoting WAT mitochondrial biogenesis and improving adipocyte metabolism may be strategies to prevent and reverse T2DM. Salvianolic acid A (SAA) has been found to exert anti-diabetic and lipid disorder-improving effects. However whether SAA benefits mitochondrial biogenesis and function in adipose tissue is unclear. Here, we evaluated SAA's effect on mitochondrial biogenesis and function in 3T3-L1 adipocytes and investigated its potential regulatory mechanism. Results showed that SAA treatment significantly promoted the transcription and expression of peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Meanwhile, SAA treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) quantity, mitochondrial mass, and expression of mitochondrial respiratory chain enzyme complexes III and complex IV. These enhancements were accompanied by enhanced phosphorylation of AMPK and ACC and were suppressed by Compound C, a specific AMPK inhibitor. Furthermore, SAA treatment improved adipocytes mitochondrial respiration and stimulated ATP generation. These findings indicate that SAA exerts a potential therapeutic capacity against adipocytes mitochondrial dysfunction in diabetes by activating the AMPK-PGC-1α pathway.

Adipose tissue (AT) dysfunctions, such as adipocyte hypertrophy, macrophage infiltration and secretory adiposopathy (low plasma adiponectin/leptin, A/L, ratio), associate with metabolic disorders. However, no study has compared the relative contribution of these markers to cardiometabolic risk in women of varying age and adiposity. Body composition, regional AT distribution, lipid-lipoprotein profile, glucose homeostasis and plasma A and L levels were determined in 67 women (age: 40-62 years; BMI: 17-41 kg/m²). Expression of macrophage infiltration marker CD68 and adipocyte size were measured from subcutaneous abdominal (SCABD) and omental (OME) fat. AT dysfunction markers correlated with most lipid-lipoprotein levels. The A/L ratio was negatively associated with fasting insulinemia and HOMA-IR, while SCABD or OME adipocyte size and SCABD CD68 expression were positively related to these variables. Combination of tertiles of largest adipocyte size and lowest A/L ratio showed the highest HOMA-IR. Multiple regression analyses including these markers and TAG levels revealed that the A/L ratio was the only predictor of fasting insulinemia and HOMA-IR. The contribution of the A/L ratio was superseded by adipose cell size in the model where the latter replaced TAGs. Finally, leptinemia was a better predictor of IR than adipocyte size and the A/L ratio in our participants sample.

Type 2 Diabetes (T2D) is associated with impaired vascularization of adipose tissue (AT) . IL8, GROα and IL15 are pro-angiogenic myokines, secreted at elevated levels by T2D myotubes. We explored the direct impact of these myokines on AT vascularization. AT explants from subjects with T2D and without diabetes (non-diabetic, ND) were treated with rIL8, rGROα and rIL15 in concentrations equal to those in conditioned media (CM) from T2D and ND myotubes, and sprout formation evaluated. Endothelial cells (EC) were isolated from T2D and ND-AT, treated with rGROα and tube formation evaluated. Finally, we investigated the involvement of MMP-2 and -9 in vascularization. ND and T2D concentrations of IL8 or IL15   caused similar stimulation of sprout formation in ND- and T2D-AT. GROα exerted a similar effect in ND-AT. When T2D-AT explants were exposed to GROα, sprout formation in response to T2D concentrations was reduced compared to ND. Exposure of EC from T2D-AT to GROα at T2D concentrations resulted in reduced tube formation. Reduced responses to GROα in T2D-AT and EC were also seen for secretion of MMP-2 and -9. The data indicate that skeletal muscle can potentially regulate AT vascularization, with T2D-AT having impairments in sensitivity to GROα, while responding normally to IL8 and IL15.

Bariatric surgery (BS) is a dependable method for managing obesity and metabolic diseases, however, the regulatory processes of lipid metabolism are still not well elucidated. Differentially expressed genes (DEGs) were analysed through three transcriptomic datasets of GSE29409, GSE59034 and GSE72158 from the GEO database regarding subcutaneous adipose tissue (SAT) after BS, and 37 DEGs were identified. The weighted gene co-expression network analysis (WGCNA), last absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms further screened four key genes involved in the regulation of STMN2, SFRP4, APOE and MXRA5. The GSE53376 dataset was used to further confirm the differential expression of SFRP4, APOE and MXRA5 in the postoperative period. GSEA analysis reveals activation of immune-related regulatory pathways after surgery. Finally, the silencing of MXRA5 was found by experimental methods to affect the expression of PPARγ and CEBPα during the differentiation of preadipocytes, as well as to affect the formation of lipid droplets. In conclusion, SAT immunoregulation was mobilized after BS, while MXRA5 was involved in the regulation of lipid metabolism.

Brown adipose tissue (BAT) generates heat through non-shivering thermogenesis, and increasing BAT amounts or activity could facilitate obesity treatment and provide metabolic benefits. In mice, BAT has been reported in perirenal, thoracic and cranial sites. Here, we describe new pelvic and lower abdominal BAT depots located around the urethra, internal reproductive and urinary tract organs and major lower pelvic blood vessels, as well as between adjacent muscles where the upper hind leg meets the abdominal cavity. Immunohistochemical, western blot and PCR analyses revealed that these tissues expressed BAT markers such as uncoupling protein 1 (UCP1) and CIDEA, but not white adipose markers, and β3-adrenergic stimulation increased UCP1 amounts, a classic characteristic of BAT tissue. The newly identified BAT stores contained extensive sympathetic innervation with high mitochondrial density and multilocular lipid droplets similar to interscapular BAT. BAT repositories were present and functional neonatally, and showed developmental changes between the neonatal and adult periods. In summary, several new depots showing classical BAT characteristics are reported and characterized in the lower abdominal/pelvic region of mice. These BAT stores are likely significant metabolic regulators in the mouse and some data suggests that similar BAT depots may also exist in humans.

In this study, we retrospectively evaluated the data of 901 men undergoing ultrasonography-guided systematic prostate biopsy between March 2013 and May 2022. Adipose features, including periprostatic adipose tissue (PPAT) thickness and subcutaneous fat thickness, were measured using MRI before biopsy. Prediction models of all PCa and clinically significant PCa (csPCa) (Gleason score higher than 6) were established based on variables selected by multivariate logistic regression and prediction nomograms were constructed. Patients with PCa had higher PPAT thickness (4.64 [3.65-5.86] vs. 3.54 [2.49-4.51] mm, p < 0.001) and subcutaneous fat thickness (29.19 [23.05-35.95] vs. 27.90 [21.43-33.93] mm, p = 0.013) than those without PCa. Patients with csPCa had higher PPAT thickness (4.78 [3.80-5.88] vs. 4.52 [3.80-5.63] mm, p = 0.041) than those with non-csPCa. Adding adipose features to the prediction models significantly increased the area under the receiver operating characteristics curve for the prediction of all PCa (0.850 vs. 0.819, p < 0.001) and csPCa (0.827 vs. 0.798, p < 0.001). Based on MRI-measured adipose features and clinical parameters, we established two nomograms that were simple to use and could improve patient selection for prostate biopsy in Chinese population.

Obesity-associated type 2 diabetes (DM) leads to adipose tissue dysfunction. Lumican is a proteoglycan implicated in obesity, insulin resistance (IR), and adipocyte dysfunction. Using human visceral adipose tissue (VAT) from subjects with and without DM, we studied lumican effects on adipocyte function. Lumican was increased in VAT and adipocytes in DM. Lumican knockdown in adipocytes decreased lipolysis and improved adipogenesis and insulin sensitivity in VAT adipocytes in DM, while treatment with human recombinant lumican increased lipolysis and impaired insulin-sensitivity in an ERK-dependent manner. We demonstrate that lumican impairs adipocyte metabolism, partially via ERK signalling, and is a potential target for developing adipose tissue-targeted therapeutics in DM.

Predictors of overall epicardial adipose tissue deposition have been found to vary between males and females. Whether similar sex differences exist in epicardial fat cell morphology is currently unknown. This study aimed to determine whether epicardial fat cell size is associated with different clinical measurements in males and females. Fat cell sizes were measured from epicardial, paracardial, and appendix adipose tissues of post-mortem cases (N= 118 total, 37 females). Epicardial, extra-pericardial, and visceral fat volumes were measured by computed tomography from a subset of cases (N= 70, 22 females). Correlation analyses and stepwise linear regression were performed to identify predictors of fat cell size in males and females. Median fat cell sizes in all depots did not differ between males and females. Body mass index (BMI) and age were independently predictive of epicardial, paracardial, and appendix fat cell sizes in males, but not in females. Epicardial and appendix fat cell sizes were associated with epicardial and visceral fat volumes, respectively, in males only. In females, paracardial fat cell size was associated with extra-pericardial fat volume, while appendix fat cell size was associated with BMI only. No predictors were associated with epicardial fat cell size in females at the univariable or multivariable levels. To conclude, no clinical measurements were useful surrogates of epicardial fat cell size in females, while BMI, age, and epicardial fat volume were independent, albeit weak, predictors in males only.

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP), regulate growth and metabolic pathways. Here, we asked if serum levels of these factors are altered with overweight/obesity and if this is related to adipose tissue (AT) expression and/or increased fat mass. Furthermore, we hypothesized that expression of GHR, IGF-1 and IGFBP-3 is associated with AT function. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio obesity-related elevations were detectable until early puberty. Circulating levels did not correlate with AT expression of these factors, which was decreased with overweight/obesity. Independent from obesity, expression of GHR, IGF-1 and IGFBP-3 was related to AT dysfunction,and increased insulin levels. Serum GHBP was associated with liver fat percentage and transaminase levels. We conclude that obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased AT mass and elevations in GHBP are more closely related to liver status in children. The diminished AT expression of these factors with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state.

Soft tissue defects caused by adipose tissue loss can result in various conditions such as lipodystrophy in congenital diseases, trauma secondary to ageing, and mastectomy in breast cancer; fat grafting is commonly performed to restore these defects. Although various enrichment strategies have been studied, novel therapeutics that are cost-effective, safe, technologically easy to manufacture, and minimally invasive are required. In this study, we identified a novel peptide derived from plasminogen, named plasminogen-derived peptide-1 (PLP-1), which showed adipogenic differentiation potential and led to an increase in the expression levels of adiponectin, C1Q and collagen domain containing protein, fatty acid-binding protein 4, and CCAAT/enhancer-binding protein-alpha. In vivo experiments confirmed an increase in the rate of adipocyte differentiation and the expression levels of CD31 in the PLP-1-treated mice groups. These results suggested that PLP-1 plays an important role in promoting the differentiation of preadipocytes and may be useful for developing therapeutic approaches to treat adipose tissue defects.