Adipocyte最新文献

The cytokine interleukin (IL)-27 has been reported to induce thermogenesis in white adipocytes. However, it remains unknown whether IL-27-mediated adipocyte energy dissipation is paralleled by an elevated energy supply from lipids and/or carbohydrates. We hypothesized that IL-27 increases lipolysis and glucose uptake in white adipocytes, thereby providing substrates for thermogenesis. Unexpectedly, we found that treatment of 3T3-L1 adipocytes with IL-27 reduced intra- and extracellular free fatty acid (FFA) concentrations and that phosphorylation of hormone-sensitive lipase (HSL) was not affected by IL-27. These results were confirmed in subcutaneous white adipocytes. Further, application of IL-27 to 3T3-L1 adipocytes increased intracellular triglyceride (TG) content but not mitochondrial ATP production nor expression of enzymes involved in beta-oxidation indicating that elevated esterification rather than oxidation causes FFA disappearance. In addition, IL-27 significantly increased GLUT1 protein levels, basal glucose uptake as well as glycolytic ATP production, suggesting that increased glycolytic flux due to IL-27 provides the glycerol backbone for TG synthesis. In conclusion, our findings suggest IL-27 increases glucose uptake and TG deposition in white adipocytes.

Alterations of the extracellular matrix contribute to adipose tissue dysfunction in metabolic disease. We studied the role of matrix density in regulating human adipocyte phenotype in a tunable hydrogel culture system. Lipid accumulation was maximal in intermediate hydrogel density of 5 weight %, relative to 3% and 10%. Adipogenesis and lipid and oxidative metabolic gene pathways were enriched in adipocytes in 5% relative to 3% hydrogels, while fibrotic gene pathways were enriched in 3% hydrogels. These data demonstrate that the intermediate density matrix promotes a more adipogenic, less fibrotic adipocyte phenotype geared towards increased lipid and aerobic metabolism. These observations contribute to a growing literature describing the role of matrix density in regulating adipose tissue function.

Exercise is a universally acknowledged and healthy way to reducing body weight. However, the roles and mechanisms of exercise on metabolism of adipose tissue remain largely unclear. Adipose tissues include white adipose tissue (WAT), brown adipose tissue (BAT) and beige adipose tissue (BeAT). The main function of WAT is to store energy, while the BAT and BeAT can generate heat and consume energy. Therefore, promotion of BAT activation and WAT browning contributes to body weight loss. To date, many studies have suggested that exercise exerts the potential regulatory effects on BAT activation and WAT browning. In the present review, we compile the evidence for the regulatory effects of exercise on BAT activation and WAT browning and summarize the possible mechanisms whereby exercise modulates BAT activation and WAT browning, including activating sympathetic nervous system (SNS) and promoting the secretion of exerkines, with special focus on exerkines. These data might provide reference for prevention or treatment of obesity and the related metabolic disease through exercise.

This study aimed to observe the expression of insulin-signaling molecules in different organs of mice with insulin resistance (IR). Firstly, mice were fed a high-fat and high-sugar diet (HF group) to establish an IR model, and the controls (NF group) were fed with a normal diet. Next, the weight, fasting blood glucose (FBG), serum insulin and insulin tolerance were detected. Pathological changes of liver tissues were observed by H&E staining. The expressions of INSR, IRS-1 and IRS-2 in the liver, skeletal muscle and ovary were measured by qRT-PCR and western blotting. As a result, compared with the NF group, the HF group mice had increased weight, FBG, insulin and IR index after 6-week of feeding as well as a worse performance in the insulin tolerance test and H&E staining showed fatty liver-like changes after 12-week of feeding, exhibited lower expression of INSR, IRS-1 and IRS-2 in the liver of mice at 6 and 12 weeks. The expression of INSR and IRS-1 in skeletal muscle tissues exhibited the same trend, while those in ovary organs showed the opposite trend. These results suggested that the insulin signaling alters in the liver, skeletal muscle and ovary organs with the progress of IR.

Background: Mature adipocytes are notoriously difficult to study ex vivo and alternative cell culture systems have therefore been developed. One of the most common models are human adipose progenitor cells (hAPCs). Unfortunately, these display replicative senescence after prolonged culture conditions, which limits their use in mechanistic studies.

Methods: Herein, we knocked in human telomerase reverse transcriptase (TERT) into the AAVS1 locus of CD55⁺ hAPCs derived from abdominal subcutaneous adipose tissue and characterized the cells before and after differentiation into adipocytes.

Results: Immortalized TERT-hAPCs retained proliferative and adipogenic capacities comparable to those of early-passage wild type hAPCs for > 80 passages. In line with this, our integrative transcriptomic and proteomic analyses revealed that TERT-hAPCs displayed robust adipocyte expression profiles in comparison to wild type hAPCs. This was confirmed by functional analyses of lipid turnover where TERT-hAPCs exhibited pronounced responses to insulin and pro-lipolytic stimuli such as isoprenaline, dibutyrul cAMP and tumour necrosis factor alpha. In addition, TERT-hAPCs could be readily cultured in both standard 2D and 3D-cultures and proteomic analyses revealed that the spheroid culture conditions improved adipogenesis.

Conclusion: Through descriptive and functional studies, we demonstrate that immortalization of human CD55⁺ hAPCs is feasible and results in cells with stable proliferative and adipogenic capacities over multiple passages. As these cells are cryopreservable, they provide the additional advantage over primary cells of allowing repeated studies in both 2D and 3D model systems with the same genetic background. (234/250).

Introduction: Mitochondria are essential for generating cellular energy and are significant in the pathogenesis of obesity. Peptide PDBSN has been demonstrated to inhibit the adipogenic differentiation of adipocytes in vitro and improves metabolic homoeostasis in vivo. Therefore, in this study, we further investigated the effects of PDBSN on the morphology, synthesis, and function of adipocyte mitochondria. Methods: Human visceral and subcutaneous primary preadipocytes (HPA-v and HPA-s) were cultured into mature adipocytes. Intracellular triglyceride content was assessed using oil-red O staining and tissue triglyceride determination. Gene and protein levels associated with mitochondrial synthesis were detected using real-time quantitative polymerase chain reaction and western blotting. Mitochondrial membrane potentials and ROS were detected using fluorescent indicators. Morphological changes were observed by electron microscopy. Results: PDBSN significantly increased mitochondrial membrane potential (MMP), while decreasing intracellular triglyceride (TG) and intracellular reactive oxygen species (ROS) levels. On the other hand, the transcription and protein levels of genetic marker genes PGC1-α and MTFA were significantly up-regulated after PDBSN administration. Further studies showed that transcriptional and protein levels of mitochondrial fusion and fission genetic markers MFN1, MFN2, NRF1, and DRP1 increased. Conclusion: PDBSN significantly reduces intracellular TG and ROS levels and increases MMP. The maximum respiratory capacity in adults significantly increases after PDBSN administration, and ROS levels are significantly reduced. This suggests that PDBSN improves mitochondrial function to some extent, which not only provides an essential basis for the pathophysiology of obesity but also provides insights for the development of new drugs to treat obesity and metabolic diseases.

Increasing studies have identified the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in non-alcoholic fatty liver disease (NAFLD) treatment. Hence, we further focused on the potential of adipose-derived MSC (ADSC)-EVs in NAFLD by delivering miR-223-3p. The uptake of isolated ADSC-EVs by hepatocytes was assessed, and the expression of miR-223-3p in ADSC-EVs and hepatocytes was characterized. It was established that miR-223-3p, enriched in ADSC-EVs, could be delivered by ADSC-EVs into hepatocytes. Using co-culture system and gain-of-function approach, we evaluated the effect of ADSC-EVs carrying miR-223-3p on lipid accumulation and liver fibrosis in pyrrolizidine alkaloids (PA)-induced hepatocytes and a high-fat diet-induced NAFLD mouse model. Bioinformatics websites and dual-luciferase reporter gene assay were performed to determine the interactions between miR-223-3p and E2F1, which was further validated by rescue experiments. ADSC-EVs containing miR-223-3p displayed suppressive effects on lipid accumulation and liver fibrosis through E2F1 inhibition, since E2F1 was demonstrated as a target gene of miR-223-3p. The protective role of ADSC-EVs by delivering miR-223-3p was then confirmed in the mouse model. Collectively, this study elucidated that ADSC-EVs delayed the progression NAFLD through the delivery of anti-fibrotic miR-223-3p and subsequent E2F1 suppression, which may suggest miR-223-3p-loaded ADSC-EVs to be a potential therapeutic approach for NAFLD.

High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD. Mice treated with cixutumumab fed standard chow developed mild hyperinsulinemia with no change in WAT. When challenged by HFD mice treated with cixutumumab had reduced weight gain, reduced WAT expansion, and reduced hepatic lipid vacuole formation. In HFD-fed mice, cixutumumab led to reduced levels of genes encoding proteins important in fatty acid metabolism in WAT and liver. Cixutumumab protected against blunting of insulin-stimulated phosphorylation of Akt in liver of HFD fed mice. These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance.

The capacity of adipose stem/progenitor cells (ASCs) to undergo self-renewal and differentiation is crucial for adipose tissue homoeostasis, regeneration and expansion. However, the heterogeneous ASC populations of the adipose lineage constituting adipose tissue are not precisely known. In the present study, we demonstrate that cell surface expression of dipeptidyl peptidase-4 (DPP4)/cluster of differentiation 26 (CD26) subdivides the DLK1^-/CD34⁺/CD45^-/CD31^- ASC pool of human white adipose tissues (WATs) into two large populations. Ex vivo, DPP4⁺ ASCs possess higher self-renewal and proliferation capacity and lesser adipocyte differentiation potential than DDP4^- ASCs. The knock-down of DPP4 in ASC leads to significantly reduced proliferation and self-renewal capacity, while adipogenic differentiation is increased. Ectopic overexpression of DPP4 strongly inhibits adipogenesis. Moreover, in whole mount stainings of human subcutaneous (s)WAT, we detect DPP4 in CD34⁺ ASC located in the vascular stroma surrounding small blood vessels and in mature adipocytes. We conclude that DPP4 is a functional marker for an abundant ASC population in human WAT with high proliferation and self-renewal potential and low adipogenic differentiation capacity.

Interscapular brown adipose tissue (iBAT) of both rabbits and humans exhibits a similar whitening phenomenon under physiological conditions. However, a detailed characterization of iBAT whitening in them is still lacking. Here, we chose rabbits as a model to gain a better understanding of the molecular signature changes during the whitening process of iBAT by transcriptomic analysis of rabbit iBAT at day 1, day 14, 1 month and 4 months after birth. We applied non-invasive MRI imaging to monitor the whitening process and correlated these changes with analysis of morphological, histological and molecular features. Principal component analysis (PCA) of differentially expressed genes delineated three major phases for the whitening process as Brown, Transition and Whitened BAT phases. RNA-sequencing data revealed that whitening of iBAT was an orchestrated process where multiple types of cells and tissues participated in a variety of physiological processes including neovascularization, formation of new nervous networks and immune regulation. Several key metabolic and signalling pathways contributed to whitening of iBAT, and immune cells and immune regulation appeared to play an overarching role.