Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity.
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ABSTRACT:
SUBMITTER: Colon-Mesa I
PROVIDER: S-EPMC8584112 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Biological aging alters the metabolism and volume of adipose tissue depots. Recent evidence suggests that circadian mechanisms play a role in promoting adipogenesis, obesity, and lipodystrophy. The current study compared cohorts of younger (5-9 months) and older (24-28 months) C57BL/6 mice as a function of biological age and circadian time. Advanced age significantly reduced the weight of the brown, epididymal, inguinal, and retroperitoneal adipose depots but not total body weight. The older mice reduced their physical activity by >50% and delayed their activity initiation after light offset. The expressed transcriptome in brown and white adipose depots and liver of both cohorts displayed evidence of circadian rhythmicity; however, the oscillating mRNAs differed significantly between age groups and across tissues. The amplitude of Cry1, a component of the negative arm of the circadian apparatus, and downstream regulators such as Rev-erb? were elevated in the older relative to the younger cohorts as a function of circadian time. Overall, transcript levels differed significantly for 557 (inguinal adipose), 1,016 (liver), and 1,021 (brown adipose) expressed sequences between the cohorts as a function of age. These included transcripts encoding proteins within the canonical and non-canonical Wnt pathways. Since the Wnt pathway regulates adipose stem cell differentiation and shares a critical enzyme, glycogen synthase kinase 3?, with the circadian mechanism, the intersection between these two fundamental regulatory mechanisms merits further investigation with respect to biological aging of adipose tissues.
| S-EPMC3636385 | biostudies-literature
Project description:BackgroundThe composition and function of the adipose tissue covering the heart are poorly known. In this study, we have investigated the epicardial adipose tissue (EAT) covering the cardiac ventricular muscle and the EAT covering the left anterior descending artery (LAD) on the human heart, to identify their resident stem cell functional activity.MethodsEAT covering the cardiac ventricular muscle was isolated from the apex (avoiding areas irrigated by major vessels) of the heart (ventricular myocardium adipose tissue (VMAT)) and from the area covering the epicardial arterial sulcus of the LAD (PVAT) in human hearts excised during heart transplant surgery. Adipose stem cells (ASCs) from both adipose tissue depots were immediately isolated and phenotypically characterized by flow cytometry. The different behavior of these ASCs and their released secretome microvesicles (MVs) were investigated by molecular and cellular analysis.ResultsASCs from both VMAT (mASCs) and the PVAT (pASCs) were characterized by the expression of CD105, CD44, CD29, CD90, and CD73. The angiogenic-related genes VEGFA, COL18A1, and TF, as well as the miRNA126-3p and miRNA145-5p, were analyzed in both ASC types. Both ASCs were functionally able to form tube-like structures in three-dimensional basement membrane substrates. Interestingly, pASCs showed a higher level of expression of VEGFA and reduced level of COL18A1 than mASCs. Furthermore, MVs released by mASCs significantly induced human microvascular endothelial cell migration.ConclusionOur study indicates for the first time that the resident ASCs in human epicardial adipose tissue display a depot-specific angiogenic function. Additionally, we have demonstrated that resident stem cells are able to regulate microvascular endothelial cell function by the release of MVs.
| S-EPMC6884762 | biostudies-literature
Project description:BackgroundVisceral adipose tissue (VAT) and fatty liver differ in their associations with cardiovascular risk compared with subcutaneous adipose tissue (SAT). Several biomarkers have been linked to metabolic derangements and may contribute to the pathogenicity of fat depots. We examined the association between fat depots on multidetector computed tomography and metabolic regulatory biomarkers.Methods and resultsParticipants from the Framingham Heart Study (n=1583, 47% women) underwent assessment of SAT, VAT, and liver attenuation. We measured circulating biomarkers secreted by adipose tissue or liver (adiponectin, leptin, leptin receptor, fatty acid binding protein 4, fetuin-A, and retinol binding protein 4). Using multivariable linear regression models, we examined relations of fat depots with biomarkers. Higher levels of fat depots were positively associated with leptin and fatty acid binding protein 4 but negatively associated with adiponectin (all P<0.001). Associations with leptin receptor, fetuin-A, and retinol binding protein 4 varied according to fat depot type or sex. When comparing the associations of SAT and VAT with biomarkers, VAT was the stronger correlate of adiponectin (?=-0.28 [women]; ?=-0.30 [men]; both P<0.001), whereas SAT was the stronger correlate of leptin (?=0.62 [women]; ?=0.49 [men]; both P<0.001; P<0.001 for comparing VAT versus SAT). Although fetuin-A and retinol binding protein 4 are secreted by the liver in addition to adipose tissue, associations of liver attenuation with these biomarkers was not stronger than that of SAT or VAT.ConclusionsSAT, VAT, and liver attenuation are associated with metabolic regulatory biomarkers with differences in the associations by fat depot type and sex. These findings support the possibility of biological differences between fat depots.
| S-EPMC4889173 | biostudies-literature
Project description:Depending on its anatomical placement, perivascular adipose tissue (PVAT) has been found to possess features more (e.g., aortic thoracic) or less (e.g., aortic abdominal) similar to brown/beige adipose tissue in mice, whereas PVAT surrounding the mesenteric arteries and the caudal part of abdominal aorta is similar to white fat. PVAT is thought to influence vascular function through the effects of adipose-secreted molecules on vessels. Brown adipose tissue was recently shown to play differential secretory role via secretion of the so-called batokines but the involvement of differential batokine production in PVAT brown/beige plasticity was unclear. The current study characterizes for the first time the expression of batokines at aortic thoracic PVAT (tPVAT) and aortic abdominal PVAT (aPVAT) in comparison with typical brown and white adipose depots, in basal and thermogenically activated conditions. We found that both PVAT depots increased their expression of genes encoding the batokines bone morphogenetic protein-8b (BMP8B), fibroblast growth factor-21 (FGF21), and kininogen-2 (KNG2) in response to cold, indicating that, under cold-induced thermogenic activation, both thoracic aorta and abdominal aorta would experience intense local exposure to these PVAT-secreted batokines. In contrast, the gene expression levels of growth/differentiation factor-15 and vascular endothelial growth factor-A were induced only in tPVAT. Under short-term high-fat diet-induced thermogenic activation, the thoracic aorta would be specifically exposed to a local increase in PVAT-originating BMP8B, FGF21, and KNG2. Our data support the notion that acquisition of a brown/beige phenotype in PVAT is associated with upregulation of batokines, mainly BMP8B, FGF21, and KNG2, that can differentially target the vascular system.
| S-EPMC8373243 | biostudies-literature
Project description:Obesity and aging represent major health burdens to the global adult population. Both conditions promote the development of associated metabolic diseases such as insulin resistance. The visceral adipose tissue (VAT) is a site that becomes dysfunctional during obesity and aging, and plays a significant role during their pathophysiology. The changes in obese and aging VAT are now recognized to be partly driven by a chronic local inflammatory state, characterized by immune cells that typically adopt an inflammatory phenotype during metabolic disease. Here, we summarize the current knowledge on the immune cell landscape of the VAT during lean, obese, and aged conditions, highlighting their similarities and differences. We also briefly discuss possible linked mechanisms that fuel obesity- and age-associated VAT dysfunction.
| S-EPMC7243349 | biostudies-literature
Project description:Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is rapidly increasing as the number of older people increases worldwide, making this condition a medical and social problem. Some patients with sarcopenia exhibit accumulation of peri-muscular adipose tissue (PMAT) as ectopic fat deposition surrounding atrophied muscle. However, an association of PMAT with muscle atrophy has not been demonstrated. Here, we show that PMAT is associated with muscle atrophy in aged mice and that atrophy severity increases in parallel with cumulative doses of PMAT. We observed severe muscle atrophy in two different obese model mice harboring significant PMAT relative to respective control non-obese mice. We also report that denervation-induced muscle atrophy was accelerated in non-obese young mice transplanted around skeletal muscle with obese adipose tissue relative to controls transplanted with non-obese adipose tissue. Notably, transplantation of obese adipose tissue into peri-muscular regions increased nuclear translocation of FoxO transcription factors and upregulated expression FoxO targets associated with proteolysis (Atrogin1 and MuRF1) and cellular senescence (p19 and p21) in muscle. Conversely, in obese mice, PMAT removal attenuated denervation-induced muscle atrophy and suppressed upregulation of genes related to proteolysis and cellular senescence in muscle. We conclude that PMAT accumulation accelerates age- and obesity-induced muscle atrophy by increasing proteolysis and cellular senescence in muscle.
| S-EPMC6707561 | biostudies-literature
Project description:White adipose tissue is deposited mainly as subcutaneous adipose tissue (SAT), often associated with metabolic protection, and abdominal/visceral adipose tissue, which contributes to metabolic disease. To investigate the molecular underpinnings of these differences, we conducted comprehensive proteomics profiling of whole tissue and isolated adipocytes from these two depots across two diets from C57Bl/6J mice. The adipocyte proteomes from lean mice were highly conserved between depots, with the major depot-specific differences encoded by just 3% of the proteome. Adipocytes from SAT (SAdi) were enriched in pathways related to mitochondrial complex I and beiging, whereas visceral adipocytes (VAdi) were enriched in structural proteins and positive regulators of mTOR presumably to promote nutrient storage and cellular expansion. This indicates that SAdi are geared toward higher catabolic activity, while VAdi are more suited for lipid storage. By comparing adipocytes from mice fed chow or Western diet (WD), we define a core adaptive proteomics signature consisting of increased extracellular matrix proteins and decreased fatty acid metabolism and mitochondrial Coenzyme Q biosynthesis. Relative to SAdi, VAdi displayed greater changes with WD including a pronounced decrease in mitochondrial proteins concomitant with upregulation of apoptotic signaling and decreased mitophagy, indicating pervasive mitochondrial stress. Furthermore, WD caused a reduction in lipid handling and glucose uptake pathways particularly in VAdi, consistent with adipocyte de-differentiation. By overlaying the proteomics changes with diet in whole adipose tissue and isolated adipocytes, we uncovered concordance between adipocytes and tissue only in the visceral adipose tissue, indicating a unique tissue-specific adaptation to sustained WD in SAT. Finally, an in-depth comparison of isolated adipocytes and 3T3-L1 proteomes revealed a high degree of overlap, supporting the utility of the 3T3-L1 adipocyte model. These deep proteomes provide an invaluable resource highlighting differences between white adipose depots that may fine-tune their unique functions and adaptation to an obesogenic environment.
| S-EPMC10014311 | biostudies-literature
Project description:Here we report that lean mice infected with the intracellular parasite Neospora caninum show a fast but sustained increase in the frequency of IFN-γ-producing cells noticeable in distinct adipose tissue depots. Moreover, IFN-γ-mediated immune memory could be evoked in vitro in parasite antigen-stimulated adipose tissue stromal vascular fraction cells collected from mice infected one year before. Innate or innate-like cells such as NK, NK T and TCRγδ(+) cells, but also CD4(+) and CD8(+) TCRβ(+) lymphocytes contributed to the IFN-γ production observed since day one of infection. This early cytokine production was largely abrogated in IL-12/IL23 p40-deficient mice. Moreover, production of IFN-γ by stromal vascular fraction cells isolated from these mice was markedly lower than that of wild-type counterparts upon stimulation with parasite antigen. In wild-type mice the increased IFN-γ production was concomitant with up-regulated expression of genes encoding interferon-inducible GTPases and nitric oxide synthase, which are important effector molecules in controlling intracellular parasite growth. This increased gene expression was markedly impaired in the p40-deficient mice. Overall, these results show that NK cells but also diverse T cell populations mediate a prompt and widespread production of IFN-γ in the adipose tissue of N. caninum infected mice.
| S-EPMC4802212 | biostudies-literature
Project description:Adipose tissue (AT) is a multi-depot organ in mammals. AT from various depots differs in composition and function. Revealing the composition feature of AT depots will provide valuable information for further research on the development and fat deposition patterns in buffalo. This study explored the cellular morphology and gene expression profiles of brown and beige markers in seven AT depots of fattened buffalo: three subcutaneous depots (back, sternum, and inguinal) and four visceral depots (perirenal, mesenteric, pericardial, and omental). Histological results showed unilocular adipocytes in all seven AT depots. Uncoupling protein 1 (UCP1) mRNA, a brown and beige adipocyte gene, was detected in all depots with the highest level in VAT depots, and a limited number of UCP1-positive unilocular adipocytes were observed in the three VAT depots. The mRNAs of PPARG coactivator 1 alpha (PGC1 ? ) and transmembrane protein 26 (TMEM26), brown or beige adipocyte markers, were identified in all seven depots and were mainly expressed in VAT depots. However, the mRNA of zinc finger protein of the cerebellum 1 (ZIC1), a brown adipocyte-specific marker, was almost undetectable. Our results demonstrated that all seven AT depots are white adipose tissue (WAT), with potential function of non-shivering thermogenesis in fattened buffalo. Beige adipocytes are more active in VAT depots than in WAT depots. These results improve our knowledge on the feature of different adipose tissue depots in buffalo, which will be useful for the research of fat deposition.
| S-EPMC7059603 | biostudies-literature
Project description:The widespread prevalence of obesity has lead to extensive research on white adipose tissue (WAT), which frequently uses the C57BL/6J mouse strain as a model. In many studies, results obtained in one WAT depot are often extrapolated to all WAT. However, functional differences among WAT depots are now becoming apparent. Thus, to identify the molecular mechanisms responsible for WAT depot-specific differences under "normal" conditions, four C57BL/6J mouse WAT depots (inguinal, mesenteric, epididymal, and retroperitoneal) were analyzed. Depot proteomic profiles, along with weights, protein contents, adipocyte sizes and oxidative stress were determined. Mesenteric WAT had almost twice the protein content of the other depots analyzed. Mean adipocyte size was highest in epididymal and lowest in mesenteric and inguinal depots. The proteome of inguinal WAT displayed low levels of enzymes involved in ATP generation, glucose and lipid metabolism, and antioxidant proteins. Higher levels of these proteins were observed in mesenteric and epididymal WAT, with variable levels in the retroperitoneal depot. Some of these proteins showed depot-specific correlations with plasma levels of insulin, leptin, and adiponectin. In agreement with the proteomic data, levels of the antioxidant protein heat shock protein ?1 (HSP?1) also were lower in inguinal WAT when analyzed by western blotting and immunohistochemistry. Also, lipid peroxidation products showed similar trends. Our results are consistent with lower triglyceride turnover and lower oxidative stress in inguinal than mesenteric and epididymal WAT. The observed WAT depot-specific differences provide clues as to the mechanisms leading to these depots' respective diverse functions.
| S-EPMC3666351 | biostudies-literature