Intra- and interindividual variation in gene expression in human adipose tissue

Beek, E.A. van; Bakker, A.H.F.; Kruyt, Philip M.; Hofker, Marten H.; Saris, Wim H. M.; Keijer, Jaap

doi:10.1007/s00424-006-0164-4

Cited by 42 publications

(33 citation statements)

References 64 publications

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“…Previous studies reported similar levels of FABP4 mRNA in human VAT and SAT (6,44,45). Our findings that FABP4 protein is higher in both human VAT and mouse intra-abdominal fat suggest that FABP4 may also be regulated posttranscriptionally.…”

Section: Discussionsupporting

confidence: 79%

FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

et al. 2014

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Fatty acid binding protein 4 (FABP4, also known as aP2) is a cytoplasmic fatty acid chaperone expressed primarily in adipocytes and myeloid cells and implicated in the development of insulin resistance and atherosclerosis. Here we demonstrate that FABP4 triggers the ubiquitination and subsequent proteasomal degradation of peroxisome proliferator-activated receptor g (PPARg), a master regulator of adipogenesis and insulin responsiveness. Importantly, FABP4-null mouse preadipocytes as well as macrophages exhibited increased expression of PPARg, and complementation of FABP4 in the macrophages reversed the increase in FABP4 expression. The FABP4-null preadipocytes exhibited a remarkably enhanced adipogenesis compared with wild-type cells, indicating that FABP4 regulates adipogenesis by downregulating PPARg. We found that the FABP4 level was higher and PPARg level was lower in human visceral fat and mouse epididymal fat compared with their subcutaneous fat. Furthermore, FABP4 was higher in the adipose tissues of obese diabetic individuals compared with healthy ones. Suppression of PPARg by FABP4 in visceral fat may explain the reported role of FABP4 in the development of obesity-related morbidities, including insulin resistance, diabetes, and atherosclerosis. Adiposity is closely correlated with important physiological parameters such as blood pressure, systemic insulin sensitivity, dyslipidemia, and serum triglyceride levels (1,2), rendering obesity to an independent risk factor for myocardial infarction, stroke, type 2 diabetes, and certain cancers (3). Among adipose tissues, visceral fat is more closely correlated with obesity-associated pathologies than overall adiposity (4-8).The nuclear receptor peroxisome proliferatoractivated receptor g (PPARg) is a master regulator of adipose cell differentiation, playing a critical role in systemic lipid and glucose metabolism (9). PPARg is activated by natural or synthetic agonists such as the antidiabetic thiazolidinedione (TZD) (10). Activated PPARg is a master regulator of adipogenesis, acting as a transcription factor of genes expressed in mature adipocytes, including fatty acid binding protein (FABP4), CD36, lipoprotein lipase (LPL), and adiponectin, all of which contain peroxisome proliferator response elements (PPREs) (11). PPARg is also expressed in myeloid cells, and its activation promotes an anti-inflammatory phenotype (11). Disruption of PPARg specifically in myeloid cells also predisposes METABOLISMmice to the development of diet-induced obesity, insulin resistance, and glucose intolerance (12), whereas activation of PPARg within macrophages promotes lipid efflux, thereby stabilizing atherosclerotic lesions (13). A major target gene of PPARg is the lipid transporter FABP4, also known as aP2 (14). PPARg induces FABP4 almost exclusively in adipocytes and macrophages. FABP4 acts as a fatty acids chaperone, which couples intracellular lipids to biological targets and signaling pathways (15,16). FABP4 has been implicated in several aspects of the metabolic syndro...

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Section: Discussionsupporting

confidence: 79%

FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

et al. 2014

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“…In our hands, in vivo hASC-mediated calvarial repair does indeed vary between hASC source. Differences in age of the patient, gender, anatomic site of ASC derivation, passage number, and freeze-thaw conditions have all been shown to create disparity in the osteogenic in vitro differentiation of ASCs [35,[57][58][59][60]. We have attempted to counteract this apparent heterogeneity by selecting similar patients for hASC derivation.…”

Section: Discussionmentioning

confidence: 99%

Human Adipose-Derived Stromal Cells Stimulate Autogenous Skeletal Repair via Paracrine Hedgehog Signaling with Calvarial Osteoblasts

Levi

James

Nelson

et al. 2011

Stem Cells and Development

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“…Therefore, our study may serve either as impetus toward the betterment of procedures of cryostorage of hASCs or alternatively toward the avoidance of freezing hASCs in general. Previous observations from our laboratory and others have found that the osteo-and adipogenic differentiation of ASCs does vary based on patient, age, gender, and anatomic site of derivation [51][52][53][54][55]. Thus, to minimize potential heterogeneity, all hASCs were consistently derived from young, female patients from the flank and thigh regions only.…”

Section: Discussionmentioning

confidence: 99%

Deleterious Effects of Freezing on Osteogenic Differentiation of Human Adipose-Derived Stromal Cells In Vitro and In Vivo

James

Lévi

Nelson

et al. 2011

Stem Cells and Development

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Human adipose-derived stromal cells (hASCs) represent a multipotent stromal cell type with a proven capacity to undergo osteogenic differentiation. Many hurdles exist, however, between current knowledge of hASC osteogenesis and their potential future use in skeletal tissue regeneration. The impact of frozen storage on hASC osteogenic differentiation, for example, has not been studied in detail. To examine the effects of frozen storage, hASCs were harvested from lipoaspirate and either maintained in standard culture conditions or frozen for 2 weeks under standard conditions (90% fetal bovine serum, 10% dimethyl sulfoxide). Next, in vitro parameters of cell morphology (surface electron microscopy [EM]), cell viability and growth (trypan blue; bromodeoxyuridine incorporation), osteogenic differentiation (alkaline phosphatase, alizarin red, and quantitative real-time (RT)-polymerase chain reaction), and adipogenic differentiation (Oil red O staining and quantitative RT-polymerase chain reaction) were performed. Finally, in vivo bone formation was assessed using a critical-sized cranial defect in athymic mice, utilizing a hydroxyapatite (HA)-poly(lactic-co-glycolic acid) scaffold for ASC delivery. Healing was assessed by serial microcomputed tomography scans and histology. Freshly derived ASCs differed significantly from freeze-thaw ASCs in all markers examined. Surface EM showed distinct differences in cellular morphology. Proliferation, and osteogenic and adipogenic differentiation were all significantly hampered

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Intra- and interindividual variation in gene expression in human adipose tissue

Abstract: Adipose tissue is a highly plastic tissue with an important endocrine and metabolic function.

Cited by 42 publications

References 64 publications

FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

FABP4 Attenuates PPARγ and Adipogenesis and Is Inversely Correlated With PPARγ in Adipose Tissues

Human Adipose-Derived Stromal Cells Stimulate Autogenous Skeletal Repair via Paracrine Hedgehog Signaling with Calvarial Osteoblasts

Deleterious Effects of Freezing on Osteogenic Differentiation of Human Adipose-Derived Stromal Cells In Vitro and In Vivo

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