Glucose transport is equally sensitive to insulin stimulation, but basal and insulin-stimulated transport is higher, in human omental compared with subcutaneous adipocytes

Westergren, Hanna; Danielsson, Anna; Nyström, Fredrik; Strålfors, Peter

doi:10.1016/j.metabol.2005.01.021

Cited by 14 publications

(14 citation statements)

References 17 publications

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“…Consequently, the low PPARG activity in the intra-abdominal fat cells is in line with the high levels of GLUT4 in intraabdominal as compared with subcutaneous adipocytes that were reported by us earlier [23].…”

Section: Discussionsupporting

confidence: 87%

Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes

et al. 2006

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Aims/hypothesis The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse. Materials and methods We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light.Results We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n=23). The activity was also 6.2-fold higher in subcutaneous than in intraabdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 μmol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells. Conclusions/interpretation We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

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Section: Discussionsupporting

confidence: 87%

Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes

et al. 2006

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“…For both insulin and IGF-I the activation was accompanied by biological effects in the form of glucose accumulation and DNA synthesis. The effect of IGF-I and insulin on glucose was moderate in PA compared to what has been reported for mature adipocytes (33). This is probably due to glucose transport by GLUT1 while insulin sensitive GLUT4 transporters are poorly developed as suggested by the low gene expression.…”

Section: Dna Synthesismentioning

confidence: 65%

Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes

Bäck

Arnqvist

2009

Growth Hormone & IGF Research

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Mature adipocytes originate from fibroblast-like precursor cells, preadipocytes, which differentiate to obtain the characteristics of adipocytes. Our aim was to investigate how differentiation of human preadipocytes affects the distribution of insulin receptors (IR) and IGF-I receptors (IGF-IR) and other cell characteristics. Preadipocytes were differentiated using indomethacine, dexamethasone, isobutyl-methylxantine (IBMX) and high concentration of insulin. Gene expression was quantified by real-time RT-PCR in preadipocytes (PA), differentiated preadipocytes (dPA) and mature adipocytes (mAD). The amount of expressed receptor protein was analyzed using receptor specific ELISAs and Western blot. We also studied DNA synthesis with radiolabeled thymidine incorporation and glucose accumulation with radiolabeled glucose. Differentiation of PA increased gene expression of IR but not IGF-IR. GLUT4, growth hormone receptor (GHR) and adiponectin appeared or increased. In PA and dPA only IR-A was expressed whereas also IR-B was detected in mAD. By Western blot and ELISA, IR and IGF-IR were detected in PA, dPA and mAD. During differentiation the ratio of IR to IGF-IR increased severalfold. In PA both the IR and the IGF-IR was phosphorylated by their own ligand at 1 nM and in dPA the activation of both receptors was stimulated by IGF-I, but not insulin, at 1 nM. Accumulation of glucose in PA was increased by insulin at 10 nM and by IGF-I at 1 nM and 10 nM. DNA synthesis was increased by insulin and IGF-I at 10 nM.In conclusion, both IR and IGF-IR are present in human preadipocytes and adipocytes.Differentiation is characterized by an increased IR/IGF-IR ratio.

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“…Several studies have already demonstrated differences between VAT and SAT regarding secretion of inflammatory mediators, gene expression, and cell morphology. Yet glucose utilization between these two adipose compartments remains incompletely understood (7–10). A recent study shows that AT glucose uptake determined by fluorodeoxyglucose positron emission tomography (FdG-PET) may complement volumetric measurements of fat for the purpose of risk estimation (11).…”

Section: Introductionmentioning

confidence: 99%

Increased Glucose Uptake in Visceral Versus Subcutaneous Adipose Tissue Revealed by PET Imaging

Christen

Sheikine

Rocha

et al. 2010

JACC: Cardiovascular Imaging

104

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Objective The current study tested the hypothesis that glucose utilization differs between VAT and SAT and investigated potential mechanisms for such a finding. Background Visceral adipose tissue (VAT) burden correlates better with cardiovascular risk than does subcutaneous adipose tissue (SAT) burden. Beyond volumetric measurement, glucose uptake in adipose tissue (AT) might reflect metabolic activity and provide pathophysiologic insight and aid risk stratification. Methods We retrospectively studied tissue-specific glucose uptake in vivo in clinically obtained whole-body fluorodeoxyglucose positron emission tomography (FdG-PET) scans. We also assessed glucose uptake in vitro, using stromal vascular cells isolated from SAT and VAT of diet-induced obese C57BL/6 mice. Quantitative PCR evaluated the expression of multiple genes involved in cellular glucose metabolism, including glucose transporters (GLUT 1, 3 and 4) and hexokinases (HK-1 and 2) in SAT and VAT of obese C57BL/6 mice. Results We analyzed whole-body FdG-PET scans from 31 obese and 26 lean patients. VAT exhibited higher FdG uptake compared to SAT (p<0.0001) independent of age, gender, body-mass index, comorbidities, and medications. To investigate mechanisms underlying this observation, we studied glucose uptake in the stromal vascular cell fraction of AT, rich in inflammatory cells. Stromal vascular cells from VAT of diet-induced obese C57BL/6 mice exhibited higher glucose uptake than those from SAT (p=0.01). Evaluation of expression of glucose transporters (GLUT 1, 3 and 4) and hexokinases (HK-1 and 2), revealed increased expression of HK-1 in VAT- compared to SAT-derived stromal vascular cells, and also in visceral versus subcutaneous unfractionated AT. Conclusions In humans in vivo, VAT has increased glucose uptake compared with SAT, as determined non-invasively with FdG PET imaging. Differential stromal metabolic activity may be one mechanism underlying differences in metabolic activity of visceral and subcutaneous AT.

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Glucose transport is equally sensitive to insulin stimulation, but basal and insulin-stimulated transport is higher, in human omental compared with subcutaneous adipocytes

Cited by 14 publications

References 17 publications

Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes

Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes

Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes

Increased Glucose Uptake in Visceral Versus Subcutaneous Adipose Tissue Revealed by PET Imaging

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