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Evidence of impaired adipogenesis in insulin resistance

Published on May 1, 2004in Biochemical and Biophysical Research Communications2.71
· DOI :10.1016/j.bbrc.2004.03.152
Xiaolin Yang4
Estimated H-index: 4
(University of Gothenburg),
Per-Anders Jansson42
Estimated H-index: 42
(University of Gothenburg)
+ 6 AuthorsUlf Smith83
Estimated H-index: 83
(University of Gothenburg)
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Abstract
Abstract To elucidate the roles of adipose tissue and skeletal muscle in the early development of insulin resistance, we characterized gene expression profiles of isolated adipose cells and skeletal muscle of non-diabetic insulin-resistant first-degree relatives of type 2 diabetic patients using oligonucleotide microarrays. About 600 genes and expressed sequence tags, which displayed a gene expression pattern of cell proliferation, were differentially expressed in the adipose cells. The differentially expressed genes in the skeletal muscle were mostly related to the cellular signal transduction and transcriptional regulation. To verify the microarray findings, we studied expression of genes participating in adipogenesis. The expression of Wnt signaling genes, WNT1, FZD1, DVL1, GSK3β, β-catenin, and TCF1, and adipogenic transcription factors, C/EBPα and β and δ, PPARγ, and SREBP-1, was reduced in the adipose tissue. The expression of adipose-specific proteins related to terminal differentiation, such as adiponectin and aP2, was reduced both in the adipose tissue and in the adipose cells isolated from portions of the biopsies. The adipose cells were enlarged in the insulin-resistant relatives and the cell size inversely correlated with the expression of the Wnt signaling genes, adiponectin, and aP2. Our findings suggest that insulin resistance is associated with an impaired adipogenesis.
  • References (30)
  • Citations (143)
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References30
Newest
Published on Aug 1, 2003in The FASEB Journal5.39
Per-Anders Jansson42
Estimated H-index: 42
,
Fredrik Pellmé4
Estimated H-index: 4
+ 12 AuthorsTohru Funahashi104
Estimated H-index: 104
(Osaka University)
The epidemic increase in type 2 diabetes can be prevented only if markers of risk can be identified and used for early intervention. We examined the clinical phenotype of individuals characterized by normal or low IRS-1 protein expression in fat cells as well as the potential molecular mechanisms related to the adipose tissue. Twenty-five non-obese individuals with low or normal IRS-1 expression in subcutaneous abdominal fat cells were extensively characterized and the results compared with 71 c...
Published on May 1, 2003in Diabetes7.20
Fredrik Pellmé4
Estimated H-index: 4
,
Ulf Smith83
Estimated H-index: 83
+ 5 AuthorsPer-Anders Jansson42
Estimated H-index: 42
Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity ( S i ) was studied with the minimal model, and measurements...
Published on Feb 1, 2003in Biochemical and Biophysical Research Communications2.71
A. Hammarstedt7
Estimated H-index: 7
(Sahlgrenska University Hospital),
Per-Anders Jansson42
Estimated H-index: 42
(Sahlgrenska University Hospital)
+ 2 AuthorsUlf Smith83
Estimated H-index: 83
(Sahlgrenska University Hospital)
Abstract Peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1 (PGC-1) regulates glucose metabolism and energy expenditure and, thus, potentially insulin sensitivity. We examined the expression of PGC-1, PPARγ, insulin receptor substrate-1 (IRS-1), glucose transporter isoform-4 (GLUT-4), and mitochondrial uncoupling protein-1 (UCP-1) in adipose tissue and skeletal muscle from non-obese, non-diabetic insulin-resistant, and insulin-sensitive individuals. PGC-1, both mRNA and protein,...
Published on Nov 1, 2002in Diabetologia7.11
Xiaolin Yang8
Estimated H-index: 8
(Sahlgrenska University Hospital),
R. E. Pratley4
Estimated H-index: 4
(Novartis)
+ 2 AuthorsPaskasari A. Permana7
Estimated H-index: 7
(NIH: National Institutes of Health)
Aims/hypothesis. We carried out global transcript profiling to identify differentially expressed skeletal muscle genes in insulin resistance, a major risk factor for Type II (non-insulin-dependent) diabetes mellitus. This approach also complemented the ongoing genomic linkage analyses to identify genes linked to insulin resistance and diabetes in Pima Indians. Methods. We compared gene expression profiles of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally ob...
Published on Jul 19, 2002in Journal of Biological Chemistry
Naoto Kubota53
Estimated H-index: 53
,
Yasuo Terauchi57
Estimated H-index: 57
+ 13 AuthorsHidemi Satoh4
Estimated H-index: 4
Abstract The adipocyte-derived hormone adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity, and it has been reported to exhibit putative antiatherogenic properties in vitro. In this study we generated adiponectin-deficient mice to directly investigate whether adiponectin has a physiological protective role against diabetes and atherosclerosis in vivo. Heterozygous adiponectin-deficient (adipo +/−) mice showed mild insulin resistan...
Published on Jul 1, 2002in International Journal of Obesity4.51
Ulf Smith83
Estimated H-index: 83
(University of Gothenburg)
Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance—is insulin resistance initiated in the adipose tissue?
Published on Apr 1, 2002in Nature Medicine30.64
Masataka Sata59
Estimated H-index: 59
(UTokyo: University of Tokyo),
Akio Saiura29
Estimated H-index: 29
(UTokyo: University of Tokyo)
+ 7 AuthorsRyouzou Nagai111
Estimated H-index: 111
(UTokyo: University of Tokyo)
Excessive accumulation of smooth-muscle cells (SMCs) has a key role in the pathogenesis of vascular diseases. It has been assumed that SMCs derived from the outer medial layer migrate, proliferate and synthesize extracellular matrix components on the luminal side of the vessel. Although much effort has been devoted to targeting migration and proliferation of medial SMCs, there is no effective therapy that prevents occlusive vascular remodeling. We show here that in models of post-angioplasty res...
Published on Mar 1, 2002in Nature Reviews Molecular Cell Biology43.35
David Tosh32
Estimated H-index: 32
(University of Bath),
Jonathan M.W. Slack58
Estimated H-index: 58
(University of Bath)
Until recently, it was thought that once a cell had acquired a stable differentiated state, it could not change its phenotype. We now know this is not the case, and over the past few years a plethora of well-documented examples have been presented whereby already differentiated cells or tissue-specific stem cells have been shown to alter their phenotype to express functional characteristics of a different tissue. In this chapter, we examine evidence for these examples, comment on the underlying ...
Published on Jan 1, 2002in Progress in Neurobiology10.66
Lukas Sommer46
Estimated H-index: 46
(EPFL: École Polytechnique Fédérale de Lausanne),
Mahendra S. Rao71
Estimated H-index: 71
(NIH: National Institutes of Health)
Abstract Normal CNS development involves the sequential differentiation of multipotent stem cells. Alteration of the numbers of stem cells, their self-renewal ability, or their proliferative capacity will have major effects on the appropriate development of the nervous system. In this review, we discuss different mechanisms that regulate neural stem cell differentiation. Proliferation signals and cell cycle regulators may regulate cell kinetics or total number of cell divisions. Loss of trophic ...
Published on May 18, 2001in Journal of Biological Chemistry
Soazig Le Lay1
Estimated H-index: 1
(University of Paris),
S Krief12
Estimated H-index: 12
(University of Paris)
+ 5 AuthorsIsabelle Dugail33
Estimated H-index: 33
(University of Paris)
Abstract Enlarged fat cells exhibit modified metabolic capacities, which could be involved in the metabolic complications of obesity at the whole body level. We show here that sterol regulatory element-binding protein 2 (SREBP-2) and its target genes are induced in the adipose tissue of several models of rodent obesity, suggesting cholesterol imbalance in enlarged adipocytes. Within a particular fat pad, larger adipocytes have reduced membrane cholesterol concentrations compared with smaller fat...
Cited By143
Newest
Published on Sep 16, 2019in Journal of Clinical Investigation12.28
Gordon I. Smith3
Estimated H-index: 3
,
Bettina Mittendorfer47
Estimated H-index: 47
,
Samuel Klein89
Estimated H-index: 89
Published on Feb 18, 2019in International Journal of Obesity4.51
Pulavendran Sivasami1
Estimated H-index: 1
(OSU: Oklahoma State University–Stillwater),
Nabin Poudel1
Estimated H-index: 1
(OSU: Oklahoma State University–Stillwater)
+ 5 AuthorsMyron E. Hinsdale10
Estimated H-index: 10
(University of Oklahoma Health Sciences Center)
The cellular and extracellular matrix (ECM) interactions that regulate adipose tissue homeostasis are incompletely understood. Proteoglycans (PGs) and their sulfated glycosaminoglycans (GAGs) provide spatial and temporal signals for ECM organization and interactions with resident cells by impacting growth factor and cytokine activity. Therefore, PGs and their GAGs could be significant to adipose tissue homeostasis. The purpose of this study was to determine the role of ECM sulfated GAGs in adipo...
Published on Jul 1, 2019in Domestic Animal Endocrinology2.30
Ikuyo Nakajima16
Estimated H-index: 16
(National Agriculture and Food Research Organization),
M. Kojima (National Agriculture and Food Research Organization)+ 3 AuthorsKoichi Chikuni24
Estimated H-index: 24
(National Agriculture and Food Research Organization)
Abstract Here we characterized gene expressions in subcutaneous adipose tissue and blood metabolites of pigs with genetically low backfat (Landrace) and high backfat (Meishan). As pigs aged from 1 wk-to 3-mo old, mRNA levels of adipose-specific genes increased, although their gene expressions coding for major enzymes involved in lipid metabolism (lipoprotein lipase, fatty acid synthase, and hormone-sensitive lipase) did not differ between lean and fat pigs. Instead, there were significant effect...
Published on Mar 1, 2019in Journal of Cellular Physiology4.52
Hanél Sadie-Van Gijsen3
Estimated H-index: 3
(Stellenbosch University)
Abstract Globally, the obesity pandemic is profoundly affecting quality of life and economic productivity, but efforts to address this, especially on a pharmacological level, have generally proven unsuccessful to date, serving as a stark demonstration that our understanding of adipocyte biology and pathophysiology is incomplete. To deliver better insight into adipocyte function and obesity, we need improved adipocyte models with a high degree of fidelity in representing the in vivo state and wit...
Published on Mar 1, 2019in Biochemical and Biophysical Research Communications2.71
Won Jun Kim12
Estimated H-index: 12
(UOU: University of Ulsan),
Woojung Lee (Ministry of Food and Drug Safety)+ 3 AuthorsSu-Nam Kim18
Estimated H-index: 18
(KIST: Korea Institute of Science and Technology)
Abstract Previous reports have shown that PPARβ/δ agonists ameliorate insulin resistance associated with type 2 diabetes mellitus (T2DM). To determine the role of PPARβ/δ in tumor necrosis factor α (TNFα)-mediated insulin resistance, we investigated expression levels of adiponectin and insulin receptor (IR) in response to treatment with the PPARβ/δ agonist GW501516 with or without TNFα, a proinflammatory cytokine, in differentiated 3T3-L1 adipocytes. GW501516 induced adipocyte differentiation an...
Published on Oct 1, 2018in Physiological Reviews24.25
Ann Hammarstedt26
Estimated H-index: 26
(University of Gothenburg),
Silvia Gogg9
Estimated H-index: 9
(University of Gothenburg)
+ 2 AuthorsUlf Smith83
Estimated H-index: 83
(University of Gothenburg)
The subcutaneous adipose tissue (SAT) is the largest and best storage site for excess lipids. However, it has a limited ability to expand by recruiting and/or differentiating available precursor ce...
Published on Sep 13, 2018in PLOS ONE2.78
Sarah L. O’Beirne5
Estimated H-index: 5
(Cornell University),
Jacqueline Salit19
Estimated H-index: 19
(Cornell University)
+ 18 AuthorsMahmoud Zirie15
Estimated H-index: 15
(Hamad Medical Corporation)
Karin G. Stenkula11
Estimated H-index: 11
,
Charlotte Erlanson-Albertsson34
Estimated H-index: 34
(Lund University)
Adipose tissue is necessary to harbour energy. To handle excess energy, adipose tissue expands by increasing adipocyte size (hypertrophy) and number (hyperplasia). Here, we have summarized the different experimental techniques used to study adipocyte cell size and describe adipocyte size in relation to insulin resistance, type 2 diabetes and diet interventions. Hypertrophic adipocytes have an impaired cellular function and inherent mechanisms restrict their expansion to protect against cell brea...
Published on Jun 20, 2018in PLOS ONE2.78
James Reneau , Matthew I. Goldblatt14
Estimated H-index: 14
+ 11 AuthorsBrittaney Obi1
Estimated H-index: 1
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