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- Gabrielsson, Britt, 1957, et al.
(författare)
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Molecular characterization of a local sulfonylurea system in human adipose tissue.
- 2004
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Ingår i: Molecular and cellular biochemistry. - 0300-8177 .- 1573-4919. ; 258:1-2, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- ATP-sensitive potassium (KATP) channels are present in many cell types and link cellular metabolism to the membrane potential. These channels are heterooctamers composed of two subunits. The sulfonylurea receptor (SUR) subunits are targets for drugs that are inhibitors or openers of the KATP channels, while the inwardly rectifying K+ (Kir) subunits form the ion channel. Two different SUR genes (SUR1 and SUR2) and two different Kir6.x genes (Kir6.1 and Kir6.2) have been identified. In addition, isoforms of SUR2, SUR2A and SUR2B, have been described. We have previously performed expression profiling on pooled human adipose tissue and found high expression of SUR2. Others have reported expression of SUR1 in human adipocytes. The aim of this study was to characterize the expression of the sulfonylurea receptor complex components in human adipose tissue. RT-PCR analysis, verified by restriction enzyme digestions and DNA sequencing, showed that SUR2B, Kir6.1 and alpha-endosulfine, but not SUR1, SUR2A or Kir6.2, are expressed in human adipose tissue. Real-time RT-PCR showed that SUR2B was expressed at higher levels in subcutaneous compared with omental adipose tissue in paired biopsies obtained from seven obese men (p < 0.05). Analysis of tissue distribution showed that SUR2B expression in adipose tissue was lower than that in muscle, similar to that in heart and liver, while the expression in pancreas was lower. The effect of caloric restriction was tested in obese men (n = 10) treated with very low calorie diet for 16 weeks, followed by a gradual reintroduction of ordinary food for 2 weeks. Biopsies were taken at week 0, 8 and 18. There was no consistent effect of weight reduction on SUR2B or Kir6.1 expression. We conclude that the necessary components for a local sulfonylurea system are expressed in human adipose tissue and that the sulfonylurea receptor complex in this tissue is composed of SUR2B and Kir6.1. The expression of SUR2B was higher in subcutaneous compared with omental adipose tissue and was not affected by weight loss.
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- Chen, Yun, 1966, et al.
(författare)
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Neonatal losartan treatment suppresses renal expression of molecules involved in cell-cell and cell-matrix interactions
- 2004
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Ingår i: Journal of the American Society of Nephrology. - : Lippincott Williams & Wilkins. - 1046-6673 .- 1533-3450. ; 15:5, s. 1232-43
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Tidskriftsartikel (refereegranskat)abstract
- Lack of neonatal angiotensin II type 1 receptor (AT(1)) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT(1) receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, approximately 30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, alpha-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin alpha6 and caused relocalization of integrins alpha6 and alpha3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT(1) receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and alpha-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.
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- Gabrielsson, Britt, 1957, et al.
(författare)
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Depot-specific expression of fibroblast growth factors in human adipose tissue.
- 2002
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Ingår i: Obesity research. - : Wiley. - 1071-7323 .- 1550-8528. ; 10:7, s. 608-16
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the expression of several fibroblast growth factors (FGFs) and FGF-receptors (FGFRs) in human adipose tissue and adipose-tissue cell fractions obtained from both subcutaneous (sc) and omental (om) depots.
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- Gabrielsson, Britt, 1957, et al.
(författare)
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High expression of complement components in omental adipose tissue in obese men.
- 2003
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Ingår i: Obesity research. - : Wiley. - 1071-7323 .- 1550-8528. ; 11:6, s. 699-708
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Accumulation of visceral fat is recognized as a predictor of obesity-related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. RESEARCH METHODS AND PROCEDURES: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real-time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. RESULTS: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue ( approximately 2-, 4-, 17-, 10-, and 7-fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). DISCUSSION: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra-abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.
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- Gabrielsson, Britt, 1957, et al.
(författare)
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Partial genome scale analysis of gene expression in human adipose tissue using DNA array
- 2000
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 8:5, s. 374-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Large scale analysis of gene expression in adipose tissue provides a basis for the identification of novel candidate genes involved in the pathophysiology of obesity. Our goal was to explore gene expression in human adipose tissue at a partial genome scale using DNA array. RESEARCH METHODS AND PROCEDURES: Labeled cDNA, derived from human adipose tissue poly(A+) RNA, was hybridized to a DNA array containing over 18,000 human expressed sequence-tagged (EST) clones. The results were analyzed by database searches. RESULTS: Homology searches of the 300 EST clones with highest hybridization signals revealed that 145 contained DNA sequences identical to known genes and 79 could be linked to UniGene clusters. Of the 145 identified genes, 136 were nonredundant and subsequently characterized with respect to function and chromosomal localization by searching MEDLINE, UniGene, GeneMap, OMIM, SWISS-PROT, the Genome Database, and the Location Data Base. The identified genes were grouped according to their putative functions; cell/organism defense (9.6%), cell division (5.1%), cell signaling/communication (19.8%), cell structure/motility (12.5%), gene/ protein expression (16.9%), metabolism (16.2%), and unclassified (19.8%). Less than 50% of these genes have previously been reported to be expressed in adipose tissue. The chromosomal localization of 268 genes strongly expressed in adipose tissue showed that their relative abundance was significantly increased on chromosomes 11, 19, and 22 compared to the expected distribution of the same number of random genes. DISCUSSION: Our study resulted in the identification of numerous genes previously not reported to be expressed in adipose tissue. These results suggest that DNA array is a powerful tool in the search for novel regulatory pathways within adipose tissue on a scale that is not possible using conventional methods.
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- Gabrielsson, S, et al.
(författare)
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Influence of atopic heredity on IL-4-, IL-12- and IFN-gamma-producing cells in in vitro activated cord blood mononuclear cells
- 2001
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 126:3, s. 390-396
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Tidskriftsartikel (refereegranskat)abstract
- Several reports have claimed that there is a greater risk for a child with an atopic mother to develop allergy as compared to a child with an atopic father. This suggests that the fetal environment during pregnancy might be of importance for the development of atopic disease. Both proliferative and cytokine responses have been detected in cord blood mononuclear cells (CBMC) after stimulation with allergens, suggesting allergen priming already in utero. The aim of this study was to investigate whether the atopic status of the mother influences cytokine production by CBMC. We compared interleukin (IL)-4, IL-12 and interferon (IFN)-γ-producing CBMC from children with double atopic heredity (dh), maternal atopic heredity only (mh) or no atopic heredity (nh). CBMC were stimulated in vitro with allergens (birch, ovalbumin and cat), phytohaemagglutinin (PHA) or purified protein derivative (PPD) and cytokine-producing cells were measured by the enzyme-linked immunospot assay. In response to PHA, the frequency of IL-4-producing cells, as well as the ratio of IL-4/IFN-γ-producing cells, were significantly higher in the dh group compared to the nh group. High numbers of IL-12-producing cells in response to allergens were detected, significantly highest in the nh group, followed by the dh and mh groups. Our results suggest that there is a stronger Th2 bias after in vitro stimulation of CBMC from children with atopic heredity, as reflected by higher IL-4/IFN-γ ratios in response to PHA, and lower numbers of IL-12-producing cells after allergen stimulation. Whether these differences influence later allergy development will be evaluated when the atopic status of the children is assessed at 2 years of age.
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