| 2. |
- Hansen, Jacob B, et al.
(författare)
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Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation.
- 2004
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 101:12, s. 4112-7
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Tidskriftsartikel (refereegranskat)abstract
- Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo fibroblasts (MEFs) and white preadipocytes by expression of simian virus 40 large T antigen results in the expression of the brown fat-specific uncoupling protein 1 (UCP-1) in the adipose state. Retinoblastoma gene-deficient (Rb-/-) MEFs and stem cells, but not the corresponding wild-type cells, differentiate into adipocytes with a gene expression pattern and mitochondria content resembling brown adipose tissue. pRB-deficient MEFs exhibit an increased expression of the Forkhead transcription factor Foxc2 and its target gene cAMP-dependent protein kinase regulatory subunit RIalpha, resulting in increased cAMP sensitivity. Suppression of cAMP-dependent protein kinase activity in Rb(-/-)MEFs blocked the brown adipocyte-like gene expression pattern without affecting differentiation per se. Immunohistochemical studies revealed that pRB is present in the nuclei of white but not brown adipocyte precursor cells at a developmental stage where both cell types begin to accumulate lipid and brown adipocytes express UCP-1. Furthermore, pRB rapidly undergoes phosphorylation upon cold-induced neodifferentiation and up-regulation of UCP-1 expression in brown adipose tissue. Finally, down-regulation of pRB expression accompanies transdifferentiation of white into brown adipocytes in response to beta3-adrenergic receptor agonist treatment. We propose that pRB acts as a molecular switch determining white vs. brown adipogenesis, suggesting a previously uncharacterized function of this key cell cycle regulator in adipocyte lineage commitment and differentiation.
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| 3. |
- Rosendahl, Lars, 1971-, et al.
(författare)
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Increase in muscle nociceptive substances and anaerobic metabolism in patients with trapezius myalgia : microdialysis in rest and during exercise
- 2004
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 112:3, s. 324-334
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Tidskriftsartikel (refereegranskat)abstract
- Local metabolic changes are suggested to be involved in muscle pain development in humans. Nineteen women with chronic work-related trapezius myalgia (TM) and 20 healthy female controls (CON) were studied during baseline rest, 20 min repetitive low-force exercise, and 120 min recovery. Interstitial serotonin (5-HT), glutamate, lactate, pyruvate, and blood flow were determined by microdialysis in the trapezius muscle. Baseline pressure pain threshold (PPT) was lower (143+/-18 (TM) vs. 269+/-17 (CON) kPa) (mean +/- SEM), pain intensity (visual analogue scale, VAS) higher (33+/-5 vs. 2+/-1 mm), muscle 5-HT higher (22.9+/-6.7 vs. 3.8+/-1.3 nmol/l), and glutamate higher (47+/-3 vs. 36+/-4 mumol/l) in TM than in CON (all P<0.05), whereas muscle blood flow was similar in groups. Furthermore, muscle pyruvate was higher (180+/-15 vs. 135+/-12 mumol/l) and lactate higher (4.4+/-0.3 vs. 3.1+/-0.3 mmol/l) in TM than in CON (P<0.001). In response to exercise, VAS and glutamate increased in both TM and CON (all P<0.05). In TM only, lactate and pyruvate increased significantly (P<0.02), whereas blood flow increased to similar levels in both groups. During the initial 20 min recovery period, blood flow remained increased in TM (P<0.005) whereas it decreased to baseline levels in CON. In conclusion, patients with chronic work-related TM have increased levels of muscle 5-HT and glutamate that were correlated to pain intensity (r=0.55, P<0.001) and PPT (r=-0.47, P<0.001), respectively. In addition, TM was associated with increased anaerobic metabolism, whereas a normal rise in blood flow was seen with exercise. These findings indicate that peripheral nociceptive processes are active in work-related TM.
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