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Objective: To explore the role and mechanism of SIRT1 (Sirtuin1) in the differentiation of adipocyte., Methods: SIRT1(-/-) mice with C57BL/6J gene background were generated and litter-mate wild-type (WT) mice were used as controls. Body weight and fat content were detected and their epididymal fat pads were collected at 28 weeks old of age. The tip part of epididymal fat tissue was incubated in phosphate buffered saline (PBS) containing both BODIPY 558/568 (5 µmol/L in PBS) for adipocytes and isolectin Alexa Fluor 488 (40 µg/ml in PBS) for endothelial cells overnight. The stained cells were then visualized under confocal microscope.Reconstruction of 3D data sets was accomplished with image processing software Imaris.Immunohistochemistry was used to detect the protein level of endothelial cell marker CD31.Hematoxylin and eosin staining was performed for fixed epididymal fat tissue. Mouse embryonic fibroblast (MEF) cells were prepared from 13-14 days embryos of SIRT1(-/-) or WT mice and differentiated into adipocytes. Then oil-red O staining was performed., Results: Compared with wild-type controls, both body weight (WT 42.1 g ± 1.6 g vs SIRT1(-/-) 25.4 g ± 1.0 g, P < 0.05) and epididymal fat mass (WT 13.4 g ± 1.0 g vs SIRT1(-/-) 7.8 g ± 0.5 g, P < 0.05) were much smaller in the SIRT1(-/-) mice. HE staining of fat tissue exhibited a significant reduction in adipocyte size and extracellular matrix in SIRT1(-/-) mice.However, the adipogenesis ability of MEF cells was significantly enhanced in vitro in SIRT1(-/-) MEF cells.Further study found that the density of vascular network decreased by 50% in the tip portion of epididymal fat pads of SIRT1(-/-) mice (capillary density:WT 2.92% ± 0.03% vs SIRT1(-/-) 1.34% ± 0.02%, P < 0.05). CD31, a cellular marker of decreased angiogenesis, decreased significantly in epididymal fat pads of SIRT1(-/-) mice., Conclusion: SIRT1 knockout impairs adipocyte differentiation in SIRT1(-/-) mice with C57BL/6J gene background through reduced angiogenesis but not adipogenesis.

Objective: To explore the effect of early insulin therapy on sterol regulatory element binding protein 1 (SREBP1) pathway and lipid accumulation in liver of type 2 diabetic rats (DM)., Methods: A high-fat diet plus a low-dose of streptozotocin (STZ) was administered to the Sprague-Dawley (SD) rats to create a type 2 diabetic animal model. Then the rats were divided into 3 groups: normal control (NC), DM (untreated diabetic rats) and INS (a 3-week treatment of NPH insulin initiated from day 3 of STZ injection). Insulin was delivered daily by a 3-week subcutaneous injection (6 - 8 U/day). Liver homogenate was prepared. The protein levels of ER stress marker immunoglobulin binding protein (Bip), oxygen-regulated protein 150 (ORP150), insulin-induced gene 1 (Insig1), SREBP1 and nuclear SREBP1 (nSREBP1) were assayed by Western blot. Adipose tissue mass was measured., Results: In the DM group, ER (endoplasmic reticulum) stress marker Bip and ORP150 were up-regulated (0.67 ± 0.02 vs 0.43 ± 0.01 for Bip; 1.11 ± 0.04 vs 1.83 ± 0.03 for ORP150, P < 0.05 for both) and Insig1 decreased (0.25 ± 0.02 vs 0.80 ± 0.07, P < 0.05). And the expressions of SREBP1 and nSREBP1 were elevated (1.03 ± 0.14 vs 0.41 ± 0.01 for SREBP1; 3.63 ± 0.77 vs 0.96 ± 0.20 for nSREBP1, P < 0.05 for both) in comparison with the normal control rats. In the INS group, all aforementioned changes became attenuated or reversed (0.41 ± 0.04 vs 0.67 ± 0.02 for Bip; 1.83 ± 0.03 vs 1.11 ± 0.04 for ORP150; 0.43 ± 0.02 vs 0.25 ± 0.02 for Insig1; 0.46 ± 0.01 vs 1.03 ± 0.14 for SREBP1; 1.65 ± 0.18 vs 3.63 ± 0.77 for nSREBP1, P < 0.05 for all). Furthermore, adipose tissue mass increased (22.4 g ± 3.6 g vs 12.0 g ± 2.6 g, P < 0.05)., Conclusion: The early insulin therapy induces a fat redistribution from liver to adipose tissue. The mechanism is probably through a reduction of ER stress and a down-regulated pathway of SREBP1 in liver of diabetic rats.

Left ventricular (LV) diastolic filling was examined by Doppler echocardiography in 239 patients with essential hypertension and 100 normal subjects. The Doppler study showed an inverse correlation between age and early diastolic peak velocity (PVE, r-0.201, P less than 0.05) [and a positive correlation between age and late diastolic peak velocity (PVA, r = 0.202, P less than 0.05) in normal subjects. Isovolumic relaxation time and late diastolic filling time were prolonged, PVA, A/E and Ai elevated, PVE, E/A and Ei/Ai as well as total filling time decreased in patients with hypertension as compared with the values found in the normal subjects (P less than 0.05 to 0.01). The results showed definite impairement of LV diastolic function in hypertensive patients. PVA correlated positively with systolic blood pressure (r = 0.68, P less than 0.01) and modestly with left atrial dimension in the hypertensives. No significant differences were found in FS and EF between the two study populations, indicating that LV filling abnormalities may occur early in patients with hypertension, even at a time when systolic performance has not yet been affected.