Overexpression of PPARγ induces adipogenic steatosis in mouse primary hepatocytes / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of PPARγ overexpression on steatosis in mouse primary hepatocytes.</p><p><b>METHODS</b>Primary hepatocytes isolated from C57BL/6J mice were infected with either Ad/LacZ or Ad/PPARγ for 48 h. Steatosis of the primary hepatocytes was checked by Oil Red O staining. The mRNA and protein expression of adipocyte-specific genes PPARγ, aP2 and CideA were analyzed by using RT Real-time PCR and Western Blot.</p><p><b>RESULTS</b>Primary hepatocytes were small and even. Hepatocyte nuclei were round with dispersed chromatin and prominent nucleoli. Accumulated lipid droplets were observed in Ad/PPARγ-infected hepatocytes, but in Ad/LacZ-infected hepatocytes. Moreover, compared with Ad/LacZ-infected hepatocytes, the mRNA expression of PPARγ, aP2, FGF21 and CideA in Ad/PPARγ-infected hepatocytes were significantly induced, the protein expression of PPARγ and its target aP2 strongly increased.</p><p><b>CONCLUSION</b>over expression of PPARγ induces adipogenic steatosis in mouse primary hepatocytes.</p>

Hyperlipidemia in hepatic MED1 deficient mice in response to fasting / 生物工程学报

MED1 is a key transcription co-activator subunit of the Mediator complex that is essential for RNA polymerase II-dependent transcription. MED1 functions as a co-activator for PPARs and other nuclear receptors and transcription factors, and plays an important role in lipid metabolism. To examine how MED1 might affect plasma lipids, plasma triglyceride, cholesterol levels, and lipoprotein profiles, were measured in MED1(deltaLiv) mice fasted for 24, 48 and 72 hours. Histological changes in liver sections from MED1(deltaLiv) mice after 72 hours of fasting were also examined using H&E staining. There was no fat accumulation in livers of MED1(deltaLiv) mice compared to MED1(fl/fl) and PPARalpha -/- control mice after 72 hours of fasting. Compared with MEDl(fl/fl) mice, plasma triglycerides in MED1(deltaLiv) mice were significantly increased after 24, 48 and 72 hours of fasting, and plasma cholesterol was significantly increased after 48 and 72 hours of fasting. Lipoprotein profiles were similar in fed MED1(fl/fl) and MED1(deltaLiv) mice. However, very low density lipoprotein (VLDL) was significantly increased in MED1(deltaLiv) mice after 24 hours of fasting. We conclude that, hyperlipidemia in MED1(deltaLiv) mice in response to fasting is due to the accumulation of VLDL, which suggests that MED1 plays a pivotal role in the regulation of plasma triglyceride and cholesterol levels.

A study of the time-dependent changes in myocardial ischemia/reperfusion injury / 中国病理生理杂志

The time-dependent changes in myocardio membrane system during ischemia/reperfusion injury were studied with ligature of the left ventricular branch of coronary artery in rabbit. The permeability of cardiac membrane system being tested by using lanthanum tracer technique and stereological methods. Lanthanum granules were observed in the sarplacosma and sarccpiasmic tubes especially at ischemia for 20min. The pecmeability of membrane system for La~(+++) was more marked when hearts were reperfused for 20min. With the increase in time of ischemia, the changes became more and more serious. A lot of lanthanum granules were entered into mitochondria when the hearts were reperfused after 40min ischemia. There were neither intact mitichondria nor lanthanum granules in mitochondria observed when the hearts were reperfused after 60min ischemia. The structural changes were irreversible at this stage of reperfusion The results of our study indicated that the changes of permeability of cardiac cell for La~(+++) in ischcmia/reperfusion are time-dependent, 40min ischemia is the demarcation line between the reversible and irreversible injury during reperfusion. On the basis of our experiment, we like to propose a new conception of reversible and irreversible injury of reperfusion.