Preliminary adipose removal did not prevent diet-induced metabolic disorders in mice / 中华医学杂志(英文版)

BACKGROUND@#Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders.@*METHODS@#Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders.@*RESULTS@#In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups.@*CONCLUSIONS@#Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.

Nicorandil improves cognitive dysfunction in mice with streptozotocin-induced diabetes / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes.</p><p><b>METHODS</b>C57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined.</p><p><b>RESULTS</b>Compared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue.</p><p><b>CONCLUSION</b>Nicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by increasing GIP and GLP-1 contents in the hippocampus and promoting antioxidation to relieve hippocampal injury.</p>

Effects of CCN5 overexpression on the expression of alpha-SMA and collagen I in hepatic stellate cells and its mechanism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between connective tissue growth factor (CCN5) and hepatic stellate cell (HSC) activation as well as the mechanism of action.</p><p><b>METHODS</b>As the research object, LX-2 cells were stimulated with transforming growth factor-beta1 ( TGF-(beta1), and the protein expression levels of CCN5 and CCN2 were determined by Western blot; Hepatocyte high expression system of CCN5 was constructed and transfected hepatic stellate cells (HSC) to make CCN5 overexpression; The expression levels of alpha-smooth muscle actin (alpha-SMA) and collagen I were determined by RT-PCR and Western blot. To further study its mechanism of action, Smad2 and phosphorylation level of Smad2 were determined by RT-PCR and Western blot.</p><p><b>RESULTS</b>Under normal circumstances, CCN2 expression levels were much higher than CCN5 in LX-2 cells, while CCN2 expression was significantly higher than CCN5 if LX-2 cells were stimulated by TGF-beta1. However, there was no change for CCN5. Compared with the control group and the vector group, CCN5 was successfully overexpressed in the transfection group, and mRNA and protein levels of alpha-SMA and collagen I were significantly decreased (P < 0.01). Meanwhile, phosphorylation level of Smad2 was also significantly decreased (P < 0.01).</p><p><b>CONCLUSION</b>CCN5, which has the function that inhibits HSC activation, has the opposite role compared with CCN2, therefore, a new idea was proposed for the prevention and treatment of liver fibrosis.</p>