Effect of Atglistatin on PA-induced VSMCs proliferation and ATGL expression / 中国临床药理学与治疗学

AIM: With building a proliferation model of PA-induced VSMC, the effect of ATGL, a key fat metabolism enzyme, on the phenotype transformation of VSMC was preliminarily explored. METHODS: 40 μmol/L Atglistatin was added to the proliferation model of VSMC induced by PA (50 μmol/L, 100 μmol/L, and 200 μmol/L, respectively) at separately administered concentrations, and cell viability and cell proliferation were detected by CCK-8 and EDU; cell migration ability was detected by scratch assay; oil red staining was used to detect the accumulation of lipid droplets in VSMC was detected by oil red staining; the effects of PA on ATGL as well as the effects of smooth muscle contraction phenotype proteins were examined by Western blot. RESULTS: PA at a concentration of 100 μmol/L could significantly induce VSMC proliferation, promote lipophagy and increase lipid droplet accumulation in VSMC; meanwhile, Atglistatin could exacerbate these changes caused by PA and increase lipid droplet accumulation in VSMC. CONCLUSION: Atglistatin exacerbates PA-induced VSMC proliferation and increases VSMC lipid droplet accumulation, and exacerbates transformation of proliferative phenotype of VSMC.

Therapeutic regulation of autophagy in hepatic metabolism

Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ that governs body energy metabolism. Autophagy's role in hepatic energy regulation has just begun to emerge and autophagy seems to have a much broader impact than what has been appreciated in the field. Though classically known for selective or bulk degradation of cellular components or energy-dense macromolecules, emerging evidence indicates autophagy selectively regulates various signaling proteins to directly impact the expression levels of metabolic enzymes or their upstream regulators. Hence, we review three specific mechanisms by which autophagy can regulate metabolism: A) nutrient regeneration, B) quality control of organelles, and C) signaling protein regulation. The plasticity of the autophagic function is unraveling a new therapeutic approach. Thus, we will also discuss the potential translation of promising preclinical data on autophagy modulation into therapeutic strategies that can be used in the clinic to treat common metabolic disorders.

Association between the polymorphism of PNPLA2 gene and the risk of ischemic stroke in type 2 diabetic patients in Chinese Han Population / 中国临床药理学与治疗学

AIM: To investigate the association between the polymorphism of the fatty triglyceride lipase gene (PNPLA2) rs1138693 (T>C) and the risk of ischemic stroke in type 2 diabetic patients in China. METHODS: A total of 368 Chinese patients with type 2 diabetes mellitus (T2DM) (139 T2DM ischemic stroke patients and 229 T2DM non-ischemic stroke patients were included as the control group) were included in this case-control study. PNPLA2 rs1138693 (T>C) was genotyped by real-time polymerase chain reaction (PCR) and statistically analyzed by SPSS 20.0. RESULTS: Significant differences were observed in age, sex, blood pressure and homocysteine levels between the control group and the ischemic stroke group (P<0.05). The CC genotype frequency and C allele frequency of PNPLA2 rs1138693 in the ischemic stroke group were significantly lower than those in the control group (genotype frequency: P=0.033; allele frequency: P=0.011). Logistic regression analysis revealed that allele C of PNPLA2 rs1138693 was a protective factor for progression to ischemic stroke in T2DM patients under the additive, dominant and recessive genetic models (P<0.05). CONCLUSION: The PNPLA2 gene rs1138693 is related to the susceptibility of Chinese T2DM patients to ischemic stroke, and the T2DM patients with allele C of rs1138693 are less likely to develop ischemic stroke.

Discussion on medicinal attribution of Descurainia sophia and its nature and flavor splitting components based on typical energy metabolism of heat syndrome animal models / 中草药

Objective: The relevant indicators of energy metabolism in rats with heat syndrome were tested to verify the medicinal properties of Descurainia sophia and its nature and flavor splitting components, in order to explain the cold and heat properties of D. sophia and its splitting components. Methods: Healthy male Sprague-Dawley rats were randomly divided into normal control group (NC), model group (M), water extract of gardenia (DS), flavonoid glycosides composition of D. sophia (FG), flavonoid aglycone composition of D. sophia (FA), oligosaccharide resolution component group (Oli), gardenia polysaccharide decomposition component group (Pol), and D. sophia fatty oil component separation group (FO). The model of heat syndrome was established by intragastric administration of Euthyrox (120 mg/kg). After 15 days of continuous administration, blood was taken from the abdominal aorta and the liver and heart were taken to detect the indicators related to the energy metabolism of the substance. The enzyme expression of glucokinase (GCK) and fructose phosphokinase (PFK-1), phosphoglycerate kinase (PGK), pyruvate kinase (PK), pyruvate dehydrogenase (PDH), acetyl-CoA, citrate synthase (CS), isocitrate dehydrogenase (ICD), alpha-ketoglutarate dehydrogenase (alpha-KGDHC), fumarate (FUM), glycogen phosphorylase (PYGL), glycogen synthase kinase-3 (GSK-3), adipose triglyceride lipase (ATGL), cytochrome C reductase (CCR), cytochrome C oxidase (COX), ATP synthase (ATPs), adenylate kinase (ADK), Na+ K,+-ATPase and the content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide (NADH) were determined. Results: Compared with NC group, the weight of M group rats was decreased significantly (P < 0.01). Compared with M group, the body weights of rats in DS, FG, FA, Pol and tFO groups were significantly or highly significantly increased (P < 0.05, 0.01). Compared with NC group, the number of spontaneous activities in M group was increased significantly (P < 0.01) within 5 min, and the number of locomotor activities of each group within 5 min after administration was significantly decreased (P < 0.01). Compared with NC group, the levels of GCK, PFK-1, PK, PGK, PDH, acetyl-CoA, CS, ICD, α-KGDHC, FUM, PYGL, GSK-3, ATGL, ATP, CCR, COX, ATPs, ADK, Na+ K,+-ATP, NADH expression or content in M group of rats were significantly increased (P < 0.05, 0.01), the content of ADP, NAD+ and NAD+/NADH was decreased (P < 0.05, 0.01). After administration, the expression level of material energy metabolism of the rats in each group was significantly or extremely significantly reduced compared with the M group (P < 0.05, 0.01). Conclusion: D. sophia can improve the state of the energy-metabolism related indicators of the rats in the heat syndrome model group. It is verified that D. sophia nature and flavor splitting components show the cold (cool) properties. From the side, it reflects the mechanism of "treating heat with cold drug" is related with the substance energy metabolism.

Research progress of pigment epithelium-derived factor / 医学研究生学报

Pigment epithelium-derived factor(PEDF)is an endogenously produced protein widely expressed throughout the human body,which exhibits multiple and varied biological actions.Over the past few years,PEDF has been described as a multifaceted protein with anti-angiogenic, neurotrophic, neuroprotective, and anti-permeability.PEDF effectively inhibits vascular endothelial growth factor(VEGF)-driven angiogenesis and vascular permeability by regulating the intracellular proteolysis of VEGF receptors in re -cent reports.Moreover,PEDF can inhibit the occurrence of neural degenerative diseases through a variety of signaling pathways.The aim of the present review is to discuss the varied biological actions of PEDF and to identify the possible molecular mechanism underly -ing its effects.

Silencing ATGL gene expression inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells / 肿瘤

Objective: To investigate the expression of adipose triglyceride lipase (ATGL) in hepatocellular carcinoma (HCC) tissues and cell lines, and to explore the role of ATGL in proliferation, migration and invasion of HCC cells. Methods: The expression of ATGL protein in 57 pairs of HCC tissues and their corresponding adjacent normal liver tissues as well as 12 kinds of HCC cell lines was detected by Western blotting. The recombinant lentiviruses (GV248-shATGL-1, -2, and -3) carrying specific shRNAs targeting ATGL gene were infected into HCC cell lines Huh7 and MHCC-97L. The negative control shRNA-carried lentivirus (GV248-shNC) was used as the negative control. The efficiency of ATGL gene-silencing was verified by real-time fuorescent quantitative PCR and Western blotting. Furthermore, the effects of ATGL gene-silencing on proliferation, migratory and invasive abilities of HCC cells were detected by CCK-8 assay and Transwell chamber assay, respectively. Results: Compared with the corresponding adjacent normal liver tissues, the expression of ATGL protein was significantly up-regulated in 49% (28/57) and down-regulated in 28% (16/57) of HCC tissues. There was no significant difference in ATGL expression between HCC tissues and the corresponding adjacent normal liver tissues in 23% (13/57) of HCC cases. The proliferation of Huh7 and MHCC-97L cells was suppressed after ATGL gene-silencing (both P<0.05). And the migration and invasion abilities of Huh7 and MHCC-97L cells with ATGL gene-silencing were significantly decreased as compared with those in the negative control group (all P<0.01). Conclusion: The expression of ATGL is commonly up-regulated in HCC tissues. ATGL genesilencing can suppress the proliferation, migration and invasion of HCC cells.

Relationship between serum ATGL and inflammatory factors in patients with coronary heart disease / 国际检验医学杂志

Objective To investigate the relationship between serum three triacylglycerol lipase (ATGL) and inflammatory factors in patients with coronary atherosclerotic heart disease (CHD).Methods 135 cases of CHD patients,and 50 healthy people were enrolled in the study.CHD patients were divided into stable angina pectoris (SAP) group (53 cases),unstable angina pectoris (UAP) group(46 cases) and acute myocardial infarction (AMI) group (36 cases) according to relevant diagnostic criteria.The serum levels of ATGL,tumor necrosis factor (TNF-α),interleukin-6(IL-6), interleukin-10(IL-10),1,25 dihydroxy vitamin D3[1,25(OH)2D3] were measured by ELISA, and statistical treatment was performed.Results The levels of ATGL,1,25(OH)2D3 in CHD group were lower than that in control group,and the levels of TNF-α,IL-6 and IL-10 were higher than those of control group(P<0.05).Comparison among different clinical types of CHD patients showed that ATGL,1,25 (OH)2D3 levels of AMI group were significantly lower than those of SAP group and UAP group,while TNF-α,IL-6 and IL-10 were higher than those of SAP group and UAP group(P<0.05);the levels of ATGL,1,25(OH)2D3 in UAP group were lower than those in SAP group,and TNF-α and IL-10 were higher than those in SAP group(P<0.05).Spearman correlation analysis showed that in the CHD group the serum levels of ATGL negatively correlated with TG,LDL-C,LP (a),TNF-α,IL-6,IL-10(r=-0.289,-0.227,-0.359,-0.243,-0.205,-0.337,P<0.05),while positively correlated with age,HDL-C,1,25(OH)2D3(r=0.267,0.356,0.229,P<0.05).Conclusion The ATGL levels in patients with CHD decreases with the increase of inflammatory factors,and plays a certain anti-inflammatory role in the progression of CHD.It can be used as a monitoring indicator to reflex the progress of CHD.

Lipolysis and lipases in white adipose tissue – An update

Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.

Effects of pioglitazone on the expression of adipose triglyceride lipase in obese rats / 中华内分泌代谢杂志

To detect the effects of pioglitazone on adipose triglyceride lipase (ATGL) in adipose,liver,and muscle of high-fat diet-induced obese rats.Insulin resistance aud decreased expression of adipose triglyceride lipase were found in the adipose,liver,and muscle tissues.Pioglitazone may improve insulin sensitivity and ameliorate ATGL expression in tissues of high-fat diet-induced obese rats.