多不饱和脂肪酸对基因表达的调控机制

多不饱和脂肪酸(PVFAs)不仅是细胞结构和功能的重要组成成分,而且对细胞生长、代谢、分化中的基因起调控作用。研究表明PUFAs可通过与肝脏核因子-4α、肝脏X受体α,β、过氧化物酶体增殖物激活受体(PPARs)等核受体直接作用,或与转录因子固醇调节元件结合蛋白1,2间接作用,以多种机制在分子水平上调节相关酶的基因转录。深化PUFAs基因调控机制的研究,对于营养、健康和医疗具有重要意义。     

PPARs激动剂与骨质疏松症

过氧化物酶增殖激活受体(Peroxisome proliferator activated receptors,PPARs)是核激素受体家族中的配体激活受体,包括3种亚型：PPARα、PPARβ/δ和PPARγ,具有增强机体对胰岛素敏感性,调节体内糖平衡以及脂肪的分化、生成等多种生物学功能。PPARγ激动剂作为胰岛素增敏剂治疗2型糖尿病的重要药物,可引起糖尿病性骨质疏松症(Diabetic Osteoporosis,DO),DO发病机制复杂,致残、致死率高。本文主要对PPARs激动剂在治疗糖尿病中对骨的影响进行综述。     

Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice

Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized (“postmenopausal”) females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor α (ERα) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A11 protein, serum 17β-estradiol levels, and WAT ERα expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women.     

过氧化物酶体增殖物激活受体的医学重要性

过氧化物酶体增殖物激活受体(peroxisome prolifera(?)o(?)s activated receplors,PPARs)是Ⅱ型受体超家族成员,有PPAR(α)、PPAR(β)、PPAR(γ)3个亚型,它们参与脂类代谢、线粒体代谢、细胞分化、细胞周期和细胞凋亡的调节,对研究肥胖和糖尿病及肿瘤的发病机制有十分重要的意义。     

Antidiabetic,antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats

Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies.Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60 mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10 μM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p < 0.05) were diminished. Moreover, IL-1β and IL-18 expression was significantly decreased in adipose tissue (p < 0.05); meanwhile adiponectin was significantly overexpressed (p < 0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p < 0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p < 0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα.     

代谢性核受体及其与代谢综合征的关系

代谢性核受体是一组与代谢调节相关的配体激活核受体转录因子,主要包括脂质过氧化物体增殖物激活受体(PPARs)、肝X受体(LXRs)和法尼酯衍生物X受体(FXRs)3种。它们在胰岛素敏感性、脂肪生成、脂质代谢、能量代谢、血压调节、炎症、细胞生长和分化等过程中起着关键的调节作用,因而近年来倍受关注。越来越多的研究表明这3种核受体不仅与代谢综合征,包括胰岛素抵抗、糖耐量受损2、型糖尿病、肥胖、高脂血症、高血压和微白蛋白尿之间存在密切的关系,也在动脉粥样硬化的发生及发展中有重要的作用。本文就代谢性核受体的生物学活性和生理功能作一简述,并对其在代谢综合征发病机制中的作用进行重点讨论。     

The role of metabolic syndrome variant in the malignant tumors progression

Metabolic syndrome (MS) is one of the leading risk factors for the development of some common cancers (endometrial cancer, postmenopausal breast cancer, colorectal cancer). Currently, a drug-induced metabolic syndrome related with androgen deprivation therapy in patients with prostate cancer represents a serious medical problem. Not only MS, or its individual components, but MS variants with different levels of leptin, adiponectin, visfatin, resistin are associated with tumor invasion, metastasis and survival rates in patients with MS-associated malignancies.     

Increase of myocardial performance by Rhodiola–ethanol extract in diabetic rats

Ethno pharmacological relevance

Rhodiola rosea (also known as golden root or roseroot) is a perennial plant of the Crassulaceae family that grows in the Arctic and in the mountainous regions of Europe, Asia, and North America. The rhizome and roots of this plant have been long used as traditional medicine in Eastern Europe and Asia for enhancing physical and mental performance.

Aim of the study

The present study is designed to investigate the cardiac action of Rhodiola–ethanol extract in streptozotocin-induced diabetic rats (STZ-diabetic rats) with heart failure.

Materials and methods

Diabetes was induced in Wistar rats by injection of streptozotocin. We measured the changes of body weight, water intake, and food intake in three groups of age-matched rats; the normal control received vehicle, STZ-diabetic rat received Rhodiola–ethanol extract or vehicle. Cardiac output, heart rate, blood pressure, and hemodynamic dP/dt in addition to plasma insulin and glucose level were also determined. The mRNA and protein levels of PPARδ were measured using real-time PCR and Western blotting, respectively.

Results

Food intake, water intake and blood glucose were raised in STZ-diabetic rats showing lower body weight and plasma insulin, as compared with the control. Also, cardiac output, heart rate, blood pressure and hemodynamic dP/dt were markedly reduced in STZ-diabetic rats indicating the heart failure physiologically. After a 21-day treatment with Rhodiola–ethanol extract, cardiac output was raised in STZ-rats while the diabetic parameters were not modified. The PPARδ expression of both mRNA and protein was markedly elevated in the heart of STZ-rats receiving treatment with Rhodiola–ethanol extract. Also, the increased phosphorylation level of cardiac troponin-I was restored by this treatment with Rhodiola–ethanol extract. Otherwise, increase of cardiac output by Rhodiola–ethanol extract was blocked by antagonist of PPARδ in STZ-diabetic rats.

Conclusions

Our results suggest that ethanol extract of Rhodiola has an ability to increase the cardiac output in STZ-diabetic rats showing heart failure. Also, increase of PPAR-δ is responsible for this action of Rodiola–ethanol extract.