Metabolic syndrome (MetS) can lead to increase of insulin resistance (IR) and visceral adipose tissue production of adipocytokines. 6-gingerol is known to have antioxidant and anti-inflammatory activities. Aim of this study is to investigate the effects of 6-gingerol on high-fat high-fructose (HFHF) diet-induced weight gain and IR in rats through modulation of adipocytokines. To induce MetS, male Sprague-Dawley rats were fed with a HFHF diet for 16 weeks and at Week 8, single-dose low-dose streptozotocin (22 mg/kg) were intraperitoneally injected. After 8 weeks of HFHF diet feeding, the rats were treated orally with 6-gingerol (50, 100, and 200 mg/kg/day) once daily for 8 weeks. At the end of the study, all animals were terminated, serum, liver, and visceral adipose tissues were harvested for biochemical analysis including the measurements of total cholesterol, triglycerides, HDL-cholesterol, fasting plasma glucose, insulin, leptin, adiponectin, proinflammatory cytokines (TNF-α and IL-6) and liver and adipose tissue histopathology. Biochemical parameters namely serum total cholesterol (243.7 ± 127.6 vs 72.6 ± 3 mg/dL), triglycerides (469.2 ± 164.9 vs 49.3 ± 6.3 mg/dL), fasting plasma glucose (334 ± 49.5 vs 121 ± 8.5 mg/dL), HOMA-IR (0.70 ± 0.24 vs 0.32 ± 0.06), and leptin (6.19 ± 1.24 vs 3.45 ± 0.33 ng/mL) were significantly enhanced, whereas HDL-cholesterol (26.2 ± 5.2 vs 27.9 ± 1.1 mg/dL) and adiponectin level (14.4 ± 5.5 vs 52.8 ± 10.7 ng/mL) were lowered in MetS vs normal control. Moreover, MetS were marked a significant increase in body weight and proinflammatory cytokines. Treatment with 6-gingerol dose-dependently restored all of those alterations towards normal values as well as the accumulation of lipid in liver and adipose tissues. These findings demonstrate that 6-gingerol, in a dose-dependent mode, showed capability of improving weight gain and IR in MetS rats through modulation of adipocytokines.

Worldwide statins are considered to be the first-line pharmacological treatment for dyslipidemia and reducing the risk of coronary heart disease. However, recently various studies have shown its adverse effect on glucose control among diabetic patients and the U.S. Food and Drug Administration have revised statin drug labels to include information that increases in fasting serum glucose and glycated hemoglobin levels have been reported. This systematic review objective is to evaluate the risks and benefits of statins in glucose control management of type 2 diabetes patients based on the 44 published journal articles included and obtained through MEDLINE full text, PubMed, Science Direct, Pro Quest, SAGE, Taylor and Francis Online, Google Scholar, High Wire, and Elsevier Clinical Key. Statins were found to affect glucose control through several ways, namely, by affecting insulin production and secretion by β-pancreatic cells, insulin resistance, insulin uptake by the muscles and adipocytes and production of adipokines. Current evidence available shows that most of the statins give unfavorable side effects with regards to glucose control among diabetic patients. A dose-dependent and time-dependent effect was also observed in some statins which may be present among other statins as well.

Apelin is a novel adipokine identified as an endogenous ligand of the specific orphan receptor APJ. Among the various isoforms of apelin, an increase in the apelin-36 plasma level has been associated with oxidative stress, and this isoform has various biological effects, such as positive inotropic, vasodilatory, and antiatherosclerotic effects. Therefore, apelin-36 may be used as a biomarker of heart failure (HF). Advances in the understanding of the molecular mechanisms underlying HF cannot be achieved without the use of animal models. However, it is unclear whether chronic systemic hypoxia can cause HF in rats. The present study aimed to determine whether chronic systemic hypoxia can cause HF in rats and whether apelin-36 can be used as a biomarker of HF. The study included Sprague–Dawley rats. The rats were randomly divided into seven groups (n = 4). One of the groups was a control group, and the six other groups were exposed to hypoxia (8% O2) for different durations (6 hours, 1 day, 3 days, 5 days, 7 days, and 14 days). The exposure groups showed ventricular hypertrophy accompanied by myocardial structural damage, which indicated ventricular remodeling. In addition, the exposure groups showed elevated apelin-36 plasma levels and signs of oxidative stress. Moreover, gel electrophoresis of heart tissue showed five bands that corresponded to apelin isotypes, including apelin-36. In an experimental rat HF model with chronic systemic hypoxia, apelin-36 was elevated along with oxidative stress. Apelin-36 along with oxidative stress may serve as a biomarker of HF in this model.

Background: Liver is sensitive against hypoxia and hypoxia will stabilize HIF-1α. At the same time, hypoxia will produce reactive oxygen species (ROS) which can be scavenged by Cygb. The purpose of our study is to know, if normobaric hypoxia can induce Cygb expression and its association with HIF-1α stabilization.Methods: This is an experimental study using 28 male Sprague-Dawley rats, 150-200 g weight. Rats are divided into 7 groups: control group and treatment groups that are kept in hypoxic chamber (10% O2: 90% N2) for 6 hours, 1, 2, 3, 7 and 14 days. All rats are euthanized after treatment and liver tissue are isolated, homogenized and analyzed for oxidative stress parameter, expression of Cygb and HIF-1α.Results: Expression of Cygb mRNA and protein was increased on the day-1 after treatment and reach the maximum expression on the day-2 of hypoxia treatment. But, the expression was decreased after the day-3 and slightly increased at the day-14 of hypoxia. The correlation between expression of Cygb and oxidative stress parameter was strongly correlated. Cygb mRNA, as well as protein, showed the same kinetic as the HIF-1, all increased about day-1 and day-2.Conclusion: Systemic chronic hypoxia and/or oxidative stress up-regulated HIF-1α mRNA which is correlated with the Cygb mRNA and protein expression. Cygb mRNA as well as Cygb protein showed the same kinetic as the HIF-1, all increased about day-1 and day-2 suggesting that Cygb could be under the regulation of HIF-1, but could be controlled also by other factor than HIF-1.

The aim of this study was to investigate the influence of intermittent hypobaric hypoxia on the expression hypoxia adaptation proteins, namely hypoxia inducibla factor-1a (HIF-1a) and myoglobin (Mb). Twenty five male Sprague-Dawley rats were exposed to intermittent hypobaric hypoxia in a hypobaric chamber in Indonesian Air Force Institute of Aviation Medicine, for 49.5 minutes at various low pressure, 1 week interval for 4 times (day 1, 8, 15 and 22). HIF-1α and Mb protein were measured with ELISA. mRNA expression of Mb was measured with one step real time RT-PCR. HIF-1α protein levels increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p = 0.0437). mRNA expression and protein of Mb increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p = 0.0283; 0.0170), and both are strongly correlated (Pearson, r = 0.6307). The heart of rats adapted to intermittent hypoxia conditions by upregulation the expression of HIF-1a and myoglobin and then both return to normal level

Background: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α). The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unclear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise. Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium. Results: Both, HIF-1α protein and VEGF were increased (p < 0.05) in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66). Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35), while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73). The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59) in the aerobic group and strong in the anaerobic group (r = 0.69). Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise. (Med J Indones. 2012;21:133-40) Keywords: Exercise, HIF-1α, myocardium, VEGF