Adriamycin inhibits glycolysis through downregulation of key enzymes in Saccharomyces cerevisiae.

Adriamycin is a widely used drug for the treatment of various types of cancers, but its clinical application is limited because of irreversible dilated cardiomyopathy. The incidence of cardiomyopathy is a consequence of disrupted energy production, which could be related to the defects in glycogen, lipid and mucopolysaccharide metabolism. We explored the effect of Adriamycin on enzymes involved in glycolysis and apoptotic genes through molecular docking. We used Saccharomyces cerevisiae as model organism and studied the effect of Adriamycin on selected enzymes involved in glycolysis. The docking studies revealed that Adriamycin interacts with phosphofructokinase and enolase in an efficient manner. In phosphofructokinase, Adriamycin binds at the active site and with enolase the drug interacts at the cofactor-binding site (Mg2+) which might impair the activity of the enzyme. Gene expression studies revealed that Adriamycin causes the dysregulation of glycolysis through dysregulation of hexokinase, phosphoglycerate mutase, enolase and downregulation of pyruvate kinase. The drug shows a biphasic effect on the expression of genes enolase and pyruvate kinase. The impairment in glycolysis might reduce the ATP synthesis, and the cells might be deprived of energy. The condition is further worsened by elevated ROS levels triggering the cell to undergo apoptosis evidenced by downregulation of SOD and upregulation of BAX and caspase. In conclusion, our study reveals that Adriamycin impairs glycolysis and cause cell to undergo apoptosis due to oxidative stress in yeast cells.

Emu oil decreases atherogenic plaque formation in cafeteria diet-induced obese rats.

BACKGROUND: Atherosclerosis-induced coronary heart disease - caused by elevated levels of low-density lipoproteins (LDL) and inflammation - is one of the most prevalent diseases. Monounsaturated fatty acids are reported to prevent atherosclerosis; emu oil is a rich source of monounsaturated fatty acid, and we hypothesize that emu oil supplementation could lower inflammation and prevent atherosclerosis in diet-induced obese (DIO) animals. Male Wistar rats were randomly divided into five groups (n = 6), and fed with normal diet (chow pellet; ND), or with cafeteria diet (CD), or with CD along with emu oil supplementation at three different doses: ED1 (2 mL), ED2 (4 mL) and ED3 (8 mL) kg(-1) body weight (BW), respectively. RESULTS: After 12 weeks, the animals were sacrificed and serum was analysed for measuring lipid profile, C-reactive proteins, testosterone and luteinizing hormone. Histopathological studies were performed to observe atherogenic changes in thoracic aorta. Restoration of altered lipid and hormonal profiles, and inhibition of atherogenic changes in thoracic aorta, were observed with supplementation of emu oil, confirming its anti-atherosclerotic activity. CONCLUSION: The high content of oleic acid in emu oil could have orchestrated - either solely or in combination with linoleic and linolenic acids - causing the upregulation of testosterone biosynthesis and inhibition of atheromatous plaque formation in diet-induced obese animals. © 2015 Society of Chemical Industry.

Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The effects of actiponin was investigated, a heat-processed Gynostemma pentaphyllum extract, on body weight, fat loss, and metabolic markers of Korean participants in a 12-week, randomized, double-blind, placebo-controlled clinical trial. DESIGN AND METHODS: Obese participants (BMI ≥ 25 kg m(-2) and WHR ≥ 0.90 for male or WHR ≥ 0.85 for female) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 80 subjects were randomly divided into actiponin (n = 40, 450 mg day(-1) ) and placebo (n = 40) groups. Outcomes included measurement of efficacy (abdominal fat distribution, anthropometric parameters, and blood lipid profiles) and safety (adverse events, laboratory test results, electrocardiogram data, and vital signs). RESULTS: During 12-week of actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P = 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the actiponin group compared to the placebo group. No clinically significant changes in any safety parameter were observed. CONCLUSION: Our study revealed that actiponin is a potent antiobesity reagent that does not produce any significant adverse effects. These results suggest that actiponin supplementation may be effective for treating obese individuals.

Doxorubicin treatment inhibits PPARγ and may induce lipotoxicity by mimicking a type 2 diabetes-like condition in rodent models.

Doxorubicin-treated animals show elevated serum triglyceride and blood glucose levels. Adipocytes play an important role in buffering blood glucose and lipids. A raise in serum lipid level triggers adipogenesis in order to increase the lipid absorption capacity of adipose tissue. Doxorubicin inhibits adipogenesis through the down-regulation of PPARγ, a crucial component of the lipid metabolic pathway which controls the expression of glucose and fatty acid transporters. Doxorubicin-mediated down-regulation of PPARγ inhibits blood glucose and lipid clearance thereby causing hyperglycemia and hyperlipidemia resulting in lipotoxicity, glucotoxicity, inflammation and insulin resistance. Therefore we hypothesize that doxorubicin treatment could mimic a type 2 diabetic condition.

Anti-obesity effect of kimchi fermented with Weissella koreensis OK1-6 as starter in high-fat diet-induced obese C57BL/6J mice.

AIMS: In this study, we investigated the anti-obesity effects of kimchi (Korean traditional fermented vegetable) fermented either without starter culture or with a specific starter culture, Weissella koreensis OK1-6. METHODS AND RESULTS: C57BL/6J mice were divided into four groups (n = 7); normal diet, HF (high-fat diet), HF-KC (high-fat diet containing 3% kimchi manufactured without starter) and HF-KCO (high-fat diet containing 3% kimchi manufactured with the starter culture W. koreensis OK1-6). After 12 weeks of dietary intervention, the mice were killed, and serum and tissue samples were examined. Serum and hepatic lipid profile, insulin, leptin concentration and expression level of lipid anabolic genes like peroxisome proliferator-activated receptor γ, stearoyl-CoA desaturase-1, liver X receptor α and SREBP2 were significantly decreased (<0.05) along with body and epididymal fat pad weight in the HF-KCO group compared with the HF-KC and HF group. CONCLUSIONS: These results suggested that kimchi fermented with the starter W. koreensis OK1-6 has anti-obesity effects in HF-induced obese mice. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.

Spermidine may decrease ER stress in pancreatic beta cells and may reduce apoptosis via activating AMPK dependent autophagy pathway.

The risk for diabetes increases with increasing BMI<25. Insulin resistance is the key factor for type 2 diabetes; studies revealed that endoplasmic reticulum stress is the main factor behind this disease. With increase in ER stress, pancreatic beta cells start to undergo apoptosis, leading to a decline in the pancreatic beta cell population. The ER stress arises due to unfolded protein response. Recently, spermidine get importance for increasing the longevity in most of the eukaryotes including yeast, Caenorhabditis elegans, Drosophila and human peripheral blood mononuclear cells via induction of autophagy pathway. Autophagy is also involved in regulation of scavenging of proteins. One of the major cellular pathways for scavenging the aggregated intracellular protein is autophagy. Hence spermidine can be a candidate for the treatment type 2 diabetes. Autophagy genes are regulated by mTOR (mammalian Target Of Rapamycin) dependent or independent pathway via AMPK. Hence either inhibition of mTOR or activation of AMPK by spermidine will play two crucial roles, first being the activation of autophagy and secondly the reduction of endoplasmic reticulum stress which will reduce beta cell death by apoptosis and thus can be a novel therapeutic candidate in the treatment of insulin resistance in type 2 diabetes and preserving pancreatic beta cell mass.