Crebl2 regulates cell metabolism in muscle and liver cells

We previously identified Drosophila REPTOR and REPTOR-BP as transcription factors downstream of mTORC1 that play an important role in regulating organismal metabolism. We study here the mammalian ortholog of REPTOR-BP, Crebl2. We find that Crebl2 mediates part of the transcriptional induction caused by mTORC1 inhibition. In C2C12 myoblasts, Crebl2 knockdown leads to elevated glucose uptake, elevated glycolysis as observed by lactate secretion, and elevated triglyceride biosynthesis. In Hepa1-6 hepatoma cells, Crebl2 knockdown also leads to elevated triglyceride levels. In sum, this works identifies Crebl2 as a regulator of cellular metabolism that can link nutrient sensing via mTORC1 to the metabolic response of cells.

Temperature and serine phosphorylation regulate glycerol-3-phosphate dehydrogenase in skeletal muscle of hibernating Richardson’s ground squirrels

Glycerol-3-phosphate dehydrogenase (G3PDH) bridges carbohydrate and lipid metabolism by interconverting glycerol-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). This reversible reaction converts G3P derived from triglyceride hydrolysis to DHAP that can then enter glycolysis or gluconeogenesis and, in the reverse reaction, makes G3P for use in triglyceride biosynthesis. Small hibernating mammals rely almost exclusively on triglyceride reserves as their fuel for energy production during torpor and the recovery of glycerol after lipolysis is an important source of carbohydrate over the nonfeeding winter months. G3PDH (∼37 kDa) was purified from skeletal muscle of euthermic and hibernating Richardson’s ground squirrels (Urocitellus richardsonii) using three column chromatography steps. Analysis of enzyme kinetic properties revealed that G3PDH from hibernator muscle had higher affinities for G3P and NAD at low (5 °C) assay temperature compared with high (21 or 37 °C) and a greater stability in the presence of denaturing agents (urea, guanidine hydrochloride) or high temperature (50 °C). Immunoblotting showed that hibernator muscle G3PDH had a higher phosphoserine content than the enzyme from euthermic controls and incubation studies showed that enzyme affinity for G3P changed significantly by stimulating endogenous protein kinases or phosphatases. Overall, this study suggests that the properties of ground squirrel muscle G3PDH are modulated by temperature and post-translational phosphorylation to alter enzyme function under euthermic versus hibernating states.

Polyphenols: Potential Use in the Prevention and Treatment of Cardiovascular Diseases

Background: Polyphenols are bioactive compounds that can be found mostly in foods like fruits, cereals, vegetables, dry legumes, chocolate and beverages such as coffee, tea and wine. They are extensively used in the prevention and treatment of cardiovascular disease (CVD) providing protection against many chronic illnesses. Their effects on human health depend on the amount consumed and on their bioavailability. Many studies have demonstrated that polyphenols have also good effects on the vascular system by lowering blood pressure, improving endothelial function, increasing antioxidant defences, inhibiting platelet aggregation and low-density lipoprotein oxidation, and reducing inflammatory responses. Methods: This review is focused on some groups of polyphenols and their effects on several cardiovascular risk factors such as hypertension, oxidative stress, atherogenesis, endothelial dysfunction, carotid artery intima-media thickness, diabetes and lipid disorders. Results: It is proved that these compounds have many cardio protective functions: they alter hepatic cholesterol absorption, triglyceride biosynthesis and lipoprotein secretion, the processing of lipoproteins in plasma, and inflammation. In some cases, human long-term studies did not show conclusive results because they lacked in appropriate controls and in an undefined polyphenol dosing regimen. Conclusion: Rigorous evidence is necessary to demonstrate whether or not polyphenols beneficially impact CVD prevention and treatment.

ATRA modulates gluconeogenesis and triglyceride biosynthesis pathway of liver in elastase induced emphysematous rats

Emphysema is a chronic pulmonary disorder characterized by the destruction and enlargement of the gas exchanging units known as alveoli. Chronic inflammation is one of the critical features associated with pathogenesis of emphysema. The inflammatory mediators generated during emphysema are thought to be infiltrated into the circulatory system, leading to systemic inflammation and thus, affecting other vital organs. The potential role of ATRA, an anti-inflammatory bio-molecule, towards molecular mechanisms governing systemic inflammation due to inflammatory mediator’s overspills in emphysema is poorly understood. Therefore, the present study deals with investigating the potential effect of ATRA on physiological functions of liver tissue in an established elastase induced emphysema rat model. Three experimental groups (i.e., control, SS; emphysema, ES; and therapy, EA) were prepared. Subsequently, liver from each rat was collected for elastase activity assay, histopathology, real-time PCR based mRNA expression analyses, total lipid estimation and western blot analysis. ATRA supplementation in emphysema group decreases elastase activity. Liver histopathology photomicrographs clearly shows an increase in number of Kupffer cells in ES than SS, while, a decrease in number of Kupffer cells was found in EA. Furthermore, upon validation at mRNA and protein level, expressions of TNF-α, enzymes of gluconeogenesis and triglyceride biosynthesis pathway were significantly increased in ES while decreased in EA when compared to SS. Therapeutic supplementation of ATRA posed a beneficial effect in maintaining the normal architecture of liver tissue along with modulation of gluconeogenesis and triglyceride biosynthesis pathways.