Insulin resistance is improved in high-fat fed mice by photobiomodulation therapy at 630 nm.

Photobiomodulation therapy (PBMT) in the infrared spectrum exerts positive effects on glucose metabolism, but the use of PBMT at the red spectrum has not been assessed. Male Swiss albino mice were divided into low-fat control and high-fat diet (HFD) for 12 weeks and were treated with red (630 nm) PBMT or no treatment (Sham) during weeks 9 to 12. PBMT was delivered at 31.19 J/cm2 , 60 J total dose per day for 20 days. In HFD-fed mice, PBMT improved glucose tolerance, insulin resistance and fasting hyperinsulinemia. PBMT also reduced adiposity and inflammatory infiltrate in adipose tissue. Phosphorylation of Akt in epididymal adipose tissue and rectus femoralis muscle was improved by PBMT. In epididymal fat PBMT reversed the reduced phosphorylation of AS160 and the reduced Glut4 content. In addition, PBMT reversed the alterations caused by HFD in rectus femoralis muscle on proteins involved in mitochondrial dynamics and ß-oxidation. In conclusion, PBMT at red spectrum improved insulin resistance and glucose metabolism in HFD-fed mice.

Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury.

BACKGROUND AND AIMS: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. CONCLUSION: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS.

Molecular mechanisms involved in the angiotensin-(1-7)/Mas signaling pathway in cardiomyocytes.

Recently there has been growing evidence suggesting that beneficial effects of angiotensin-(1-7) [Ang-(1-7)] in the heart are mediated by its receptor Mas. However, the signaling pathways involved in these effects in cardiomyocytes are unknown. Here, we investigated the involvement of the Ang-(1-7)/Mas axis in NO generation and Ca(2+) handling in adult ventricular myocytes using a combination of molecular biology, intracellular Ca(2+) imaging, and confocal microscopy. Acute Ang-(1-7) treatment (10 nmol/L) leads to NO production and activates endothelial NO synthase and Akt in cardiomyocytes. Ang-(1-7)-dependent NO raise was abolished by pretreatment with A-779 (1 micromol/L). To confirm that Ang-(1-7) action is mediated by Mas, we used cardiomyocytes isolated from Mas-deficient mice. In Mas-deficient cardiomyocytes, Ang-(1-7) failed to increase NO levels. Moreover, Mas-ablation was accompanied by significant alterations in the proteins involved in the regulation of endothelial NO synthase activity, indicating that endothelial NO synthase and its binding partners are important effectors of the Mas-mediated pathway in cardiomyocytes. We then investigated the role of the Ang-(1-7)/Mas axis on Ca(2+) signaling. Cardiomyocytes treated with 10 nmol/L of Ang-(1-7) did not show changes in Ca(2+)-transient parameters such as peak Ca(2+) transients and kinetics of decay. Nevertheless, cardiomyocytes from Mas-deficient mice presented reduced peak and slower [Ca(2+)](i) transients when compared with wild-type cardiomyocytes. Lower Ca(2+) ATPase of the sarcoplasmic reticulum expression levels accompanied the reduced Ca(2+) transient in Mas-deficient cardiomyocytes. Therefore, chronic Mas-deficiency leads to impaired Ca(2+) handling in cardiomyocytes. Collectively, these observations reveal a key role for the Ang-(1-7)/Mas axis as a modulator of cardiomyocyte function.