Cardioprotective Signature of Short-Term Caloric Restriction

Abstract

ObjectiveTo understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR).BackgroundLifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we reveal the pathways that are modulated by short-term CR, which are associated with protection of the mouse heart from ischemia.MethodsMale 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food for 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. At d8, the left ventricles (LV) of AL and CR mice were collected for Western blot, mRNA and microRNA (miR) analyses to identify cardioprotective gene expression signatures. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI.ResultsThis short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). mRNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function.

Preoperative Short‐Term Calorie Restriction for Prevention of Acute Kidney Injury After Cardiac Surgery: A Randomized, Controlled, Open‐Label, Pilot Trial

“…The astonishingly potent effect of calorie restriction (CR) on AKI was confirmed by a more recent study from our group . Similar results have been reported in other models of renal injury (eg, cisplatinum‐induced AKI) and in other organ systems . Although a short‐term diet has been proven to be feasible and safe in patients undergoing living‐donor kidney transplantation, no prospective trials have been undertaken to investigate the possible impact of moderate CR as an organ‐protective measure.…”

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

“…Reports have indicated that caloric restriction (CR) attenuates the development of cardiomyopathy and decline in heart function normally associated with aging 12. Moderate CR decreases visceral fat and blood pressure and improves the lipid profile, glucose uptake, and insulin sensitivity, and hearts from CR rodents show an improved ischemic tolerance 13–16. Furthermore, CR preserves pancreatic mass and function by suppressing apoptosis in the db/db mouse,17 attenuates the development of hepatic steatosis in the db/db mice,18 and decreases adiposity in the genetically hyperphagic OLEFT model of type 2 diabetes 19.…”

Diabetic Cardiomyopathy: Current Approach and Potential Diagnostic and Therapeutic Targets

“…Since high levels of Fet A are correlated with higher levels of TLR2 expression at adipocyte level, this means that high Fet A level is related to inflammation during metabolic syndrome as manifested by TLRs activation [23]. It has been proved on experimental models that chronic FAs release stimulated TLR4 on adipocytes, leading to increased production of inflammatory adipokines, including interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), and monocyte chemoattractant protein-1 (MCP-1), consequently leading to increased monocyte accumulation, giving rise to impaired insulin sensitivity [24, 25]. Cohen et al demonstrated that TLR2/4, FFAs, and Fet A are increased during diabetic cardiomyopathy, but there is possibility to achieve a significant improvement of these biomarkers through a short period of caloric restriction, with a consequent therapeutic potential [24].…”