ABC | Volume 111, Nº3, September 2018

Original Article Pinotti et al Fasting/refeeding cycles and myocardial remodeling Arq Bras Cardiol. 2018; 111(3):400-409 Figure 4 – Ultrastructural study of LV papillary muscle (n = 3 per group). Photographs A and B correspond to the control group, photographs C, D and E to the food‑restriction (R 50 ) group and photographs F and G to the refeeding group (RF) group. The control group showed preserved ultrastructure with normal myofibrils (M), sarcoplasmic reticulum (arrowhead), mitochondria (mi), nuclear membrane (N) and plasma membrane (arrow). Food restriction rats showed cellular changes, including polymorphic mitochondria (*), myofibril disorganization (**), and infolding of the plasma membrane (arrow). The papillary muscle during refeeding showed preserved myofibrils (M), mitochondria (mi), and plasma membranes (arrow), polymorphic mitochondria (*) and capillary (C). Source: Research team. cytosolic Ca 2+ , and β -adrenergic system. Nevertheless, the lower response of food restricted rats to the increase of extracellular Ca 2+ concentration can be related to changes in the general mechanisms involved in Ca 2+ cycling such as sarcolemmal Na + /Ca 2+ exchanger, sarcolemmal L-type channel, sarcoplasmic reticulum (SR), ryanodine receptor, SR Ca 2+ uptake pump, and the myofilament Ca 2+ sensitivity. 35 In relation to RF, this process may be faster and more balanced, but no study was found to support this statement and show the activity and protein expression of Ca 2+ handling regulatory proteins. Another explanation could be related to the role of cytokine in intermittent fasting mediated cardioprotection. The influx of inflammatory cells and production of pro‑inflammatory mediators contribute to myocardial injury. 36 Nevertheless, adiponectin can protect myocardial cells against ischemic injury by activating the cyclic AMP-dependent protein kinase - Akt pathway, being the latter mediated, in part, by caloric restriction. 37 Thus, the beneficial effects of fasting/refeeding may function through anti-inflammatory cytokine pathways. Few studies have evaluated the β -adrenergic components in experimental models of fasting/refeeding. 25,35 Some studies have shown that cardiac function impairment is related to β -adrenergic system changes, 35 while other researchers have not reported reduced β -adrenergic response. 25 The literature shows that a decrease in cardiac β -receptor number has been reported in several hypertensive models known to be associated with an increase in sympathetic nerve activity, including SHR. 38 Thus, the association between increased sympathetic activity and cardiac β -receptor downregulation is sufficiently close to suggest that the finding of decreased β -receptor number after starvation and refeeding is indicative of persistently elevated cardiac sympathetic drive. However, in the current study, there is no damage of β -system in the RF rats, since the cardiac function was similar to that of the C group. The present data tend to support the hypothesis that isoproterenol stimulation reveals that the β -adrenergic system and cAMP phosphorylation of proteins related to Ca 2+ handling were preserved in refeeding rats. Thus, fasting/refeeding cycles have become the subject of considerable scientific interest as a potential dietary approach for weight-loss and improving cardiometabolic health. 406