Myocardial function during chronic food restriction in isolated hypertrophied cardiac muscle

Background: the effect of food restriction (FR) on myocardial performance has been studied in normal hearts. Few experiments analyzed the effects of undernutrition on hearts subjected to cardiac overload. The aim of this study was to determine whether chronic FR promotes more significant changes in hypertrophied hearts than in normal hearts. Methods: Myocardial performance was studied in isolated left ventricular papillary muscle from young male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The animals subjected to FR were fed 50% of the amount of food consumed by control groups for 60 days. Isolated muscles were studied while contracting isometrically and isotonically. Results: FR decreased the body weight and the left ventricular weight in both groups. FR increased the left ventricular weight-to-body weight ratio in the WKY rats and tended to decrease this ratio in SHR (P = 0.055). The arterial systolic pressure was greater in SHR than in WKY groups and did not change with FR. In the animals with normal diet, myocardial performance was better in SHR than in WKY. FR increased time to tension to fall from peak to 50% of peak tension and time to peak tension in the WKY rats and time to peak tension in the SHR. Conclusions: FR for 60 days has a trend to attenuate the development of cardiac hypertrophy and does not promote more mechanical functional changes in the hypertrophied myocardium than in the normal cardiac muscle.

Food restriction-induced myocardial dysfunction demonstrated by the combination of in vivo and in vitro studies

The aim of this study was to test the hypothesis that protein-calorie undernutrition decreases myocardial contractility jeopardizing ventricular function, and that ventricular dysfunction can be detected noninvasively. Five-month-old male Wistar-Kyoto rats were fed with regular rat chow ad libitum for 90 days (Control group, n = 14). A second group of rats received 50% of the amount of diet consumed by de control group (Food restricted group, n = 14). Global LV systolic function was evaluated in vivo, noninvasively, by transthoracic echocardiogram. After echocardiographic study, myocardial contractility was assessed in vitro in the isovolumetrically beating isolated heart in eight animals from each group (Langendorff preparation). The in vivo LV fractional shortening showed that food restriction depressed LV systolic function (p < 0.05). Myocardial contractility was impaired as assessed by the maximal rate of rise of LV pressure (+dP/dt), and developed pressure at diastolic pressure of 25 mmHg (p < 0.05). Furthermore, food restriction induced eccentric ventricular remodeling, and reduced myocardial elasticity and LV compliance (p < 0.05). In conclusion, food restriction causes systolic dysfunction probably due to myocardial contractility impairment and reduction of myocardial elasticity. © 2002 Elsevier B.V. All rights reserved.

A comparative study of myocardial function and morphology during fasting/refeeding and food restriction in rats

Background: This study compared the influence of fasting/refeeding cycles and food restriction on rat myocardial performance and morphology. Methods: Sixty-day-old male Wistar rats were submitted to food ad libitum (C), 50% food restriction (R50), and fasting/refeeding cycles (RF) for 12 weeks. Myocardial function was evaluated under baseline conditions and after progressive increase in calcium and isoproterenol. Myocardium ultrastructure was examined in the papillary muscle. Results: Fasting/refeeding cycles maintained rat body weight and left ventricle weight between control and food-restricted rats. Under baseline conditions, the time to peak tension (TPT) was more prolonged in R50 than in RF and C rats. Furthermore, the maximum tension decline rate (-dT/dt) increased less in R50 than in RF with calcium elevation. While the R50 group showed focal changes in many muscle fibers, such as the disorganization or loss of myofilaments, polymorphic mitochondria with disrupted cristae, and irregular appearance or infolding of the plasma membrane, the RF rats displayed few alterations such as loss or disorganization of myofibrils. Conclusion: Food restriction promotes myocardial dysfunction, not observed in RF rats, and higher morphological damage than with fasting/refeeding. The increase in TPT may be attributed possibly to the disorganization and loss of myofibrils; however, the mechanisms responsible for the alteration in -dT/dt in R50 needs to be further clarified. © 2010 Elsevier Inc. All rights reserved.

Short periods of food restriction do not affect growth, survival or muscle development on pacu larvae

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Physiological Response to Dolops carvalhoi (Crustacea: Branchiura) Infection by Pacu, Piaractus mesopotamicus, Subjected to Short Cycles of Food Restriction and Refeeding

Feeding strategies that reduce feed and promote compensatory growth could be an interesting tool to reduce costs in the fish production. However, fish health must be monitored to evaluate if their physiological response to adverse conditions, such as parasite infection, does not become compromised. A 12-wk growth trial was conducted to determine the physiological responses of pacu, Piaractus mesopotamicus, that were subjected to different fasting/refeeding cycles and infected with the Dolops carvalhoi. The schemes were: (i) control group fish (FD), (ii) food-restricted and controlled refeeding group (FR/Rc), and (iii) food-restricted and refeeding to satiation group (FR/Rs). After 84 d, the fish were exposed to D. carvalhoi for 30 h. The fish subjected to food restriction did not exhibit compensatory growth. Cortisol levels decreased in all groups within 30 h after infection. Glucose levels increased 6 h after the D. carvalhoi in the FR/Rs and 30 h after infection in the FD. In all of the fish groups, the hematocrit values were reduced after infection, and it was associated with a reduction in the mean corpuscular volume and erythrocytes. At 30 h after infection, the number of erythroblasts increased. The use of the feeding schemes does not indicate a failure of the pacu physiological responses.

Fetal kidney programming by severe food restriction: effects on structure, hormonal receptor expression and urinary sodium excretion in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Intrauterine food restriction alters the expression of uncoupling proteins in brown adipose tissue of rat newborns

A previous study from our laboratory showed that maternal food restriction (MFR) delays thermoregulation in newborn rats. In neonates brown adipose tissue (BAT) is essential for thermogenesis due to the presence of uncoupling proteins (UCPs). The aim of this study was to evaluate the influence of MFR on the UCPs mRNA and protein expression in BAT and skeletal muscle (SM) of the newborn rat. Female Wistar EPM-1 control rats (CON) received chow ad libitum during pregnancy, whereas food-restricted dams (RES) received 50% of the amount ingested by CON. Fifteen hours after birth, the litters were weighed and sacrificed. Blood was collected for hormonal analysis. BAT and SM were used for determination of UCPs mRNA and protein expression, and Ca2+-ATPase sarcoplasmic reticulum (SERCA1). RES pups showed a significant reduction in body weight and fat content at birth. MFR caused a significant increase in the expression of UCP1 and UCP2 in BAT, without changes in UCP3 and SERCA1 expression in BAT and SM. No differences between groups were found for leptin, T4 and glucose levels. RES pups showed increased insulin and decreased T3 levels. The delay in development of thermoregulation previously described in RES animals appears not to result from impairment in thermogenesis, but from an increase in heat loss, since MFR caused low birth weight in pups, leading to greater surface/volume ratio. The higher expression of UCP1 and UCP2 in BAT suggests a compensatory mechanism to increased thermogenesis. (C) 2011 Elsevier Ltd. All rights reserved.

Feto-placental development in the rabbit is altered by maternal food restriction from early pregnancy

Feto-placental development in the rabbit is altered by maternal food restriction from early pregnancy Maternal under-nutrition can induce Intrauterine Growth Restriction by placental insufficiency. To determine the consequences in the rabbit feto-placental unit, 32 pregnant rabbits were allocated in three feeding groups: ad libitum diet (Group C; n=9); restricted to 50% of their ad libitum intake during the pre-implantational period (Day 0 to Day 7) (Group PR; n=11) or restricted from Day 0 to Day 28 (Group TR; n=12).

Influence of food restriction on the reproduction and larval performance of matrinxã, Brycon amazonicus (Spix and Agassiz, 1829)

Este estudo avaliou o efeito da restrição alimentar e realimentação na reprodução de fêmeas e no crescimento inicial e sobrevivência de larvas de matrinxã, Brycon amazonicus. Matrizes distribuídas em 8 viveiros (15 peixes/tanque) foram alimentadas diariamente (em 4 tanques - G1) e alimentados em ciclos de 3 dias de alimentação seguidos de 2 dias de restrição (em 4 tanques - G2) por 6 meses antes da desova. Na indução à desova, 57% das fêmeas no G1 e 45% no G2 desovaram. Os pesos médios dos oócitos foram 208,1 g (G1) e 131,6 g (G2), sendo os oócitos G2 menores (1,017 ± 0,003 mm) que os oócitos de G1 (1,048 ± 0,002 mm). As taxas de fertilização (71,9 ± 12,6% e 61,2 ± 13,7%) e de eclosão (61,3 ± 33,9% e 67,5 ± 23,4%) entre os G1 e G2 não diferiram. Larvas foram coletadas na eclosão e às 24, 48 e 72 horas de incubação para medida do crescimento e as restantes transferidas para aquários e amostradas 1, 5, 9 e 15 dias depois. Na transferência, as larvas G1 e G2 tinham pesos similares (1,5 ± 0,15 e 1,46 ± 0,07 mg), mas o comprimento das larvas G2 era maior (6,2 ± 0,13 e 6,7 ± 0,14 mm). Ao 9° dia, quando é recomendada a transferência dos juvenis para tanques externos, os juvenis G2 tinham peso (13,6 ± 0,26 e 18,9 ± 0,07 mg) e comprimento (11,8 ± 0,09 e 14,5 ± 0,04 mm) maiores, mas no 15º dia os juvenis G1 eram maiores em peso (90,2 ± 1,19 e 68,6 ± 0,77 mg) e comprimento (18,8 ± 0,16 e 18,5 ± 0,04 mm). Aos 15 dias, a prole das fêmeas submetidas à restrição alimentar apresentou sobrevivência mais alta que a prole das fêmeas alimentadas diariamente (24,7 ± 2,07% e 19,2 ± 1,91%). A restrição alimentar imposta às fêmeas de matrinxã, apesar de reduzir o número de fêmeas que desovaram e a quantidade de oócitos extrusados, não afetou a fertilização e eclosão das larvas e melhorou a sobrevivência final das larvas.

Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance

Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance. (C) 2011 Elsevier Inc. All rights reserved.

Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in severely food-restricted rats

We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2), phospholamban (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 +/- 0.48 vs food-restricted group = 4.84 +/- 0.33, P < 0.01). The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 +/- 0.44 vs food-restricted group = 7.96 +/- 0.45, and control = 1.52 +/- 0.06 vs food-restricted group = 1.53 +/- 0.10, respectively). Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release.

Mechanical, biochemical, and morphological changes in the heart from chronic food-restricted rats

Food restriction (FR) has been shown to induce important morphological changes in rat myocardium. However, its influence on myocardial performance is not completely defined. We examined the effects of chronic FR on cardiac muscle function and morphology. Sixty-day-old Wistar-Kyoto rats were fed a control (C) or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Fragments of the LV free wall were analysed by light microscopy, and the ultrastructure of the myocardium was examined in the LV papillary muscle. The myocardial collagen concentration was also evaluated. FR decreased body weight (BW) and LV weight (LVW); the LVW/BW ratio was higher in the restricted group (C, 1.86 +/- 0.17 mg/g; FR, 2.19 +/- 0.31 mg/g; p < 0.01). In the FR animals, the cardiac fibers were polymorphic, some of them were of small diameter and others presented lateral infoldings; the ultrastructural alterations were focal and included reduction of sarcoplasmic content, absence and (or) disorganization of myofilaments and Z line, numerous electron dense and polymorphic mitochondria, and deep infoldings of the plasma membrane. The hydroxyproline concentration was higher in the FR animals (p < 0.01). FR prolonged the contraction and relaxation time of the papillary muscle and did not change its ability to contract and shorten. In conclusion, although a 90-day period of FR caused striking myocardial ultrastructural alterations and increased the collagen concentration, it only minimally affected the mechanical function.