Long-term effects of early overfeeding and food restriction during puberty on cardiac remodeling in adult rats

Abstract

Nutritional disorders during the perinatal period cause cardiometabolic dysfunction, which is observable in the early overfeeding (EO) experimental model. Therefore, severe caloric restriction has the potential of affecting homeostasis through the same epigenetic mechanisms, and its effects need elucidation. This work aims to determine the impact of food restriction (FR) during puberty in early overfed obese and non-obese animals in adult life. Three days after delivery (PN3), Wistar rats were separated into two groups: normal litter (NL; 9 pups) and small litter (SL; 3 pups). At PN30, some offspring were subjected to FR (50%) until PN60, or maintained with free access to standard chow. NL and SL animals submitted to food restriction (NLFR and SLFR groups) were kept in recovery with free access to standard chow from PN60 until PN120. Body weight and food intake were monitored throughout the experimental period. At PN120 cardiovascular parameters were analyzed and the animals were euthanized for sample collection. SLNF and SLFR offspring were overweight and had increased adiposity. Differences in blood pressure were observed only between obese and non-obese animals. Obese and FR animals have cardiac remodeling showing cardiomyocyte hypertrophy and the presence of interstitial and perivascular fibrosis. FR animals also show increased expression of AT1 and AT2 receptors and of total ERK and p-ERK. The present study showed that EO leads to the obese phenotype and cardiovascular disruptions. Interestingly, we demonstrated that severe FR during puberty leads to cardiac remodeling.

Angiotensin-(1-7) Treatment Early in Life Prevents Cardiac Hypertrophy in Adult Hypertensive Rats

“…The intense gene transcription and protein translation in this phase results in a particular susceptibility to epigenetic modifications, leading to the later development of cardiovascular diseases. 12,13 We have previously reported that 30-day-old rats submitted to food restriction presented cardiomyocyte hypertrophy and interstitial and perivascular fibrosis accompanied by higher expression of both AT1 and AT2 receptors, 19 suggesting that the RAS may participate in pathological cardiac adjustments within the puberty programming window. In addition, our group previously showed that the treatment with Ang-(1-7) during the gestational period was able to attenuate the increase of blood pressure in the adult offspring of SHR.…”

“…16,17 Our group has previously shown that the treatment with an ACE2 activator (diminazene aceturate) or Ang-(1-7) during the gestational period of pregnant spontaneously hypertensive rats (SHRs) attenuated the development of hypertension and cardiac remodeling in the adult offspring. 18 We have reported that young rats (30-day-old) submitted to food restriction developed cardiac remodeling and increased the cardiac expression of AT1 and AT2 receptors, 19 suggesting that the RAS may participate in pathological cardiac adjustments within the prepuberty programming window. Therefore, there is no evidence that the treatment with Ang-(1-7) in the prepuberty can promote cardioprotection in adulthood.…”

“…We have reported that young rats (30-day-old) submitted to food restriction developed cardiac remodeling and increased the cardiac expression of AT1 and AT2 receptors, 19 suggesting that the RAS may participate in pathological cardiac adjustments within the prepuberty programming window. Therefore, there is no evidence that the treatment with Ang-(1-7) in the prepuberty can promote cardioprotection in adulthood.…”

Puberty as a DOHaD programming window: high-fat diet induces long-term hepatic dysfunction in male rats

“…3 Nutritional disorders, such as overnutrition or undernutrition during phenotypic plasticity periods program to obesity, diabetes, and cardiovascular disorders. [4][5][6] Epidemiological and experimental studies have demonstrated that a high-fat (HF) diet induces overweight/obesity, hyperphagia, insulin resistance, glucose intolerance, hepatic dysfunctions, and other disturbances. [7][8][9][10] Specifically, HF intake during the puberty induces abnormalities in reproductive function, adiposity, and impairment of hippocampal-dependent memory associated with enhanced hippocampal inflammation later in life in male rats.…”