The expression of orexigenic and anorexigenic factors in middle‐aged female rats that had been subjected to prenatal undernutrition

Abstract

Fetal growth retardation, which affects short- and long-term fetal brain development, is associated with metabolic, hematological, and thermal disturbances, which can increase the risk of metabolic syndrome later in life. Orexigenic and anorexigenic factors regulate food intake and energy expenditure. We studied how the expression of these factors was affected by food deprivation (FD) in middle-aged female rats that had been subjected to prenatal undernutrition. Eight pregnant rats were divided into two groups, the normal nutrition (NN) (n=4) group and the undernutrition (UN) (n=4) group, which received 50% (approximately 11 g) of the daily food intake of the normal nutrition rats from day 13 of pregnancy to delivery. The pups from these dams were defined as the maternal NN (mNN) and maternal UN (mUN) groups, respectively. After weaning, all of the pups were housed and allowed ad libitum access to food and water. At the age of 6 months, both groups of pups were sub-divided into three groups. One group was allowed to consume normal amounts of food (Fed), and the other two groups were subjected to 24h or 48 h FD (n=7-8 per group). The rats' serum leptin levels and hypothalamic mRNA expression levels of various orexigenic or anorexigenic factors were measured. In both the mNN and mUN rats, the serum leptin levels of the 24h and 48 h FD groups tended to be lower than those of the Fed group, and the serum leptin levels of the 24h FD mUN rats and the Fed mUN rats differed significantly. The hypothalamic neuropeptide Y (NPY) mRNA expression levels of the 24h and 48 h FD groups were significantly higher in the mUN rats than in the mNN rats. In addition, among the mUN rats the hypothalamic NPY mRNA expression levels of the 48 h FD group were significantly higher than those of the Fed group. In both the mNN and mUN rats, prepro-orexin mRNA expression was lower in the 48 h FD group than in the corresponding Fed group. Among the mUN rats, the 48 h FD group exhibited significantly lower hypothalamic proopiomelanocortin (POMC) mRNA expression than the Fed group, and a similar tendency was seen among the mNN rats. Among the mNN rats, the 24h FD group displayed significantly higher hypothalamic leptin receptor (OBRb) mRNA levels than the Fed group. However, no such differences were seen among the mUN rats. As a result, the hypothalamic OBRb mRNA expression levels of the mUN rats in the 24h and 48 h FD groups were lower than those of the corresponding mNN rat groups. These findings indicate that rats that are subjected to prenatal undernutrition exhibit upregulated expression of orexigenic factors and are more sensitive to FD in middle age, which might increase their risk of developing metabolic disorders in later life.

A proteomics–metabolomics approach indicates changes in hypothalamic glutamate–GABA metabolism of adult female rats submitted to intrauterine growth restriction

“…The existence of a relationship between low birth weight and the development of metabolic disturbances in adulthood has been established. In agreement with ours [17, 19, 25] and other reports [26, 27] in both genders, here we observed that 50% calorie restriction throughout pregnancy induced low birth weight of the female offspring. At adulthood, these restricted females had normal body weight but increased body fat, in accordance with earlier data [9, 28].…”

Prenatal undernutrition disrupted the sexual maturation, but not the sexual behavior, in male rats

“…All the pregnant rats were divided into a maternal normal nutrition (mNN) group and a maternal undernutrition (mUN) group. The mUN mothers received 50% of the amount of the daily food intake of the mNN mothers from gestation day 13‐21 . After birth, the mothers were allowed ad libitum access to water and food during the lactation period.…”

“…The mUN mothers received 50% of the amount of the daily food intake of the mNN mothers from gestation day 13-21. 7 After birth, the mothers were allowed ad libitum access to water and food during the lactation period. The body weight of the pregnant rats and pups was measured from gestation days 14-21 and from postnatal day (PND) 1 to PND 35, respectively.…”

“…2,3 It also has been reported that prenatal undernutrition has impaired the onset of puberty and the estrous cycle in male and female rats [4][5][6] and has induced metabolic disorders. 7,8 Furthermore, the exposure to lipopolysaccharide (LPS) in the early neonatal period has delayed vaginal opening and preputial separation (PS) and disrupted sexual behavior in male and female rats. 9,10 However, it has been poorly investigated whether prenatal undernutrition influence sexual behavior or not.…”

The reduction in sexual behavior induced by neonatal immune stress is not related to androgen levels in male rats

“…In addition, maternal psychological stress in the prenatal period was found to be associated with lower cognitive and linguistic abilities in children aged five and a half years (Laplante et al, 2008). In rats, undernutrition in the prenatal period was demonstrated to be associated with an increased risk of type 2 diabetes (Park et al, 2008) and enhanced hypothalamic mRNA expression of the orexigenic peptide neuropeptide Y (Tungalagsuvd et al, 2016) in late adulthood. Furthermore, immune stress in the early neonatal period enhanced the activity of the hypothalamic‐pituitary‐adrenal (HPA) axis, increased the incidence of tumor metastasis, and caused body weight to rise in adulthood (Shanks et al, 1995, 2000; Hodgson et al, 2001; Boisse et al, 2004; Ellis et al, 2005).…”