Maternal food restriction in rats of the F0 generation increases retroperitoneal fat, the number and size of adipocytes and induces periventricular astrogliosis in female F1 and male F2 generations

Abstract

The present study investigated whether male offspring (F generation) from female rats (F generation) whose mothers (F generation) were food restricted during gestation inherit a phenotypic transgenerational tendency towards being overweight and obese in the juvenile period, in the absence of food restriction in the F/F generations. Dams of the F generation were 40% food restricted during pregnancy. Bodyweight, the number and size of larger and small hypodermal adipocytes (HAs), total retroperitoneal fat (RPF) weight and the expression of glial fibrillary acidic protein (GFAP) in periventricular hypothalamic astrocytes (PHAs), as determined by immunohistochemistry, were evaluated in both generations. In the female F generation, there was low bodyweight gain only during the juvenile period (30-65 days of age), a decrease in the size of small adipocytes, an increase in the number of small adipocytes, an increase in RPF weight and an increase in GFAP expression in PHAs at 90-95 days of age. In males of the F generation at 50 days of age, there was increased bodyweight and RPF weight, and a small number of adipocytes and GFAP expression in PHAs. These data indicate that the phenotypic transgenerational tendency towards being overweight and obese was observed in females (F) from mothers (F) that were prenatally food restricted was transmitted to their male offspring.

Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure

“…Additionally, while the F1 generation trended toward lower BMIs early in development, the F2 generation had higher BMI scores. In other studies considering underweight mothers and the weight gain of their offspring, maternal undernutrition improves the metabolic health of the next generation 52 and can lead to weight gain and obesity in the next generation 53 , much like what we observed in our overweight F2 generation compared to their underweight F1 mothers.…”

Food deprivation in F0 generation and hypercaloric diet in F1 generation reduce F2 generation astrogliosis in several brain areas after immune challenge

“…Furthermore, half of rats of F2 generation received an immune challenge with LPS, a non‐replicating component of the cell walls of Gram‐negative bacteria, to observe the grade of neuroinflammation. Overweight/obesity increases the expression of the GFAP, inducing astrogliosis, a defensive transformation in response to injury and inflammation as previously observed in the hypothalamus by Joaquim et al (2016a,b).…”

“…Previously, our group showed a transgenerational tendency to obesity/overweight in male offspring (F2 generation) from female rats (F1 generation) whose mothers (F0 generation) were food restricted during gestation in the absence of food restriction in the F1/F2 generations (Joaquim et al, 2016a,b). Presently, no differences were observed in the BW between F2NDS and F2HDS on PND50.…”

Animal Foetal Models of Obesity and Diabetes – From Laboratory to Clinical Settings

“…In rats both paradigms of maternal malnutrition (regardless of the timeframe of undernutrition, whether energy restriction lasted throughout gestation or only part of this period) often resulted in a lower birth weight (up to ~40%) (124)(125)(126)(127). However, most of these studies showed that despite the lower birth weight observed in the offspring, these animals were often characterised by increased adiposity, gain of the adipose tissue or adipocyte size at later stages of life (124,128,129). Few studies showed that a lower body weight could persist for several days, weeks (126,127,130) or even for up to ten months, especially when the dam's age was taken into consideration, as Ware et al (131) observed.…”