Litter Size Reduction as a Model of Overfeeding during Lactation and Its Consequences for the Development of Metabolic Diseases in the Offspring

Abstract

Overfeeding during lactation has a deleterious impact on the baby’s health throughout life. In humans, early overnutrition has been associated with higher susceptibility to obesity and metabolic disorders in childhood and adulthood. In rodents, using a rodent litter size reduction model (small litter) to mimic early overfeeding, the same metabolic profile has been described. Therefore, the rodent small litter model is an efficient tool to investigate the adaptive mechanisms involved in obesogenesis. Besides central and metabolic dysfunctions, studies have pointed to the contribution of the endocrine system to the small litter phenotype. Hormones, especially leptin, insulin, and adrenal hormones, have been associated with satiety, glucose homeostasis, and adipogenesis, while hypothyroidism impairs energy metabolism, favoring obesity. Behavioral modifications, hepatic metabolism changes, and reproductive dysfunctions have also been reported. In this review, we update these findings, highlighting the interaction of early nutrition and the adaptive features of the endocrine system. We also report the sex-related differences and epigenetic mechanisms. This model highlights the intense plasticity during lactation triggering many adaptive responses, which are the basis of the developmental origins of health and disease (DOHaD) concept. Our review demonstrates the complexity of the adaptive mechanisms involved in the obesity phenotype promoted by early overnutrition, reinforcing the necessity of adequate nutritional habits during lactation.

From conception to recruitment: Nutritional condition of the dam dictates the likelihood of success in a temperate ungulate

“…Understanding the link between maternal effects and population dynamics is critical for the conservation and management of mule deer and other long-lived ungulates. For example, the reproductive potential of a population is not only influenced by pregnancy rate and litter size (Noyes et al, 2002;Souza et al, 2022), but also nutritional condition of the dams that influences the survival and expression of phenotypic traits in offspring. The phenotypic traits of young ungulates likely influence all aspects of life history, beyond just survival as we have demonstrated here, including susceptibility to predation (Murray, 2002) and disease (Beldomenico and Begon, 2010), and potential size and reproductive success (Keech et al, 2000;Freeman et al, 2013) as an adult.…”

Fish oil supplementation in obese rats ameliorates metabolic syndrome response

“…Appropriate animal models, particularly those with dietary intervention, have been used to investigate early obesity and its effects in human adult life ( 3 ). An interesting obesity model whose diet is not changed is the rodent litter size reduction in early life ( 4 ). In short, at 3-4 days after birth, the litter is reduced to 3 pups per dam, but the control litter is kept with 10 or more pups per dam ( 5 ).…”

Postnatal Overfeeding in Rodents Induces a Neurodevelopment Delay and Anxious-like Behaviour Accompanied by Sex- and Brain-Region-Specific Synaptic and Metabolic Changes

“…Besides genetic factors, non-genetic factors may also evoke structural and functional changes in neuronal activity and metabolism, with impacts on neurodevelopment and behaviour throughout life [ 1 , 2 ]. Overfeeding is often a consequence of maternal obesity and the consumption of unbalanced diets is one of the factors that can contribute to disturbances in neuronal circuits during early life, namely the proper communication between central and peripheral structures [ 3 , 4 , 5 ]. Neonatal overfeeding models have been studied as representative of childhood obesity.…”

“…Neonatal overfeeding models have been studied as representative of childhood obesity. In the small litter model, both male and female pups are raised with greater access to their mother’s milk and, as a consequence, have higher susceptibility to the onset of metabolic diseases such as adiposity, insulin resistance, obesity, and type 2 diabetes, featuring a metabolic syndrome phenotype [ 3 , 6 , 7 ]. Besides these consequences, postnatal overfeeding may also contribute to reshaping neuronal connections and increase the susceptibility to behavioural alterations such as anxiety, deficits in sociability, memory, and learning impairments [ 8 , 9 ].…”