Obesity has become a threat to global metabolic health. Obesity rates have risen to 511 million people with a body mass index (BMI) > 30 in 2010 and are estimated to rise to 1 billion people by 2030. The Obesity Federation has developed a disability-adjusted life years (DALYs) index, which measures the number of years lost due to premature mortality and/or ill-health. One-fifth of DALYs can be attributed to high BMI, indicating that obesity is the leading factor in most non-communicable diseases (“World Obesity Atlas, 2022,” 2022). Obesity induces a pro-inflammatory environment that can cause a condition known as “leaky gut”, which in turn results in an increase in the passage of inflammatory substances into the bloodstream, leading to direct pro-inflammatory effects on the whole organism (Kobayashi et al., 2022; Martín-Mateos and Albillos, 2021). Furthermore, parental obesity predisposes offspring to several changes that affect metabolism and function of various systems throughout life. The aim of this work was to study whether the fetuses and offspring of overweight rats display intestinal anomalies related to intestinal inflammatory conditions. Furthermore, since this offspring develops fatty liver (Heinecke et al., 2020; Mazzucco et al., 2016), we aimed to study whether intestinal impairments induced by maternal metabolic programming lead to abnormalities in incretin and glucose homeostasis that may aggravate the liver pathology.

The intestine has many essential functions, including absorption and transport of nutrients into the portal circulation, excretion of metabolic-waste substances into the luminal compartment, maintenance of the immune barrier, interaction with the luminal microbiota and enteroendocrine function (Abdalqadir and Adeli, 2022; Chen et al., 2021; Gribble and Reimann, 2019). Enteroendocrine cells produce and secrete incretins into the bloodstream in response to the uptake of glucose, amino acids and lipids. Incretins, such as glucose-insulinotropic releasing peptide (GIP) and glucagon-like derived peptide 1 (GLP1), are small peptides secreted into the circulation that have an insulinotropic function. They induce insulin secretion and synthesis, preparing the body for the metabolic challenge of nutrients (Gribble and Reimann, 2019; Ko et al., 2020). Both incretins are translated as a primary transcript, pro-gip and pre-pro-glucagon (gcg) and then translated and post-translationally processed into GIP or GLP1, GLP2 and other peptides (Chiang et al., 2012; Holst, 2009; Martínez-Rodríguez and Gil, 2012). GLP2 lacks insulinotropic function but has been identified as the most important intestinotrophic peptide, because of its ability to stimulate the mucus production and to promote barrier function (Abdalqadir and Adeli, 2022).

During intrauterine and early postnatal life, individuals are exposed to the maternal environment. Maternal metabolic state, nutrition, inflammation and stressors such as contaminants or pathological and non-pathological microbiota modify the metabolic program that the organism will follow from that time on (Chen and Gur, 2019; Fernandez-Twinn et al., 2019; Gómez-Roig et al., 2021; Lindsay et al., 2019; Picó et al., 2021). During this stage of development, the epigenetic marks of the fetus/neonate are erased and re-established, creating an opportunity for the environment to modify the epigenome. The intestinal function of a developing individual is strongly dependent on the maternal nutrition, metabolic condition and microbiome. Offspring from women with obesity and animal models of obesity exhibit intestinal inflammation, increased permeability, and vulnerability to inflammatory-related intestinal pathologies (Castro-Rodríguez et al., 2021; Gruber et al., 2015; Słupecka-Ziemilska et al., 2021; Yan et al., 2011; Zhu et al., 2010). This work studies the intestinal impairments in the offspring from rats with overweight.