Effect of maternal hyperlipidic diet on male and female offspring health focussed on epigenetic biomarkers and energetic homeostasis

• Grant number: 22/05529-9
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2023 - January 31, 2025
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Luciana Pellegrini Pisani
• Grantee: Luciana Pellegrini Pisani
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Debora Estadella

Abstract

The period of gestation and lactation is crucial for fetal and neonatal development. The maternal diet during this period has a direct influence on the development and health of offspring with different responses between males and females. The high-fat maternal diet (HF) can cause resistance to the action of hormones such as leptin, insulin, and adiponectin, possibly associated with the inflammatory process, affecting lipid and glucose metabolism, intestinal permeability, and the hypothalamic function of the offspring, which may alter the methylation pattern of the offspring. DNA and miRNA expression, culminating in the development of obesity associated with metabolic syndrome. Hypothalamic inflammation can occur through activation of the NF-kB pathway. This can be inhibited by AMPK, a protein that also participates in several cellular functions, being able to regulate POMC and NPY-AgRP, thus maintaining energy homeostasis. The maternal diet based on SGA may have negative repercussions on fetal development and metabolism. In contrast, the maternal diet based on PUFA-n3 can improve the parameters of the offspring impaired by the maternal high-fat diet based on saturated fat. The project aims to evaluate the effect of maternal high fat diet in preconception and normolipidic rats with different types of fatty acids during pregnancy and lactation regarding inflammatory, epigenetic, and energy regulation parameters of male and female offspring at 21 days. It will be evaluated in male and female offspring: the weight and length gain delta; relative weight of hypothalamus and colon; carcass protein and fat content; fat acid profile in serum and hypothalamus; global DNA methylation and HDAC enzyme activity in the hypothalamus; miRNA-204 expression; protein expression of DNMTs, HDAC11, SIRT-1, insulin, leptin and adiponectin receptors, AMPK, PGC-1, NF-kB in the hypothalamus; inflammatory cytokine content in the hypothalamus and colon; gene and protein expression of tight junctions in the colon; POMC, NPY, PYY, and GLP-1 gene expression in the hypothalamus; serum concentration of insulin, leptin, LPS, PYY, and NPY. It is expected to understand mechanisms associated with changes in energy homeostasis according to sex and to contribute to the expansion of the study of the systems involved in the programming of fetal development. It is believed that we will be able to contribute to the understanding of the mechanisms associated with obesity, suggesting effective interventions for the prevention and control of chronic diseases. (AU)