Influence of intake of different types of fatty acids during pregnancy and lactation in obese rats on epigenetics and energy homeostasis regulation of offspring after lactation

• Grant number: 21/10375-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2023
• Effective date (End): February 29, 2024
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Luciana Pellegrini Pisani
• Grantee: Esther Alves de Souza
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

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. of life. 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; global DNA methylation and HDAC enzyme activity in the hypothalamus; protein expression of DNMTs, HDAC11, SIRT-1, insulin, leptin and adiponectin receptors, AMPK, PGC-1, NF-kB in the hypothalamus; miRNA-204 expression 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.