Maternal transfer of antibodies and BAT development

• Grant number: 23/05350-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2023
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Luiz Osório Silveira Leiria
• Grantee: Paulo Henrique de Melo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Heat generation in response to environmental stimuli, such as cold and diet is called adaptative thermogenesis. Brown adipose tissue (BAT) is the specialized tissue responsible for it and due to its high capacity to catabolize energy substrates, it becomes central to energy homeostasis. BAT is a complex tissue, which has numerous brown adipocytes associated with blood vessels, nerve fibers, progenitor and immune cells. It is known that intercellular communication in the BAT niche is crucial for the function and development of this tissue. Recently it has been demonstrated that IL-17C+ Tgd cells, regulatory T cells and M2 macrophages have a pro thermogenic functions. Previous data from our group demonstrate a great pool of B cells in the BAT of mice, however the role of these cells in this context had not yet been explored. We observed that mice deficient in mature B cells (muMt-/-) have lower BAT mass and whitening since the neonatal age, culminating in a marked failure in adaptive thermogenesis in the adulthood. Previously, we had used animals were generated from breeding between deficient or wild-type homozygotes, however, we decided to improve our breeding strategies to obtain littermates mice by breeding heterozygotes mice (which the mother transfers antibodies to the offspring). Interestingly, the offspring of MuMt-/- and WT mice generated by heterozygotes breeding did not show differences when submitted to the cold challenge and the glucose tolerance test. This raised some questions about how the breed strategy could interfere with the results obtained in the offspring. The literature shows that the transfer of maternal antibodies affects the composition of the microbiota and the immune system of the offspring, while other works demonstrate that the microbiota is critical for the thermogenic and metabolic functions. Therefore, we hypothesize that the transfer of maternal antibodies is the key process that determines the metabolic differences observed among the evaluated mice, placing the microbiota as an intermediary of this phenotype. For this, we will establish new breeding from which deficient or wild-type mice will receive or not maternal antibodies. Subsequently, all animals generated from these different breeding will be evaluated according to metabolic, thermogenic, immunological and microbiota composition parameters. In addition, microbiota transfer will be performed between mice that received or not maternal antibodies and thermogenic and metabolic parameters will be evaluated. Thus, this work aims to unravel the metabolic and thermogenic processes that can be controlled by the transfer of maternal antibodies.