Kinin B1 receptor controls maternal adiponectin levels and influences offspring weight gain
Thaís Alves-Silva,
Talita G.R. Húngaro,
Leandro C. Freitas-Lima,
Gabriel de Melo Arthur,
Adriano C. Arruda,
Raisa B. Santos,
Lila M. Oyama,
Marcelo A.S. Mori,
Michael Bader,
Ronaldo C. Araujo
Affiliations
Thaís Alves-Silva
Laboratory of Genetics and Exercise Metabolism, Molecular Biology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil; Max-Delbrück Center for Molecular Medicine (MDC), Campus Berlin-Buch, 13125 Berlin, Germany
Talita G.R. Húngaro
Laboratory of Genetics and Exercise Metabolism, Nephrology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil
Leandro C. Freitas-Lima
Laboratory of Genetics and Exercise Metabolism, Molecular Biology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil
Gabriel de Melo Arthur
Laboratory of Genetics and Exercise Metabolism, Molecular Biology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil
Adriano C. Arruda
Laboratory of Genetics and Exercise Metabolism, Nephrology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil
Raisa B. Santos
Laboratory of Genetics and Exercise Metabolism, Nephrology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil
Lila M. Oyama
Laboratory of Nutrition and Endocrine Physiology, Physiology Department, Federal University of São Paulo (UNIFESP), São Paulo 04023-901, Brazil
Marcelo A.S. Mori
Laboratory of Aging Biology, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), São Paulo 13083-862, Brazil
Michael Bader
Max-Delbrück Center for Molecular Medicine (MDC), Campus Berlin-Buch, 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany; Institute for Biology, University of Lübeck, Lübeck, Germany; Charité University Medicine Berlin, Berlin, Germany
Ronaldo C. Araujo
Laboratory of Genetics and Exercise Metabolism, Molecular Biology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil; Laboratory of Genetics and Exercise Metabolism, Nephrology Program, Biophysics Department, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil; Corresponding author
Summary: Given the importance of the kinin B1 receptor in insulin and leptin hormonal regulation, which in turn is crucial in maternal adaptations to ensure nutrient supply to the fetus, we investigated the role of this receptor in maternal metabolism and fetoplacental development. Wild-type and kinin B1 receptor-deficient (B1KO) female mice were mated with male mice of the opposite genotype. Consequently, the entire litter was heterozygous for kinin B1 receptor, ensuring that there would be no influence of offspring genotype on the maternal phenotype. Maternal kinin B1 receptor blockade reduces adiponectin secretion by adipose tissue ex vivo, consistent with lower adiponectin levels in pregnant B1KO mice. Furthermore, fasting insulinemia also increased, which was associated with placental insulin resistance, reduced placental glycogen accumulation, and heavier offspring. Therefore, we propose the combination of chronic hyperinsulinemia and reduced adiponectin secretion in B1KO female mice create a maternal obesogenic environment that results in heavier pups.
