aternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germlin

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Costa-Junior, Jose Maria ^[1] ; Ferreira, Sandra Mara ^[1] ; Kurauti, Mirian Ayumi ^[1] ; Bernstein, Diana L. ^{[2, 3]} ; Ruano, Elena G. ^{[4, 5]} ; Kameswaran, Vasumathi ^{[2, 3]} ; Schug, Jonathan ^{[2, 3]} ; Freitas-Dias, Ricardo ^[1] ; Zoppi, Claudio C. ^[1] ; Boschero, Antonio C. ^[1] ; de Oliveira, Camila A. M. ^[6] ; Santos, Gustavo J. ^[7] ; Carneiro, Everardo M. ^[1] ; Kaestner, Klaus H. ^{[2, 3]}

Afiliação do(s) autor(es)

^[1] State Univ Campinas Unicamp, Biol Inst, Dept Struct & Funct Biol, BR-13083864 Campinas, SP - Brazil

^[2] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 - USA

^[3] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 - USA

^[4] August Pi & Sunyer Biomed Res Inst IDIBAPS, Diabet & Obes Lab, Campus Casanova, Barcelona 14308036 - Spain

^[5] Spanish Biomed Res Ctr Diabet & Associated Metab, Barcelona 14308036 - Spain

^[6] Univ Fed Sao Paulo, Dept Biosci, BR-11015020 Santos, SP - Brazil

^[7] Univ Fed Santa Catarina UFSC, Ctr Biol Sci, Dept Physiol Sci, Islet Biol & Metab Lab, BR-13083864 Florianopolis, SC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 1 JAN 2022.
• Citações Web of Science: 0

Resumo

Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease's (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally. (AU)

• Processo FAPESP: 15/12611-0 - Mecanismos moleculares envolvidos na disfunção e morte de células beta pancreáticas no Diabetes mellitus: estratégias para a inibição desses processos e para a recuperação da massa insular
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático