Maternal high-fat diet stimulates proinflammatory pathway and increases the expression of Tryptophan Hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF) in adolescent mice hippocampus

Autor(es)

Dias, Clarissa Tavares ^[1] ; Curi, Haidar Tafner ^[1] ; Payolla, Tanyara Baliani ^[2] ; Lemes, Simone Ferreira ^[2] ; Betim Pavan, Isadora Carolina ^[3] ; Torsoni, Marcio Alberto ^[2] ; Simabuco, Fernando Moreira ^[3] ; Lambertucci, Rafael Herling ^[1] ; da Silva, Cristiano Mendes ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Lab Neurosci & Nutr, Dept Biosci, UNIFESP, Campus Baixada Santista, Santos, SP - Brazil

^[2] State Univ Campinas UNICAMP, Fac Appl Sci, Lab Metab Disorders, Limeira, SP - Brazil

^[3] Univ Estadual Campinas, Sch Appl Sci FCA, Multidisciplinary Lab Food & Hlth LabMAS, UNICAMP, Limeira, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROCHEMISTRY INTERNATIONAL; v. 139, OCT 2020.
• Citações Web of Science: 0

Resumo

Maternal high-fat diet (HFD) consumption can promote a systemic inflammatory condition that may impair the offspring brain development, damaging memory and learning, when it reaches the hippocampus. This study aims to evaluate maternal HFD effects, during pregnancy and lactation, upon dams/mice offspring nutritional status, protein and gene expression of inflammatory pathway (JNK, pJNK and TNF-alpha), serotonin system molecules (Tryptophan Hydroxylase 2 (TPH2), key-enzyme of serotonin synthesis, serotonin transporter (SERT); 5-HT1A serotonergic receptor (5-HT1A)) and brain derived neurotrophic factor (BDNF) on recently weaned mice offspring hippocampus. Female Swiss mice were fed a control diet (CD, 11,5% fat) or a HFD (45.0% fat) from premating to lactation. After weaning, the offspring received CD up to 28 post-natal days (PND28). Body weight and visceral adiposity (retroperitoneal and gonadal adipose tissue) of dams and offspring were measured. After euthanasia, the offspring hippocampus was dissected for evaluations of BDNF, inflammatory pathway and serotonergic system molecules protein and gene expression, through the techniques of Western Blotting, RTqPCR and ELISA. Our findings show that, during pregnancy, HFD-dams and HFD-offspring exhibited an increase in body weight gain and visceral adipose tissue compared to control animals. The hippocampus of HFD-offspring showed increased protein expression of TPH2, BDNF, pJNK and increased mRNA levels of TNF-alpha. However, the TPH2 increase in HFD-offspring did not alter hippocampal serotonin levels quantified through ELISA. Maternal HFD promoted an obesity phenotype in its offspring with increased body weight and visceral adiposity, increased protein and gene expression of the pro-inflammatory proteins pJNK and TNF-alpha. These changes were accompanied by increased TPH2 and BDNF protein expression. Thus, our findings show that maternal HFD during gestation and lactation increased pJNK and TNF-alpha expression in their offspring hippocampus indicating a proinflammatory state, with increased BDNF expression and alterations in its serotonergic system reflected by increased TPH2 expression. (AU)

• Processo FAPESP: 18/14818-9 - Estudo de alvos moleculares importantes para o controle do metabolismo em câncer: a via da mTOR/S6K com papel central
• Beneficiário: Fernando Moreira Simabuco
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 15/08441-1 - Efeitos de dieta obesogênica sobre proteínas da via inflamatória e do sistema serotoninérgico: estudo in vivo, em hipocampos da prole de camundongos, e in vitro em cultura de neuroblastos
• Beneficiário: Clarissa Tavares Dias
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/26146-4 - Avaliação da exposição precoce a dieta obesogênica sobre proteínas envolvidas com a neurogênese: estudo in vivo, em hipocampos de camundongos adultos, e in vitro em cultura de neuroblastos
• Beneficiário: Cristiano Mendes da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular