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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: NEUROCHEMISTRY INTERNATIONAL; v. 139, OCT 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 18/14818-9 - Study of molecular targets important for the control of cancer metabolism: the mTOR/S6K pathway as a central role
• Grantee: Fernando Moreira Simabuco
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 15/08441-1 - Effects of high-fat diet on proteins of the inflammatory pathway and from serotonergic system: study in vivo in mice offspring's hippocampus and in vitro in neuroblasts (neuro-2a cells)
• Grantee: Clarissa Tavares Dias
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/26146-4 - Assessment of early exposure to high-fat diet on protein involved in neurogenesis: studies, in vivo in hippocampus of adult mice and in vitro in neuroblast
• Grantee: Cristiano Mendes da Silva
• Support Opportunities: Regular Research Grants