Dexamethasone programs lower fatty acid absorption and reduced PPAR-gamma and fat/CD36 expression in the jejunum of the adult rat offspring

Author(s)

de Souza, Dailson Nogueira ^[1] ; Teixeira, Caio Jordao ^[1] ; Veronesi, Vanessa Barbosa ^[1] ; Murata, Gilson Masahiro ^{[2, 3]} ; Santos-Silva, Junia Carolina ^[1] ; Hecht, Fernanda Ballerini ^[1] ; Vicente, Julia Modesto ^[1] ; Bordin, Silvana ^[2] ; Anhe, Gabriel Forato ^[1]

Affiliation

^[1] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, 105 Alexander Flemming St, BR-13083881 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, 1524 Prof Linen Prestes Ave, ICB 1, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, Dept Med Clin, BR-01246403 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 265, JAN 15 2021.
• Web of Science Citations: 0

Abstract

The progeny of rats born and breastfed by mothers receiving dexamethasone (DEX) during pregnancy exhibits permanent reduction in body weight and adiposity but the precise mechanisms related to this programming are not fully understood. In order to clarify this issue, the present study investigated key aspects of lipoprotein production and lipid metabolism by the liver and the intestine that would explain the reduced adiposity seen in the adult offspring exposed to DEX in utero. Female Wistar rats were treated with DEX (0.1 mg/kg/day) between the 15th and the 21st days of pregnancy, while control mothers were treated with vehicle. Male offspring born to control mothers were nursed by either adoptive control mothers (CTL/CTL) or DEX-treated mothers (CTL/DEX). Male offspring born to DEX-treated mothers were nursed by either control mothers (DEX/CTL) or adoptive DEX-treated mothers (DEX/DEX). We found that only the male DEX/DEX offspring had reduced adiposity. Additionally, male DEX/DEX progeny had lower circulating triacylglycerol (TAG) levels only in fed-state. The four groups of offspring presented similar energy expenditure, respiratory quotient and very low-density lipoprotein (VLDL) production. On the other hand, DEX/DEX rats displayed reduced TAG levels after gavage with olive oil and reduced expression of fatty acid translocase Cd36 (Fat/Cd36) and peroxisome proliferator-activated receptor gamma (Pparg) in the jejunum. Altogether, our study supports the notion that reduced fat absorption by the jejunum may contribute to the lower adiposity of the adult offspring born and breastfed by mothers treated with DEX during pregnancy. (AU)

• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/06397-3 - Study of cellular senescence in rodents subjected to Obesity
• Grantee: Caio Jordão Teixeira
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 19/03196-0 - Molecular mechanisms involved in the metabolic inflexibility of rats submitted to metabolic programming induced by prenatal excess of glucocorticoids
• Grantee: Silvana Auxiliadora Bordin da Silva
• Support type: Regular Research Grants
• FAPESP's process: 16/13138-9 - Effect of PPAR-gamma or PPAR-alpha agonists on the metabolic programing induced by maternal caloric restriction
• Grantee: Vanessa Barbosa Veronesi
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/23285-6 - Endocrine pancreas maturation and differentiation in offspring of females submitted to dexamethasone treatment during pregnancy
• Grantee: Junia Carolina Rebelo dos Santos Silva
• Support type: Scholarships in Brazil - Post-Doctorate