Fenofibrate treatment during lactation prevents liver and adipose tissue associated metabolic dysfunction in a rat model of childhood obesity
Childhood obesity and associated comorbidities in adulthood are of great concern worldwide. Evidence highlights the importance of lactation in later disease development. In this sense, obese children are at great risk of developing adult obesity, insulin resistance, type 2 diabetes, and cardiovascular disease at adulthood. PPARα activation during lactation promotes the expression of key enzymes involved in lipid oxidation, and it was associated with reduced adiposity in children. Therefore, we hypothesized that an animal model of childhood obesity, small litter (SL), would lead to the development of obesity and metabolic dysfunction in adulthood, which could be prevented by postnatal PPARα agonism. Wistar dams had their litter reduced, leading to postnatal overfeeding and obesity early in life. SL male pups were treated with fenofibrate, an PPARα agonist, during lactation, from postnatal day (PND) 1 until weaning (PND21), to verify whether PPARα activation prevents the developmental programming at adulthood (PND120). Childhood obesity induced by postnatal overfeeding leads to decreased markers for oxidative metabolism during infancy, leading to increased visceral adiposity and oxidative stress, insulin resistance, hepatic microvesicular steatosis, and increased fibroblast growth factor 21 (Fgf21) expression, followed by decreased brown adipose tissue (BAT) sympathetic nerve activity and decreased Fgfr1 hypothalamic expression in adulthood. Agonist-induced PPARα activation during lactation mitigated the development of aforementioned alterations in adulthood. Postnatal fenofibrate treatment prevents the developmental programming of visceral obesity, liver-associated metabolic dysfunction and BAT autonomic sympathetic hypoactivity in an animal model of childhood obesity.
Authors
- Jones Bernardes Graceli (ORCID: https://orcid.org/0000-0001-9349-4369)
- Jurandir Fernando Comar (ORCID: https://orcid.org/0000-0002-9518-7589)
- Josep C. Jiménez‐Chillarón (ORCID: https://orcid.org/0000-0002-0648-8049)
- Douglas Lopes Almeida (ORCID: https://orcid.org/0000-0002-1596-9821)
- Silvano Piovan (ORCID: https://orcid.org/0000-0002-0314-3838)
- Lucas Paulo Jacinto Saavedra (ORCID: https://orcid.org/0000-0003-0825-426X)
- Maria Natália Chimirri Peres
- Andreia Amaro (ORCID: https://orcid.org/0000-0002-0959-6571)
- Diana Sousa (ORCID: https://orcid.org/0000-0002-7989-7230)
- Naiara Cristina Lucredi (ORCID: https://orcid.org/0000-0003-4565-8028)
- Letícia Ferreira Barbosa (ORCID: https://orcid.org/0000-0002-5252-5883)
- Scarlett Rodrigues Raposo (ORCID: https://orcid.org/0000-0003-2685-420X)
- Veridiana Mota Moreira (ORCID: https://orcid.org/0000-0002-0502-6029)
- Flávia C.F. Dos Santos (ORCID: https://orcid.org/0000-0002-6972-9487)
- Rodrigo Mello Gomes (ORCID: https://orcid.org/0000-0002-9012-3287)
- Géssica Dutra Gonçalves (ORCID: https://orcid.org/0000-0003-3180-5437)
- Marcos Divino Ferreira-Junior (ORCID: https://orcid.org/0000-0003-0490-1212)
- Paulo Matafome (ORCID: https://orcid.org/0000-0002-3422-290X)
- Paulo Cézar de Freitas Mathias (ORCID: https://orcid.org/0000-0001-6994-4585)
- Ana Letícia Manso Assakawa
Institutions
- Southern Illinois University Carbondale (US)
- Universidade Estadual de Maringá (BR)
- Hospital Sant Joan de Déu Barcelona (ES)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Universidade Estadual do Oeste do Paraná (BR)
- Polytechnic Institute of Coimbra (PT)
- Universidade Federal do Espírito Santo (BR)
- University of Coimbra (PT)
Publication Details
- Journal
- Biomedicine & Pharmacotherapy
- Published
- 2025-05-19
- DOI
- https://doi.org/10.1016/j.biopha.2025.118166
- Primary Topic
- Fibroblast Growth Factor Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico