Acute effects of fatty acids on autophagy in NPY neurones
| Autor: | Beatriz Piatezzi Siqueira, Letícia Martins Ignácio-Souza, Andressa Reginato, Adriana Souza Torsoni, Marcio Alberto Torsoni, Marciane Milanski, Mariana Portovedo, Hosana G. Rodrigues, Denise D. Belsham, Suleyma O. Costa, Hervé Le Stunff, Thaís de Fante, Josiane Érica Miyamoto |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Endocrinology Diabetes and Metabolism Hypothalamus Palmitic Acid Cellular homeostasis 030209 endocrinology & metabolism Diet High-Fat Energy homeostasis 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Myriocin Internal medicine medicine Autophagy Animals Neuropeptide Y Receptor Cells Cultured Neurons Endocrine and Autonomic Systems Chemistry Fatty Acids Neuropeptide Y receptor 3. Good health Lipotoxicity Saturated fatty acid 030217 neurology & neurosurgery |
| Zdroj: | Journal of neuroendocrinologyREFERENCES. 32(10) |
| ISSN: | 1365-2826 |
| Popis: | High-fat diet (HFD) feeding is deleterious to hypothalamic tissue, leading to inflammation and lipotoxicity, as well as contributing to central insulin resistance. Autophagy is a process that restores cellular homeostasis by degrading malfunctioning organelles and proteins. Chronic HFD-feeding down-regulates hypothalamic autophagy. However, the effects of short-term HFD-feeding and the saturated fatty acid palmitate (PA) on hypothalamic autophagy and in neurones that express neuropeptide Y (NPY) and agouti-related peptide remains unknown. Therefore, we assessed hypothalamic autophagy after 1 and 3 days of HFD-feeding. We also injected PA i.c.v and analysed the modulation of autophagy in hypothalamic tissue. Both interventions resulted in changes in autophagy-related gene profiles without significant differences in protein content of p62 and LC3B-II, markers of the autophagy pathway. When we assessed native NPY neurones in brain slices from PA-treated animals, we observed increased levels of Atg7 and LC3B protein in response to PA treatment, indicating the induction of autophagy. We then tested the direct effects of fatty acids using the immortalised hypothalamic NPY-expressing neuronal cell model mHypoE-46. We found that PA, but not palmitoleate (PO) (a monounsaturated fatty acid), was able to induce autophagy. Co-treatment with PA and PO was able to block the PA-mediated induction of autophagy, as assessed by flow cytometry. When the de novo ceramide synthesis pathway was blocked with myriocin pre-treatment, we observed a decrease in PA-mediated induction of autophagy, although there was no change with the toll-like receptor 4 inhibitor, TAK-242. Taken together, these findings provide evidence that saturated and unsaturated fatty acids can differentially regulate hypothalamic autophagy and that ceramide synthesis may be an important mediator of those effects. Understanding the mechanisms by which dietary fats affect autophagy in neurones involved in the control of energy homeostasis will provide potential new pathways for targeting and containing the obesity epidemic. |
| Databáze: | OpenAIRE |
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