Pleiotrophin deficiency protects against high-fat diet-induced neuroinflammation: Implications for brain mitochondrial dysfunction and aberrant protein aggregation

Sánchez Alonso, María GraciaSevillano Fernández, JulioRamos Álvarez, María del PilarCañeque Rufo, HéctorZuccaro, AgataHerradón Gil-Gallardo, GonzaloUniversidad San Pablo-CEU. Facultad de Farmacia. Departamento de Ciencias Farmacéuticas y de la Salud2024-01-312024-01-312023-02Cañeque-Rufo H, Sánchez-Alonso MG, Zuccaro A, Sevillano J, Ramos-Álvarez M del P, Herradón G. Pleiotrophin deficiency protects against high-fat diet-induced neuroinflammation: Implications for brain mitochondrial dysfunction and aberrant protein aggregation [Internet]. Vol. 172, Food and Chemical Toxicology. 2023http://hdl.handle.net/10637/15254Acceso al texto completo del artículo, disponible desde el sitio de la revista usando DOI: https://doi.org/10.1016/j.fct.2022.113578Metabolic Syndrome (MetS) is a risk factor for the development of neurodegenerative diseases. Neuroinflammation associated with MetS may contribute significantly to neurodegeneration. Pleiotrophin (PTN) is a neurotrophic factor that modulates neuroinflammation and is a key player in regulating energy metabolism and thermogenesis, suggesting that PTN could be important in the connection between MetS and neuroinflammation. We have now used a high-fat diet (HFD)-induced obesity model in Ptn-/- mice. HFD and Ptn deletion caused alterations in circulating hormones including GIP, leptin and resistin. HFD produced in Ptn+/+ mice a neuroinflammatory state as observed in cerebral quantifications of proinflammatory markers, including Il1β, Tnfα and Ccl2. The upregulation of neuroinflammatory markers was prevented in Ptn-/- mice. Changes induced by HFD in genes related to mitochondrial biogenesis and dynamics were less pronounced in the brain of Ptn-/- mice and were accompanied by significant increases in the protein expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I and IV. HFD-induced changes in genes related to the elimination of protein aggregates were also less pronounced in the brain of Ptn-/- mice. This study provides substantial evidence that Ptn deletion protects against HFD-induced neuroinflammation, mitochondrial dysfunction, and aberrant protein aggregation, prominent features in neurodegenerative diseases.application/pdfenmetadata only accessMetabolic syndromeNeuroinflammationPleiotrophinPtprz1Pleiotrophin deficiency protects against high-fat diet-induced neuroinflammation: Implications for brain mitochondrial dysfunction and aberrant protein aggregationArtículo10.1016/j.fct.2022.113578https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es