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Short-term exposure to an obesogenic diet causes dynamic dysregulation of proteasome-mediated protein degradation in the hypothalamus of female rats.
McFadden, Taylor; Farrell, Kayla; Martin, Kiley; Musaus, Madeline; Jarome, Timothy J.
Afiliación
  • McFadden T; Department of Animal and Poultry Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
  • Farrell K; Department of Animal and Poultry Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
  • Martin K; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
  • Musaus M; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
  • Jarome TJ; Department of Animal and Poultry Science, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Nutr Neurosci ; 26(4): 290-302, 2023 Apr.
Article en En | MEDLINE | ID: mdl-35282800
OBJECTIVES: Previous work has shown that exposure to a high fat diet dysregulates the protein degradation process in the hypothalamus of male rodents. However, whether this occurs in a sex-independent manner is unknown. The objective of this study was to determine the effects of a short-term obesogenic diet on the ubiquitin-proteasome mediated protein degradation process in the hypothalamus of female rats. METHODS: We fed young adult female rats a high fat diet or standard rat chow for 7 weeks. At the end of the 7th week, animals were euthanized and hypothalamus nuclear and cytoplasmic fractions were collected. Proteasome activity and degradation-specific (K48) ubiquitin signaling were assessed. Additionally, we transfected female rats with CRISPR-dCas9-VP64 plasmids in the hypothalamus prior to exposure to the high fat diet in order to increase proteasome activity and determine the role of reduced proteasome function on weight gain from the obesogenic diet. RESULTS: We found that across the diet period, females gained weight significantly faster on the high fat diet than controls and showed dynamic downregulation of proteasome activity, decreases in proteasome subunit expression and an accumulation of degradation-specific K48 polyubiquitinated proteins in the hypothalamus. Notably, while our CRISPR-dCas9 manipulation was able to selectively increase some forms of proteasome activity, it was unable to prevent diet-induced proteasome downregulation or abnormal weight gain. CONCLUSIONS: Collectively, these results reveal that acute exposure to an obesogenic diet causes reductions in the protein degradation process in the hypothalamus of females.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aumento de Peso / Complejo de la Endopetidasa Proteasomal Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Nutr Neurosci Asunto de la revista: CIENCIAS DA NUTRICAO / NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aumento de Peso / Complejo de la Endopetidasa Proteasomal Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Nutr Neurosci Asunto de la revista: CIENCIAS DA NUTRICAO / NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido