ArticleNutritional neuroscience2023
Short-term exposure to an obesogenic diet causes dynamic dysregulation of proteasome-mediated protein degradation in the hypothalamus of female rats.
Article in Nutritional neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 2 citations in OpenAlex.
- Hypothalamic DNA 5-hydroxymethylation levels are altered by diet-induced weight gain during the development of obesity in a sex-specific manner.Brain research · 2023Article
- Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity.PloS one · 2023Article
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5 authors at 1 institution in 1 country.
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Abstract
objectivesPrevious 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.
methodsWe 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.
resultsWe 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.
conclusionsCollectively, 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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