ArticleNutrition & metabolism2019
Hepatic PKA inhibition accelerates the lipid accumulation in liver.
Article in Nutrition & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 28 citations in OpenAlex.
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- The AKAP12-PKA axis regulates lipid homeostasis during alcohol-associated liver disease.Signal transduction and targeted therapy · 2025Article
- The effects and mechanisms of Xiaoyao San on nonalcoholic fatty liver disease rat based on transcriptomics and proteomics analysis.Scientific reports · 2025Article
- A set of downregulated pleiotropic genes are possible multi-omics biomarkers underlying the irritable bowel syndrome-non-alcoholic fatty liver disease comorbidity.American journal of translational research · 2025Article
- Loss of carnitine palmitoyltransferase 1a reduces docosahexaenoic acid-containing phospholipids and drives sexually dimorphic liver disease in mice.Molecular metabolism · 2023Article
- Novel Effect ofMolecules (Basel, Switzerland) · 2023Article
- High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities.Frontiers in endocrinology · 2023Article
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- Phosphorylation of 17β-hydroxysteroid dehydrogenase 13 at serine 33 attenuates nonalcoholic fatty liver disease in mice.Nature communications · 2022Article
- Hepatic kinome atlas: An in-depth identification of kinase pathways in liver fibrosis of humans and rodents.Hepatology (Baltimore, Md.) · 2022Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
aimsLiver lipid accumulation induced by high-fat diet (HFD) is an early onset process of non-alcoholic fatty liver diseases (NAFLD). Protein kinase A (PKA) is known to be involved in hepatic lipid metabolism. However, the role of PKA in NAFLD has not been well tested in vivo due to the lack of optimal PKA deficient mouse model.
methodsA novel PKA-specific inhibitor gene was conditionally overexpressed in mouse (PKAi mouse) liver using LoxP/Cre system. PKA activity in the liver extract was measured with a commercial assay kit. The PKAi and control mice of 8-week age, were subjected to HFD or chow diet (CD) for 2 months. Body weight, liver index, and triglyceride in the liver were measured. RNA sequencing was performed for the liver tissues and analyzed with Gene Ontology (GO) and pathway enrichment.
resultsPKAi-GFP protein was overexpressed in the liver and the PKA activation was significantly inhibited in the liver of PKAi mouse. When fed with CD, RNA sequencing revealed 56 up-regulated and 51 down-regulated genes in PKAi mice compared with control mice, which were mainly involved in lipid metabolism though no significant differences in the body weight, liver index, triglyceride accumulation were observed between PKAi and control mice. However, when fed with HFD for 2 months, the liver was enlarged more, and the accumulation of triglyceride in the liver was more severe in PKAi mice. When comparing the transcriptomes of CD-fed and HFD-fed control mice, GO enrichment showed that the genes down-regulated by HFD were mainly enriched in immune-related GO terms, and up-regulated genes were enriched in metabolism. When comparing the transcriptomes of CD-fed and HFD-fed PKAi mice, GO analysis showed that the down-regulated genes were enriched in metabolism, while the up-regulated genes were clustered in ER stress-related pathways. When comparing HFD-fed PKAi and HFD-fed control mice, the genes with lower expression level in PKAi mice were enriched in the lipoprotein synthesis, which might explain that more TG is accumulated in PKAi liver after HFD feeding.
conclusionsReduced PKA activity could be a factor promoting the TG accumulation in the liver and the development of NAFLD.
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