ArticleNature communications2025
Hepatic AKAP1 deficiency exacerbates diet-induced MASLD by enhancing GPAT1-mediated lysophosphatidic acid synthesis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Norepinephrine attenuates acute lung injury by protecting mitochondria via the βRedox biology · 2026Article
- Indole-3-Propionic Acid Alleviates Metabolic Dysfunction-Associated Fatty Liver Disease via AHR/AMPK Signaling Activation.Food science & nutrition · 2026Article
- AKAP1 enhances glycogen accumulation and hepatocarcinogenesis through YTHDF2-mediated G6PC mRNA decay.Signal transduction and targeted therapy · 2026Article
- Using human genetics to understand the epidemiological association between child obesity at different ages and MASLD.International journal of surgery (London, England) · 2026Article
- Impact of Metabolic Dysfunction-Associated Steatotic Liver Disease on Fatigue and Pruritus in Primary Sclerosing Cholangitis: A U.S. Single-Center Study.Journal of clinical medicine · 2025Article
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11 authors.
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), closely associated with obesity, can progress to metabolic dysfunction-associated steatohepatitis when the liver undergoes overt inflammatory damage. A-kinase anchoring protein 1 (AKAP1) has been shown to control lipid accumulation in brown adipocytes. However, the role of AKAP1 signaling in hepatic lipid metabolism and MASLD remains poorly understood. Here, we showed that hepatocyte-specific AKAP1 deficiency exacerbated hepatic steatosis and steatohepatitis in male mice subjected to a high-fat diet and fast-food diet, respectively. Mechanistically, AKAP1 directly phosphorylated and inactivated glycerol-3-phosphate acyltransferase 1 (GPAT1) in a PKA-dependent manner, thus suppressing lysophosphatidic acid (LPA) production. Increased endogenous LPA in hepatocytes promoted hepatocellular triglyceride (TG) synthesis and initiated pronounced inflammatory response in Kupffer cells. Restoring hepatic AKAP1 or repressing LPA levels via GPAT1 knockdown alleviated MASLD exacerbation. Overall, AKAP1 plays a protective role against MASLD by inhibiting GPAT1 activity, highlighting the potential of targeting AKAP1/PKA/GPAT1 signalosome for MASLD therapy.
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