Hepatic Phospholipid Remodeling Modulates Insulin Sensitivity and Systemic Metabolism
Abstract: The liver plays a central role in regulating glucose and lipid metabolism. Aberrant insulin action in the liver is a major driver of selective insulin resistance, in which insulin fails to suppress glucose production but continues to activate lipogenesis in the liver, resulting in hyperglycemia and hypertriglyceridemia. The underlying mechanisms of selective insulin resistance are not fully understood. Here It is shown that hepatic membrane phospholipid composition controlled by lysophosphatidylcholine acyltransferase 3 (LPCAT3) regulates insulin signaling and systemic glucose and lipid metabolism. Hyperinsulinemia induced by high‐fat diet (HFD) feeding augments hepatic Lpcat3 expression and membrane unsaturation. Loss of Lpcat3 in the liver improves insulin resistance and blunts lipogenesis in both HFD‐fed and genetic ob/ob mouse models. Mechanistically, Lpcat3 deficiency directly facilitates insulin receptor endocytosis, signal transduction, and hepatic glucose production suppression and indirectly enhances fibroblast growth factor 21 (FGF21) secretion, energy expenditure, and glucose uptake in adipose tissue. These findings identify hepatic LPCAT3 and membrane phospholipid composition as a novel regulator of insulin sensitivity and provide insights into the pathogenesis of selective insulin resistance.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Hepatic Phospholipid Remodeling Modulates Insulin Sensitivity and Systemic Metabolism ; day:23 ; month:04 ; year:2023 ; extent:15
Advanced science ; (23.04.2023) (gesamt 15)
- Creator
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Tian, Ye
Mehta, Kritika
Jellinek, Matthew J.
Sun, Hao
Lu, Wei
Shi, Ruicheng
Ingram, Kevin
Friedline, Randall H.
Kim, Jason K.
Kemper, Jongsook Kim
Ford, David A.
Zhang, Kai
Wang, Bo
- DOI
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10.1002/advs.202300416
- URN
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urn:nbn:de:101:1-2023042515104806466392
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:56 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Tian, Ye
- Mehta, Kritika
- Jellinek, Matthew J.
- Sun, Hao
- Lu, Wei
- Shi, Ruicheng
- Ingram, Kevin
- Friedline, Randall H.
- Kim, Jason K.
- Kemper, Jongsook Kim
- Ford, David A.
- Zhang, Kai
- Wang, Bo
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