Overexpression of lysophospholipid acyltransferase, LPLAT10/LPCAT4/LPEAT2, in the mouse liver increases glucose‐stimulated insulin secretion

Postprandial hyperglycemia is an early indicator of impaired glucose tolerance that leads to type 2 diabetes mellitus (T2DM). Alterations in the fatty acid composition of phospholipids have been implicated in diseases such as T2DM and nonalcoholic fatty liver disease. Lysophospholipid acyltransferase 10 (LPLAT10, also called LPCAT4 and LPEAT2) plays a role in remodeling fatty acyl chains of phospholipids; however, its relationship with metabolic diseases has not been fully elucidated. LPLAT10 expression is low in the liver, the main organ that regulates metabolism, under normal conditions. Here, we investigated whether overexpression of LPLAT10 in the liver leads to improved glucose metabolism. For overexpression, we generated an LPLAT10‐expressing adenovirus (Ad) vector (Ad‐LPLAT10) using an improved Ad vector. Postprandial hyperglycemia was suppressed by the induction of glucose‐stimulated insulin secretion in Ad‐LPLAT10‐treated mice compared with that in control Ad vector‐treated mice. Hepatic and serum levels of phosphatidylcholine 40:7, containing C18:1 and C22:6, were increased in Ad‐LPLAT10‐treated mice. Serum from Ad‐LPLAT10‐treated mice showed increased glucose‐stimulated insulin secretion in mouse insulinoma MIN6 cells. These results indicate that changes in hepatic phosphatidylcholine species due to liver‐specific LPLAT10 overexpression affect the pancreas and increase glucose‐stimulated insulin secretion. Our findings highlight LPLAT10 as a potential novel therapeutic target for T2DM.

• Publication year

  2024

• Venue

  The FASEB Journal

• Publication date

  2024-01-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1096/fj.202301594RRPMID 38226852
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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