Deletion of lysophosphatidylcholine acyltransferase 3 in myeloid cells worsens hepatic steatosis after a high-fat diet

Thibaut Bourgeois; Antoine Jalil; Charles Thomas; Charlène Magnani; Naig Le Guern; Thomas Gautier; Jean-Paul Pais de Barros; Victoria Bergas; Hélène Choubley; Loïc Mazzeo; Louise Menegaut; Lorène J Lebrun; Kévin van Dongen; Marion Xolin; Tony Jourdan; Chloé Buch; Jérome Labbé; Philippe Saas; Laurent Lagrost; David Masson; Jacques Grober

doi:10.1194/jlr.RA120000737

Journal articles

Deletion of lysophosphatidylcholine acyltransferase 3 in myeloid cells worsens hepatic steatosis after a high-fat diet

Thibaut Bourgeois ^{1, 2} Antoine Jalil ^{1, 2} Charles Thomas ^{1, 2} Charlène Magnani ^{1, 2} Naig Le Guern ^{1, 2} Thomas Gautier ^{1, 2} Jean-Paul Pais de Barros ^{1, 2, 3} Victoria Bergas ^{1, 2, 3} Hélène Choubley ^{1, 2, 3} Loïc Mazzeo ^{1, 2} Louise Menegaut ^{1, 2} Lorène J Lebrun ^{1, 2, 4} Kévin van Dongen ^{1, 2} Marion Xolin ^{1, 2} Tony Jourdan ^{1, 2} Chloé Buch ^{1, 2} Jérome Labbé ^{1, 2} Philippe Saas ⁵ Laurent Lagrost ^{1, 2, 6} David Masson ^{1, 2, 6} Jacques Grober ^{1, 2, 4}

1 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]

2 LabEx LipSTIC - Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer

3 LAP - Plateforme Lipidomique [Dijon]

LNC - Lipides - Nutrition - Cancer (U866), IFR100 - Structure fédérative de recherche Santé-STIC, CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand

4 AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

5 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)

6 Laboratoire de biochimie médicale (CHU Dijon)

Abstract : Recent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell-membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated LPCAT3's role in macrophages both in vitro and in vivo in mice with atherosclerosis and obesity. To accomplish this, we used the LysMCre strategy to develop a mouse model with conditional Lpcat3 deficiency in myeloid cells (Lpcat3KOMac). We observed that partial Lpcat3 deficiency (approximately 75% reduction) in macrophages alters the PUFA composition of all phospholipid (PL) subclasses, including phosphatidylinositols and phosphatidylserines. A reduced incorporation of C20 PUFAs (mainly arachidonic acid [AA]) into PLs was associated with a redistribution of these FAs toward other cellular lipids such as cholesteryl esters. Lpcat3 deficiency had no obvious impact on macrophage inflammatory response or endoplasmic reticulum (ER) stress; however, Lpcat3KOMac macrophages exhibited a reduction in cholesterol efflux in vitro. In vivo, myeloid Lpcat3 deficiency did not affect atherosclerosis development in LDL receptor deficient mouse (Ldlr-/-) mice. Lpcat3KOMac mice on a high-fat diet displayed a mild increase in hepatic steatosis associated with alterations in several liver metabolic pathways and in liver eicosanoid composition. We conclude that alterations in AA metabolism along with myeloid Lpcat3 deficiency may secondarily affect AA homeostasis in the whole liver, leading to metabolic disorders and triglyceride accumulation.

Keywords : arachidonic acid atherosclerosis inflammation insulin resistance lipid metabolism lysophosphatidylcholine acyltransferase 3 (LPCAT3) macrophages obesity phospholipid steatosis

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Food engineering

Life Sciences [q-bio] / Food and Nutrition

Complete list of metadatas

https://hal-agrosup-dijon.archives-ouvertes.fr/hal-03134828
Contributor : Admin Agrosupdijon <>
Submitted on : Monday, February 8, 2021 - 3:09:14 PM
Last modification on : Thursday, February 11, 2021 - 5:29:08 PM

Deletion of lysophosphatidylcholine acyltransferase 3 in myeloid cells worsens hepatic steatosis after a high-fat diet

Links full text

Identifiers

Collections

Citation

Export

Metrics

35

Deletion of lysophosphatidylcholine acyltransferase 3 in myeloid cells worsens hepatic steatosis after a high-fat diet

Links full text

Identifiers

Collections

Citation

Export

Share

Metrics

35