{"doi":"10.1016/j.jlr.2023.100383","title":"Adipocyte phosphatidylinositol biosynthesis via the Lands cycle protects against insulin resistance","abstract":"MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasisJournal of Lipid ResearchVol. 64Issue 4PreviewWe previously demonstrated that antisense oligonucleotide-mediated knockdown of Mboat7, the gene encoding membrane bound O-acyltransferase 7, in the liver and adipose tissue of mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression in mice but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Full-Text PDF Open Access The Lands cycle, elucidated by Dr William (Bill) Lands, describes the recycling of phospholipids by addition of a fatty acyl chain to a lysophospholipid by lipid acyltransferases and cleavage of a fatty acyl chain to generate a lysophospholipid by phospholipases (1O'Donnell V.B. New appreciation for an old pathway: the Lands Cycle moves into new arenas in health and disease.Biochem. Soc. Trans. 2022; 50: 1-11Crossref PubMed Scopus (4) Google Scholar). Dr Lands published a series of elegant biochemical studies in the late 1950s to mid-1960s (e.g., (2Lands W.E. Metabolism of glycerolipids. 2. The enzymatic acylation of lysolecithin.J. Biol. Chem. 1960; 235: 2233-2237Abstract Full Text PDF PubMed Google Scholar)), describing these processes (Fig. 1). The Lands cycle allows a cell to remodel the acyl chain composition of its membrane phospholipids, and thereby its physical and functional properties (1O'Donnell V.B. New appreciation for an old pathway: the Lands Cycle moves into new arenas in health and disease.Biochem. Soc. Trans. 2022; 50: 1-11Crossref PubMed Scopus (4) Google Scholar). Such remodeling is critical, as recent research demonstrates a role for the Lands cycle in metabolic disease. One of the mammalian lysophospholipid acyltransferases is termed MBOAT7 (membrane bound O-acyltransferase domain containing 7). An updated nomenclature has recently been proposed, which renames MBOAT7 as LPLAT11 (lysophospholipid acyltransferase 11) (5Valentine W.J. Yanagida K. Kawana H. Kono N. Noda N.N. Aoki J. et al.Update and nomenclature proposal for mammalian lysophospholipid acyltransferases, which create membrane phospholipid diversity.J. Biol. Chem. 2022; 298101470Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar). MBOAT7 has attracted increased interest in the area of metabolic disease because genome-wide association studies have identified a susceptibility locus (rs641738) within a linkage-disequilibrium block that contains the MBOAT7 gene that associates with liver disease, including nonalcoholic fatty liver disease (6Varadharajan V. Massey W.J. Brown J.M. Membrane-bound O-acyltransferase 7 (MBOAT7)-driven phosphatidylinositol remodeling in advanced liver disease.J. Lipid Res. 2022; 63100234Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar). MBOAT7 is highly selective in esterifying lysophosphatidylinositol (LPI) to arachidonoyl-CoA (C20:4-CoA), generating phosphatidylinositol (PI[18:0/20:4]), as shown in Fig. 1. Consistent with the genome-wide association study, silencing MBOAT7 by an antisense oligonucleotide, which resulted in lower MBOAT7 expression primarily in liver, adipose tissue, and cells within the reticuloendothelial system, caused a nonalcoholic fatty liver disease phenotype in fat-fed mice (7Helsley R.N. Varadharajan V. Brown A.L. Gromovsky A.D. Schugar R.C. Ramachandiran I. et al.Obesity-linked suppression of membrane-bound O-acyltransferase 7 (MBOAT7) drives non-alcoholic fatty liver disease.Elife. 2019; 8e49882Crossref PubMed Scopus (53) Google Scholar). Although there were no detected differences in body weights or circulating lipoproteins, MBOAT7 silencing also resulted in insulin resistance, characterized by glucose intolerance, elevated plasma insulin and C-peptide levels, and a reduced abil","journal":"Journal of Lipid Research","year":2023,"id":381829,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299555,"name":"Karin Bornfeldt","orcid":"0000-0001-9208-6523","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T01:17:12.933204Z","pmid":"37127068","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}