Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner

In the citing paper

“MASH is associated with the emergence of lipid-associated macrophages (LAM) that highly express Trem2 along with Cd9, Gpnmb, and Spp1 (3–5)”

In the citing paper

“While the majority of murine studies to date have suggested a role for LAMs/LAM-like KCs in tissue repair, contributing to dead cell and lipid clearance, thus reducing lipotoxic stress, and preventing uncontrolled inflammation (36, 108, 122–126)”

In the citing paper

“TREM2 ligands include a variety of molecules, such as bacterial wall products, Aβ oligomers, lipoproteins, and anionic lipids, such as phospholipids and sphingolipids29,32–35”

In the citing paper

“Notably, these included the lysosomal enzymes ASAH1, LIPA, CTSA, CTSG, CTSZ, PLA2G15 and PPT1, enzymes part of the Coordinated Lysosomal Expression and Regulation network60, as well as PLA2G7, previously associated with atherosclerotic plaques61 and with the LAM48 and MIMS-foamy microglial states11.”

In the citing paper

“The foamy, GPNMB+ microglial phenotype in MS lesions bears striking transcriptional similarity to LAMs in obesity, amyloid-responsive microglia in Alzheimer’s disease and foam cells in atherosclerosis18,46,48,50,51.”

In the citing paper

“The disease-associated phenotype of microglia seems to be shared by aging, as well as neurological and non-neurological diseases with different etiology, e.g. AD and amyotrophic lateral sclerosis (Holtman et al., 2015; Keren-Shaul et al., 2017), atherosclerosis and obesity, characterized by lipid overload (Jaitin et al., 2019; Martinet et al., 2019).”

In the citing paper

“There was considerable overlap between the Micro_D profile and previously reported microglial states, such as the MIMS-foamy state reported in ref. 11, amyloid-associated microglia in Alzheimer’s disease43,46,47 and lipid-associated macrophages (LAMs) in obesity48 (Extended Data Fig. 8).”

In the citing paper

“In the adipose tissue, TREM2 sustains the presence of a population of lipid-associated macrophages (LAMs) that prevent the dysmetabolism engendered by a high-fat diet (Jaitin et al., 2019).”

In the citing paper

“lipid-associated macrophages have recently been identified in mouse and human adipose tissue, where TREM2 expression was found to regulate lipid homeostasis [57].”

In the citing paper

“These cells had a similar transcriptional profile to DAM [57]”

In the citing paper

“although the mouse DAM transcriptome profile may not be fully present in AD brain, as human microglia show a distinct AD-related gene signature (Jaitin et al., 2019; Mathys et al., 2019).”

In the citing paper

“However, in experimental liver fibrosis in murine models, TREM2-deficient macrophages failed to acquire reparative phenotypes, showed impaired efferocytosis, and exacerbated fibrogenesis (36, 122–126).”

In the citing paper

“The finding of lipid droplet containing microglia in GRN−/− mice is corroborated by a recent study which showed that cultured progranulin-deficient macrophages exhibited increased foam cell formation, i.e. lipid droplet accumulation, compared to wild type macrophages49.”

In the citing paper

“These monocyte-derived/bone marrow-dependent macrophages in NASH livers share striking similarities with macrophages in related extrahepatic compartments such as the bone marrow or adipose tissue,72,73 including a subset of “lipid-associated macrophages” with a unique metabolically activated phenotype.74”

In the citing paper

“Second, monocyte-derived macrophages replace liver resident Kupffer cells that normally clear iron, resulting in iron overload, oxidative stress, and activation of HSCs into myofibroblasts (70, 74-77).”

In the citing paper

“In fatty liver, a novel subset of lipid-associated macrophages (LAMs) display a unique ability to metabolize lipids, but their contribution to fibrosis is unknown (70, 76).”