TREM2 has a significant, gender-specific, effect on human obesity

Reich, Tzila; Adato, Orit; Kofman, Naomi Schneid; Faiglin, Ariel; Unger, Ron

doi:10.1038/s41598-022-27272-x

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…Microglial phagocytosis of myelin debris plays a vital role in demyelinating diseases. Since the main component of myelin is neutral lipids, cholesterol, and glycosphingolipids, Trem2, as a lipid sensor, can mediate the phagocytosis of myelin by microglia (Reich et al, 2023;van Eijk & Aerts, 2021). However, while our study offers initial evidence for the interplay between Trem2 in microglia and oligodendrocytes, a deeper investigation is required to elucidate the underlying mechanisms.…”

Section: Trem2 Knockout Reduces the Accumulation Of Lipid Droplets In...mentioning

confidence: 90%

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Trem2 deficiency attenuates microglial phagocytosis and autophagic‐lysosomal activation in white matter hypoperfusion

Pang,

Chu,

Zhou

et al. 2023

Journal of Neurochemistry

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Chronic cerebral hypoperfusion leads to sustained demyelination and a unique response of microglia. Triggering receptor expressed on myeloid cells 2 (Trem2), which is expressed exclusively on microglia in the central nervous system (CNS), plays an essential role in microglial response in various CNS disorders. However, the specific role of Trem2 in chronic cerebral hypoperfusion has not been elucidated. In this study, we investigated the specific role of Trem2 in a mouse model of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis (BCAS). Our results showed that chronic hypoperfusion induced white matter demyelination, microglial phagocytosis, and activation of the microglial autophagic‐lysosomal pathway, accompanied by an increase in Trem2 expression. After Trem2 knockout, we observed attenuation of white matter lesions and microglial response. Trem2 deficiency also suppressed microglial phagocytosis and relieved activation of the autophagic‐lysosomal pathway, leading to microglial polarization towards anti‐inflammatory and homeostatic phenotypes. Furthermore, Trem2 knockout inhibited lipid droplet accumulation in microglia in vitro. Collectively, these findings suggest that Trem2 deficiency ameliorated microglial phagocytosis and autophagic‐lysosomal activation in hypoperfusion‐induced white matter injury, and could be a promising target for the treatment of chronic cerebral hypoperfusion.image

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Section: Trem2 Knockout Reduces the Accumulation Of Lipid Droplets In...mentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Trem2 deficiency attenuates microglial phagocytosis and autophagic‐lysosomal activation in white matter hypoperfusion

Pang,

Chu,

Zhou

et al. 2023

Journal of Neurochemistry

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“…These mechanisms contribute to the comprehension of how bariatric surgery orchestrates a signi cant transition from in ammation to metabolism. TREM2, a membrane protein expressed on immune cells, is implicated in neurodegenerative diseases and cancer [31]. Metabolic symptoms, including adipocyte hypertrophy, hypercholesterolaemia, fat accumulation, and glucose intolerance, are observed in TREM2 knockout mice [32].…”

Section: Discussionmentioning

confidence: 99%

Identification of the critical genes and signaling pathways in subcutaneous adipose tissue after bariatric surgery based on the GEO database

Han,

Wang,

Wang

et al. 2024

Preprint

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This study aimed to explore potential biomarkers and mechanisms following bariatric surgery. Two gene expression profiles from the Gene Expression Omnibus (GEO) were analysed to identify differentially expressed genes (DEGs) in subcutaneous adipose tissue (AT) post-bariatric surgery. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene-Set Enrichment Analysis (GSEA), and Protein-Protein Interaction (PPI) network analyses were employed to identify hub genes and associated pathways. Among the DEGs, 29 genes were downregulated. Enrichment analysis revealed that the downregulated DEGs significantly participated in inflammatory responses. GSEA provided comprehensive evidence that most genes were enriched in pro-inflammatory pathways before surgery, while after surgery, most genes were enriched in metabolism. In the PPI network, five key genes, including TREM2, MNDA, HP, C5AR1, and S100A8, were identified, with most validated as highly expressed in obesity by the Attie Lab Diabetes and another dataset, GSE72158. Bariatric surgery induces a significant shift from an obesity-promoting inflammatory state to an anti-inflammatory state, accompanied by improvements in adipocyte metabolic function. This represents a key mechanism for the enhancement of adipose tissue function following bariatric surgery. This study deepens the understanding of the benefits of bariatric surgery and provides potential biomarkers or therapeutic targets.

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“…A recent report provides evidence that ATM accumulate lipids in obese mice and become polarized toward the lipid-associated macrophages (LAM) state [ 62 ]. LAM development is driven by Trem2 and characterized by upregulation of components of an enzymatic machinery that recognizes, scavenges, and catabolizes lipids such as fatty acids transporter Cd36, fatty acid binding proteins 5 (Fabp5) and lipoprotein lipase (Lpl).…”

Section: Discussionmentioning

confidence: 99%

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction

Henry,

Barrett,

Vaida

et al. 2024

J Neuroinflammation

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Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular populations in the cortex and hippocampus, as well as in VAT, during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in selected gene expression signatures and pathways. Furthermore, combined TBI and HFD caused additive dysfunction in Y-Maze, Novel Object Recognition (NOR), and Morris water maze (MWM) cognitive function tests. These novel data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and VAT, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Thus, targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue immune cell populations, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.

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TREM2 has a significant, gender-specific, effect on human obesity

Cited by 12 publications

References 15 publications

Trem2 deficiency attenuates microglial phagocytosis and autophagic‐lysosomal activation in white matter hypoperfusion

Trem2 deficiency attenuates microglial phagocytosis and autophagic‐lysosomal activation in white matter hypoperfusion

Identification of the critical genes and signaling pathways in subcutaneous adipose tissue after bariatric surgery based on the GEO database

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction

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