Macrophage and inflammation in diabetes and metabolic dysfunction-associated steatotic liver disease: From mechanisms to therapeutic strategies

Table 2 Important signaling pathways regulating macrophage differentiation and function during metabolic dysfunction-associated steatotic liver disease and type 2 diabetes pathogenesis[33,122-130]

Disease	Signaling pathway	Function	Ref.
MASLD	TRIM38-HSPA5 axis	Macrophage M2 polarization	Yang et al[122]
MASH	LPS-COX-2-PGE2	Macrophage inflammation	Vahrenbrink et al[123]
MASLD	Trem2	Macrophage pyroptosis and inflammation	Xiang et al[124]
MASLD	GPNMB	Retention of liver resident Kupffer cells and rerouting monocyte differentiation to Kupffer cell-resembling macrophages	Wang et al[33]
MASLD or MASH	Notch-RBPJ	Monocyte-to-macrophage transition	Guo et al[125]
MASLD	IRF5	Immunosuppressive and anti-apoptotic function	Alzaid et al[126]
T2D	PI3K/AKT/mTOR	Macrophage M2 polarization	Yang et al[127]
T2D	STING/Mef2D	Macrophage M2 polarization	Chen et al[128]
MASH, T2D	GDF-15	Regulation of obesity	L'homme et al[129]
T2D	Calreticulin	Macrophage transformation and accumulation	Zheng et al[130]

T2D: Type 2 diabetes; MASLD: Metabolic dysfunction-associated steatotic liver disease; MASH: Metabolic dysfunction-associated steatohepatitis; TRIM38: Tripartite motif containing 38; HSPA5: Heat shock protein family A member 5; LPS: Lipopolysaccharide; COX-2: Cyclooxygenase 2; PGE2: Prostaglandin E2; TREM2: Triggering receptor expressed on myeloid cells 2; GPNMB: Glycoprotein non-metastatic melanoma protein b; Notch: Neurogenic locus notch homolog protein; RBPJ: Recombination signal binding protein for immunoglobulin kappa J region; IRF5: Interferon regulatory factor 5; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; Mef2D: Myocyte enhancer factor 2D; STING: Stimulator of interferon response cyclic guanosinc monophosphate-adenosine 5’-monophosphate interactor 1; GDF-15: Growth differentiation factor-15.