Metabolic Dysfunction in the Regulation of the NLRP3 Inflammasome Activation: A Potential Target for Diabetic Nephropathy

Table 1

Aberrant metabolites activate the NLRP3 inflammasome in kidney-associated cells.

Stimulus	Kidney-related cells	Mechanism	Ref.
Glucose ↑	Monocytes	K^+ outflow, Ca^2+ inward flow/ROS/NLRP3 inflammasome	[14, 15]
	Glomerular mesangial cells	ROS/p38/FOXO1/TXNIP/NLRP3	[17–19]
		P50(NF-κB)/NLRP3 inflammasome	[20]
	Macrophages	PKM2/NLRP3 inflammasome	[21]
Saturated fatty acids ↑	Macrophages	Lysosomal destabilization/NLRP3 inflammasome	[26]
		AMPK/ROS/NLRP3 inflammasome	[27, 55]
Cholesterol ↑	Macrophages	Lysosomal destabilization/histone B/NLRP3 inflammasome/IL-1β	[34]
		ER to Golgi translocation/SREBP2/NLRP3 inflammasome	[35, 36]
Uric acid ↑	Macrophages	ROS/NLRP3/IL-1β/NF-κB	[40]
	Macrophages	ROS/TXNIP/NLRP3/caspase	[43]
Homocysteine ↑	Vascular endothelial cells	HMGB1/cathepsin V/NLRP3/caspase-1	[47]

ROS: reactive oxygen species; TXNIP: thioredoxin-interacting protein; FOXO1: forkhead box protein O1; NF-κB: nuclear factor kappa B; PKM2: pyruvate kinase M2; AMPK: adenosine 5-monophosphate-activated protein kinase; ER: endoplasmic reticulum; SREBP2: sterol regulatory element-binding protein 2; HMGB1: high mobility group box-1 protein; HIF1α: hypoxia inducible factor-1α; PDK1: 3-phosphoinositide-dependent kinase-1.