Table 1.

Lipid and lipid metabolites that contribute to podocyte lipotoxicity

Class	Model	Outcome	Ref.
Saturated FAs
Palmitic acid (16:0)*	MPC, DKD mice	↑ Podocyte injury and apoptosis, mitochondrial dysfunction, oxidative stress, ER stress, insulin resistance; ↑ albuminuria	[27–32]
Stearic acid (18:0)*	CKD patients	Decreased abundance in plasma associate with declining renal function	[33]
Unsaturated FAs
Oleic acid (18:1)*	MPC, DKD mice	↓ Podocytes cell death and loss, ER stress, oxidative stress; ↑ proteasome expression; ↓ albuminuria, histologic changes	[28, 34]
Arachidonic acid (20:4)*	HPC	↑ Actin cytoskeleton remodeling, podocyte injury	[35]
Eicosapentaenoic acid (20:5)*	MPC	↓ Podocyte apoptosis, inflammation	[36]
Glycerolipids
Triglyceride	CKD, metabolic syndrome mice	↑ Podocyte apoptosis; ↑ albuminuria, histologic changes	[37]
Phospholipids
Phosphatidylcholine	MPC, DKD mice	Associate with podocyte injury and DKD	[38, 39]
Phosphatidylethanolamine	MPC, DKD mice	Associate with podocyte injury and DKD	[38, 39]
Cardiolipin	HPC, DKD mice	↑ Podocyte injury, mitochondrial dysfunction; ↑ albuminuria, histologic changes	[25]
Phosphosphingolipids
Sphingomyelin	DKD mice	↑ Actin cytoskeleton remodeling, podocyte injury; ↑ albuminuria, histologic changes	[40]
Glycosphingolipids
Ganglioside	HPC, MPC, DKD mice	↑ Actin cytoskeleton remodeling, podocyte injury; ↑ albuminuria, histologic changes	[41, 42, 43]
Other sphingolipids
Ceramide	DKD mice	↑ Mitochondrial dysfunction, inflammation, insulin resistance, podocyte injury	[42, 44, 45]
Sphingosine	Primary MPC, podocytopathy and associated NS mice (Asah1fl/fl/Podo-Cre mice)	↓ Exosome release of podocytes, podocyte injury; ↓ urinary exosome excretion	[46, 47]
Sphingosine-1-phosphate	CKD mice	↑ Albuminuria, histological changes; ↑ oxidative stress, mitochondrial dysfunction	[46, 48]
Ceramide-1-phosphate	HPC, DKD mice	↓ Inflammation, insulin resistance, podocyte apoptosis; ↓ albuminuria, histologic changes	[25, 40]
Sterol lipid
Cholesterol	HPC, HN mice	↑ Podocyte apoptosis; ↑ albuminuria, histologic changes	[49, 50]
Cholesterol esters	HPC, DKD mice, AS mice	↑ Podocyte injury; ↑ albuminuria, histologic changes	[51]

Ref., reference; MPC, mouse podocytes; DKD, diabetic kidney disease; CKD, chronic kidney disease; ER, endoplasmic reticulum; HPC, human podocytes; NS, nephrotic syndrome; KO, knockout; Podo, podocyte; HN, hypertensive nephropathy; AS, Alport syndrome. * Number of carbon atoms: number of C = C double bonds.