TABLE 4.

Various models for ceramide metabolism.

Transgenic model	Effects	Mechanism	Ceramide’s targets	References
Mice that overexpress long-chain acyl-CoA synthetase in the heart	Initial cardiac hypertrophy and cardiac dysfunction	Lipid accumulation associated with an increase in ceramide synthesis in cardiac tissues	—	Chiu et al. (2001)
Cardiac overexpression of glycosylphosphatidylinositol -anchored human lipoprotein lipase	Dilated cardiomyopathy	Increase the de novo biosynthesis of ceramides and accumulation of ceramide in heart tissues	SPT inhibitors, e.g., Myriocin	Park et al. (2008)
APPL1 overexpression in transgenic mice	Showed protection against cardiac dysfunction induced by high-fat-diet	Regulation of adiponectin and insulin signaling	—	Park et al. (2013)
	Increased insulin sensitivity	Also decreased ceramide in favor of sphingomyelin biosynthesis in cardiac tissues
Mutated (V717I) amyloid β precursor protein (AβPP) transgene in mouse hippocampus	Upregulation of ceramide synthesis in brain tissues that promote Alzheimer disease	Upregulation of ceramide synthases (increase ceramide turnover in the salvage pathway) and downregulation of sphingomyelin synthases	FTY720 counteracts reduction of sphingomyelin synthases and decrease of mRNA expression of ceramide synthases	Jęśko et al. (2020)
Transgenic mice with overexpression acid sphingomyelinase in hippocampus	Upregulation of ceramide production in the hippocampus enhanced depression-like behavior	Reduction in Akt phosphorylation at Ser473, which known to regulate neurogenesis	Functional inhibitor of acid sphingomyelinase (FIASMAs) e.g., Antidepressant drugs GW4869	Park et al. (2008); Kornhuber et al. (2014)

FTY720, fingolimod; SPT, serine palmitoyltransferase.