Table 2.

Deletion of specific genes, enzymes or supplementation with a specific diet helps to decrease the concentration of ceramides. sphingomyelin (SM); sphingosine kinase 1 (SPHK1); sphingosine kinase 2 (SPHK2); ceramide synthase 2 (CerS2); ceramide synthase 5 (CerS5); ceramide synthase 6 (CerS6); fruit and vegetables (FRUVED); low refined carbohydrates (LRC); ceramide (Cer); triglycerides (TG); alanine-aminotransferase (ALT); aspartate transaminase (AST); dihydroceramide desaturase (DES); Adenosine 5’-triphosphate (ATP); control group (Ctrl); fatty acid elongase 6 (Elovl6); ceramide synthase 1 (CERS1); carnitine palmitoyltransferase 1A (CPT1A); carnitine palmitoyltransferase (CPT2); serine palmitoyltransferase long chain base subunit 2 (Sptlc2).

Main Focus	Species	Outcomes	Year	Ref.
Fumonisine B1	Mice	60% reduction of hepatic SM levels (p < 0.05), increase expression of hepatic SPT (p < 0.01); SPHK 1 maximal at the lowest dose of 0.75 mg/kg (p < 0.05), expression of SPHK2 not affected;	2006	[92]
Elovl6	Mice	Reduced: Ceramide(d18:1/18:0)(0.63, p < 0.001); ceramide (d18:2/18:0) (1.68, p < 0.05), oleate (C18:1n-9) and stearate (C18:0);	2020	[150]
CerS2	Mice	Reduced lipid accumulation, sphingomyelin levels ~50%, uptake in the liver, reduction in very long chain acyl ceramides, enzymatic activity-decreased;	2015	[151]
CerS6	Mice	Reduce C16:0 ceramides, serum insulin concentrations, protects from macrophage infiltration, activation of pro-inflammatory gene expression; improve glucose tolerance and insulin sensitivity; reduced adiposity and increased energy expenditure, (p < 0.05);	2014	[152]
Diet	Human	Ceramides C22:0, C24:1; C26:0 reduced-29%, (p < 0.05), C24:0 50%, (p < 0.01); at week 8 increase of C16:0 (p < 0.05);	2017	[76]
P053	Mice	5 mg/kg/day reduced C18 ceramide by 31%, (p < 0.01); Reduces whole-body fat mass and the weight of white adipose depots;	2018	[17]
GW4869	Mice	Decrease of: the atherosclerotic area, accumulation of macrophages by 68%; atherosclerotic lesions by 69% (p < 0.001), in plasma Cer24:1, Cer22:0, and Cer24:0, (p < 0.05), lipid accumulation by 68% (p < 0.01);	2018	[121]
CerS1	Mice	The sphingolipid content in heart, liver, and white adipose tissue—not affect, imprivement of liver glucose metabolism, 95% reduction in C18:0 ceramide;	2019	[153]
CerS5	Mice	Improves glucose tolerance, insulin sensitivity, reduces white adipose inflammation, In skeletal muscle without obvious decrease;	2019	[153]
Bortezomib	Mice	Increase hepatic CerS2 expression, protects from development of NAFLD, decreases weight gain, TG levels lower (p < 0.01);	2019	[154]
Exendin-4	Mice	Decrease lobular inflammation (p = 0.18), fibrosis stages (p = 0.24)	2019	[155]
DEGS1 gene	Mice	Decreased: Cer16:0–0.09, Cer18:0–0.1 (p < 0.001), whole-body insulin sensitivity-restored, selective insulin resistance-reversed in the liver (p < 0.001);	2019	[115]
Myriocin	Rats	Reduced: serum ceramide content reduced, (p < 0.05), hepatic triglyceride, ALT, AST, hepatic inflammation, amount of inflammatory cell; Bcl-2 expression restored, (p < 0.05);	2019	[87]
Fenretinide	Mice	Lowered: plaque area 50.8% (p < 0.05), plasma lipid levels by 20.1%, (p < 0.05), and plasma ceramides;	2020	[156]
Diet	Mice	Flinax reduced lipoperoxidation markers, hepatic fat accumulation restores complex I, III, V (ATP-synthase), lower peroxides levels, (p < 0.05), no difference in complex IV, and higher production of CPT1A and CPT2;	2021	[148]
Alpha-mangostin	Mice	Inhibits: ceramide content, and, Inhibites aSMase activity,	2021	[146]
Farnesoid X receptor	Mice	Lower: ceramide content, hepatic cholesterol levels, mRNA levels of Smpd3 elevates hepatic Cyp7a1 mRNA levels Repressed lesion areas in aortas and smaller atherosclerotic lesions;	2021	[120]
Liraglutide	Mice	Gene expression Sptlc2, cerS4, and cerS6 decreased; C16 and C24 accumulation was limited (p < 0.05); Unchanged: saturated fatty acid, phospholipids with long chains-reduced, phospholipids with very long chains	2021	[132]