Advances in paediatric nonalcoholic fatty liver disease: Role of lipidomics

Table 1 Comparison between adult and paediatric lipidomic findings in nonalcoholic fatty liver disease

Lipid class	Changes in adult NAFLD patients	Changes in paediatric NAFLD patients
SFAs	Increased in liver[31] and in plasma[24]	Increased in liver and in plasma[32]
MUFAs	Increased in liver[35,36] and in plasma[25]	Increased in liver and in plasma[32]
PUFAs	Increased total PUFAs in liver[31] and n-6 LCPUFA in liver phospholipids[35]. Decreased LCPUFA of the n-6 and n-3 series in liver TAG, n-3 LCPUFA in phospholipids, total PUFA[35,36], n-3 PUFA[35], n-6 PUFA[32]	Increased in liver and in plasma[32]
PUFAs derived	Increased 5-HETE, 8-HETE, 11-HETE, and 15-HETE in NAFLD and NASH patients[27]. Increased 11,12-diHETrE, dhk PGD2, 20-COOH AA in NASH patients[26]	Increased EDPs, EEQs, EETs with progression of steatosis; reduced with progression of fibrosis[32]
TAG	Increased in liver[31] and in plasma[25]	Increased (TG[O]); TG (O-52:0), TG (O-52:1), TG (O-52:2), TG (O-52:3), TG (O-54:1), TG (O-54:2), TG (O-56:1) and TG (O-56:2) in serum[19]
DAG	Increased in liver[31] and in plasma[25]	No available data
FC	Increased in liver[31]	No available data
PC	Reduced in the liver[31], conflicting data for changes in serum[28,29]	Reduced serum alkyl/alkenyl-phosphatidylcholine (PC[O]) levels[19]
LPC	No statistically significant changes in plasma and serum[28,29]	No available data
PE	Decreased in liver[22] and increased in serum of NASH patients[28]	Increased PE in serum[19]
LPE	Decreased in serum of patients with NAFLD and NASH[28]	Increased LPE (20:3) and LPE (22:5); decreased [LPE(O)]) in serum[19]
PS	Reduced in liver[22], increased in plasma[29]	No available data
PI	Reduced in liver[22], increased in plasma[29]	No available data
PL	No change in liver[56]; decreased in plasma of NASH patients[25,57]	No available data
SM	Conflicting results in NAFLD and NASH patients[22,28,29,31,37,51]	Increased SM (d39:0), SM (d41:0) in serum[19]
CE	Increased in liver and in plasma[51,64,65]	Increased in serum[20]

20-COOH AA: 20-carboxy arachidonic acid; CE: Ceramides; DAG: Diacylglycerols; dhk PGD2: 13,14-dihydro-15-keto prostaglandin D2; diHETrE: Dihydroxy-eicosatrienoic acid; EDP: Epoxyeicosapentaenoic acid; EET: Epoxyeicosatrienoic acid; EEQ: Epoxyeicosatetraenoic acid; FC: Free cholesterol; HETE: Hydroxyeicosatetraenoic acid; LCPUFA: Long chain polyunsaturated fatty acid; LPC: Lysophosphatidylocholine; LPE: Lysophosphatidylethanolamine; LPE(O): Alkyl/alkenyl-lysophosphatidylethanolamine; MUFAs: Monounsaturated fatty acids; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; PC: Phosphatidylcholine; PE: Phosphatidylethanolamine; PI: Phosphatidylinositol; PL: Plasmalogens; PS: Phosphatidylserine; PUFAs: Polyunsaturated fatty acids; SFAs: Saturated fatty acids; SM: Sphingomyelin; TAG: Triacylglycerols; TG(O): Alkyl-diacylglycerols.

Table 2 Main findings of lipidomic studies in paediatric nonalcoholic fatty liver disease

Ref.	Study design and methods	Population (n)	Main findings
Wasilewska et al[20], 2018	Prospective study	80 children at median age 12 (7-17 yr)	Higher total serum CE concentration in NAFLD patients, compared to the controls and of certain CEs (C14:0, C16:0, C16:1, C18:0, C18:1, C22:0, C24:0). Total CE concentration was positively correlated with HOMA-IR and insulin levels
Draijer et al[8], 2020	Case-control study	21 children with obesity and steatosis and 21 with only obesity. Mean age of NAFLD patients: 14.8 yr; mean age of non-NAFLD patients 14.7 yr	Statistically significant alterations in 5 major lipid classes [TG(O), PE, PE(O), LPE(O), PC(O)] and 12 individual lipid species
Kalveram et al[32], 2021	Prospective study	40 children with biopsy-proven NAFLD. Mean age 14.2 ± 2.3 yr	Hepatic epoxyeicosanoids levels increased with higher degrees of steatosis. CYP epoxygenase activity increased, protein level, and activity of sEH decreased. In contrast, hepatic epoxyeicosanoids decreased with higher stages of fibrosis, with a decrease of CYP epoxygenase activity and protein expression

CE: Ceramides; CYP: Cytochrome P450; HOMA-IR: Homeostasis model assessment; NAFLD: Nonalcoholic fatty liver disease; LPE(O): Alkyl/alkenyl-lysophosphatidylethanolamine; PC(O): Alkyl/alkenyl-phosphatidylcholine; PE: Phosphatidylethanolamine; PE(O): Alkyl/alkenyl-phosphatidylethanolamine; sEH: Soluble epoxide hydrolase; TG(O): Alkyl-diacylglycerols.