Association of liver disease with postprandial large intestinal triglyceride-rich lipoprotein accumulation and pro/antioxidant imbalance in normolipidemic non-alcoholic steatohepatitis.
BACKGROUND
Dietary fat excess and antioxidant deficiency, altered lipid metabolism, and increased lipoperoxidation have been associated with non-alcoholic steatohepatitis (NASH), but the relative importance of each of these factors is unclear.


OBJECTIVE
To assess acute intestinal and hepatic very-low-density lipoprotein (VLDL) subfraction metabolism, lipid peroxidation, and pro/antioxidant imbalance after a fat load in NASH.


METHODS
Dietary habits, circulating adipokines, fasting and postprandial lipids, intestinal and hepatic VLDL, oxidized low-density lipoproteins (oxLDL), and total antioxidant status (TAS) were correlated to postprandial liver enzymes and to liver histology in 28 non-obese non-diabetic normolipidemic patients with NASH and 28 healthy controls.


RESULTS
Despite similar fasting profiles, NASH had more pronounced intestinal and hepatic VLDL1 accumulation, LDL lipid peroxidation and TAS fall postprandially. Postprandial intestinal VLDL1 independently predicted oxLDL and TAS responses in NASH. In NASH, hepatic steatosis was independently associated with postprandial intestinal VLDL1 and TAS; necroinflammation with postprandial serum gamma-glutamyltransferase, oxLDL and TAS responses; and fibrosis with adiponectin and postprandial TAS and oxLDL responses.


CONCLUSIONS
Postprandial intestinal VLDL1 accumulation is associated with a pro-oxidant imbalance in normolipidemic non-diabetic NASH, and both correlate with the severity of liver disease. Modulating postprandial lipoprotein metabolism may be beneficial in NASH, even if normolipidemic.
Musso
Giovanni
G
Gradenigo Hospital, Turin, Italy. giovanni_musso@yahoo.it
Gambino
Roberto
R
De Michieli
Franco
F
Biroli
Giampaolo
G
Fagà
Emanuela
E
Pagano
Gianfranco
G
Cassader
Maurizio
M
D054392:Adipokines / Q000378:metabolism; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D016877:Oxidants / Q000378:metabolism; D019518:Postprandial Period; D012720:Severity of Illness Index; D014280:Triglycerides / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D054392:Adipokines; D000975:Antioxidants; D004041:Dietary Fats; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D016877:Oxidants; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D005723:gamma-Glutamyltransferase