Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease.
Circulating levels of four adipokines (adiponectin, TNF-alpha, leptin, and resistin) and the postprandial lipid and adiponectin responses to an oral fat load were assessed in 25 non-obese, non-diabetic patients with biopsy-proven nonalcoholic steatohepatitis (NASH) and correlated with metabolic indices and liver histology. Circulating adiponectin was lower in NASH compared with controls (5,476 +/- 344 vs. 11,548 +/- 836 ng/mL; P = .00001) and on multiple regression analysis correlated negatively with liver steatosis, necroinflammation (OR = 5.0; P = .009), and fibrosis (OR = 8.0; P = .003). The magnitude of postprandial lipemia was significantly higher in NASH than in controls and was related to fasting adiponectin (beta = -0.78; P = .00003). Controls showed a significant increase in serum adiponectin in response to the fat load, whereas patients with NASH showed a slight decrease. Postprandial free fatty acids response correlated inversely with adiponectin response in both groups and independently predicted the severity of liver steatosis in NASH (beta = 0.51; P = .031). In conclusion, hypoadiponectinemia is present before overt diabetes and obesity appear and correlates with the severity of liver histology in NASH. Impaired postprandial lipid metabolism may be an additional mechanism linking hypoadiponectinemia and NASH and posing a higher cardiovascular risk to these subjects. The mechanism(s) underlying these differences are unknown, but the type of dietary fat seems to play a role. These findings may have important pathogenetic and therapeutic implications in both liver and metabolic disease.
Musso
Giovanni
G
Department of Internal Medicine, University of Turin, Turin, Italy. giovanni_musso@yahoo.it
Gambino
Roberto
R
Durazzo
Marilena
M
Biroli
Giampaolo
G
Carello
Monica
M
Fagà
Emanuela
E
Pacini
Giovanni
G
De Michieli
Franco
F
Rabbione
Laura
L
Premoli
Alberto
A
Cassader
Maurizio
M
Pagano
Gianfranco
G
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000886:Anthropometry; D016207:Cytokines / Q000097:blood; D015930:Diet Records; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D020738:Leptin / Q000097:blood*; D050356:Lipid Metabolism; D008297:Male; D019518:Postprandial Period; D052243:Resistin / Q000097:blood*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D052242:Adiponectin; D016207:Cytokines; D020738:Leptin; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha