How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease.
BACKGROUND
Adipose tissue contributes to nonalcoholic fatty liver disease (NAFLD), being a source of fatty acids and cytokines such as leptin and adiponectin, and regulating ghrelin production. Their role in NAFLD pathogenesis remains controversial. We aimed to study the influence of those cytokines on the severity of NAFLD.


METHODS
Morbidly obese individuals with biopsy-proven NAFLD were recruited. The NAFLD activity score was applied to liver histology. Serum concentrations of adiponectin, leptin, and ghrelin were determined.


RESULTS
Eighty-two patients were included, 13% with nonalcoholic steatohepatitis (NASH). Hypertriglyceridemia (P=0.018) and metabolic syndrome (P=0.040) were independent factors associated with NASH. Leptin associated positively and ghrelin associated negatively with BMI; adiponectin associated negatively with the waist to hip ratio. Adiponectin associated negatively with insulin resistance, hypertension, and metabolic syndrome; ghrelin associated positively with diabetes mellitus. Adiponectin below 23 ng/ml associated with NASH (odds ratio 12.95, P<0.001). Leptin increased progressively (P=0.032) and adiponectin decreased (P=0.004) with increasing severity of steatosis. Also, leptin increased progressively with more severe fibrosis (P=0.053). A formula incorporating the three cytokines yielded an AUROC of 0.789 (P=0.002), a sensitivity of 81.8%, and a specificity of 76.1% for NASH.


CONCLUSIONS
An imbalance in adiponectin, leptin, and ghrelin seems to be associated with more severe NAFLD. A formula combining the three cytokines showed good accuracy for NASH.
Department of Gastroenterology, Nutrition and Metabolism Unit, Hospital of Santa Maria, Molecular Medicine Institute, Lisbon Medicine University, Lisbon, Portugal.
Mariana V
MV
Machado
João
J
Coutinho
Fátima
F
Carepa
Adília
A
Costa
Helena
H
Proença
Helena
H
Cortez-Pinto
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000704:Analysis of Variance; D050110:Bariatric Surgery; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000097:blood / Q000209:etiology* / Q000473:pathology; D005260:Female; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications* / Q000473:pathology; D011446:Prospective Studies; D012372:ROC Curve; D012044:Regression Analysis; D012720:Severity of Illness Index
D052242:Adiponectin; D054439:Ghrelin; D020738:Leptin