Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat.
BACKGROUND
Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established.


METHODS
In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intrahepatic fat accumulation using magnetic resonance imaging.


RESULTS
Elevated ALT (> 35 U/liter) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18-35 U/liter). When hepatic fat fraction was assessed using fast magnetic resonance imaging, 32% of subjects had an increased hepatic fat fraction, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep to superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver.


CONCLUSIONS
Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.
Burgert
Tania S
TS
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Taksali
Sara E
SE
Dziura
James
J
Goodman
T Robin
TR
Yeckel
Catherine W
CW
Papademetris
Xenophon
X
Constable
R Todd
RT
Weiss
Ram
R
Tamborlane
William V
WV
Savoye
Mary
M
Seyal
Aisha A
AA
Caprio
Sonia
S
D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers; D015992:Body Mass Index; D002648:Child; D015331:Cohort Studies; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000033:anatomy & histology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000208:ethnology
D052242:Adiponectin; D015415:Biomarkers; D000410:Alanine Transaminase