Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 19 P134

SFEBES2009 Poster Presentations Diabetes, Metabolism and Cardiovascular (49 abstracts)

Downregulation of hepatic glucose 6-phosphatase-alpha in patients with nonalcoholic fatty liver

S Konopelska , T Kienitz & M Quinkler


Clinical Endocrinology, Charite Campus Mitte, Berlin, Germany.


Background: Microsomal glucose-6-phosphatase-alpha (G6Pase-alpha) and glucose-6-phosphate transporter (G6PT) perform the terminal step in both glycogenolysis and gluconeogenesis. Deficiency of G6Pase-alpha leads to glycogen storage disease type 1a, whereas deficiency of G6PT leads to glycogen storage disease type 1b. Partial inhibition of G6Pase in rats results in increased hepatic triglyceride contents and de novo lipogenesis leading to hepatic steatosis. Hepatic steatosis (nonalcoholic fatty liver), affecting 34% of the US population, frequently represents a hepatic manifestation of the metabolic syndrome. The molecular mechanisms underlying the relationship between fatty liver and G6Pase-alpha have not been evaluated in humans.

Methods: Twenty-seven patients (11 men, 16 women) underwent liver biopsy. Histological diagnosis identified normal liver in 8 patients and nonalcoholic fatty liver in 19 patients. We quantified G6Pase-alpha and G6PT mRNA expression by real-time PCR with 18S as housekeeping gene. In addition, anthropometric measurements and analysis of plasma lipids and liver enzymes were performed.

Results: The groups of normal and fatty liver showed no significant differences in age, HOMA-IR, BMI, liver enzymes or waist-to-hip ratio, but total plasma cholesterol levels were higher in the fatty liver group (P<0.05). G6Pase-alpha and G6PT mRNA expressions were downregulated significantly in fatty liver compared to normal liver (P<0.05). G6Pase-alpha and G6PT mRNA expressions correlated positively (R2=0.4581, P<0.001). Both expressions did not correlate with age, BMI, liver enzymes, triglycerides or glucose levels.

Discussion: G6Pase-alpha activity is largely controlled by transcriptional levels. Our data suggest that the expression of hepatic G6Pase-alpha and G6PT are closely interlinked. The observed downregulation of G6Pase-alpha in fatty liver seems to play a major role in hepatic fat accumulation and pathogenesis of fatty liver.

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