Downregulation of hepatic glucose-6-phosphatase-α in patients with hepatic steatosis.

Abstract

Glucose-6-phosphate transporter (G6PT) and microsomal glucose-6-phosphatase-α (G6Pase-α) perform the terminal step in glycogenolysis and gluconeogenesis. Deficiency of these proteins leads to glycogen storage diseases. Partial inhibition of G6Pase in rats results in increased hepatic triglyceride content and de novo lipogenesis leading to hepatic steatosis. Hepatic steatosis represents hepatic manifestation of the metabolic syndrome. We investigated molecular mechanisms that may explain the relationship between fatty liver and G6Pase-α in humans in detail. A total of 27 patients (11 men, 16 women) underwent liver biopsy. Histological diagnosis identified nonfatty liver in seven patients and nonalcoholic fatty liver in 20 patients. We quantified G6Pase-α and G6PT mRNA expression by real-time PCR. Anthropometric measurements and analysis of plasma lipids and liver enzymes were performed. Patients with fatty liver showed no significant differences in age, HOMA(IR) (homeostasis model assessment of insulin resistance), BMI, liver enzymes or waist-to-hip ratio compared to those with nonfatty liver, but total plasma cholesterol levels and liver fat content were higher in patients with fatty liver (P < 0.05). G6Pase-α and G6PT mRNA expressions were significantly downregulated in fatty compared to histologically normal liver (P < 0.05). G6Pase-α and G6PT mRNA expressions correlated positively (R(2) = 0.406 P < 0.05). Both expressions did not correlate with age, BMI, aspartate transaminase, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, triglycerides or glucose levels. Our data suggest that expression of hepatic G6Pase-α and G6PT are closely interlinked. Downregulation of G6Pase-α in fatty liver might be associated with hepatic fat accumulation and pathogenesis of hepatic steatosis.

• Authors: Sarah Konopelska, Tina Kienitz, Marcus Quinkler
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 19 Issue 12 Pg. 2322-6 (Dec 2011) ISSN: 1930-739X [Electronic] United States
• PMID: 21593806 (Publication Type: Journal Article)

Chemical References

• Antiporters
• Monosaccharide Transport Proteins
• RNA, Messenger
• glucose 6-phosphate(transporter)
• Cholesterol
• Glucose-6-Phosphatase

Topics

• Adipose Tissue (metabolism)
• Adult
• Antiporters (blood, genetics, metabolism)
• Biopsy
• Cholesterol (blood)
• Down-Regulation
• Fatty Liver (etiology, genetics, metabolism)
• Female
• Glucose-6-Phosphatase (genetics, metabolism)
• Humans
• Liver (metabolism)
• Male
• Middle Aged
• Monosaccharide Transport Proteins (blood, genetics, metabolism)
• Non-alcoholic Fatty Liver Disease
• Overweight (complications, genetics, metabolism)
• RNA, Messenger (metabolism)
• Real-Time Polymerase Chain Reaction