Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructose.
Women, but not men, show an association between fructose consumption and an increased risk of Type 2 diabetes mellitus. As rats are considered a model for human fructose metabolism, we sought to determine whether such a gender-related difference is present in Sprague-Dawley rats and to analyze the molecular mechanism behind. Male and female Sprague-Dawley rats had free access to water or to a 10% w/v fructose solution for 14 days. Plasma analytes, liver triglycerides and enzyme activities and the expression of enzymes and transcription factors related to fatty acid metabolism, insulin signaling and glucose tolerance were determined. Fructose-fed rats had hypertriglyceridemia, steatosis and reduced fatty acid oxidation activity, although the metabolic pattern of fructose-fed female rats was different to that observed for male rats. Fructose-fed female, but not male rats, showed no change in plasma leptin; they had hyperinsulinemia, an altered glucose tolerance test and less liver insulin receptor substrate-2. Further, only fructose-fed female rats had increased adenosine 5'-monophosphate (AMP)-activated protein kinase activity, resulting in a decreased expression of hepatic nuclear factor 4 and sterol response element binding protein 1. These differences were related to the fact that liver expression of the enzyme fructokinase, controlling fructose metabolism, was markedly induced by fructose ingestion in female, but not in male rats, resulting in a significant increase in the AMP/adenosine 5'-triphosphate (ATP) ratio and, thus, AMP-activated protein kinase activation, in female rats only. The difference in fructokinase induction could explain the higher metabolic burden produced by fructose ingestion in the livers of female Sprague-Dawley rats.
Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, IBUB (Institute of Biomedicine University of Barcelona),and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona 08028, Spain.
Laia
L
Vilà
Núria
N
Roglans
Victoria
V
Perna
Rosa M
RM
Sánchez
Manuel
M
Vázquez-Carrera
Marta
M
Alegret
Juan C
JC
Laguna
D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D005260:Female; D005631:Fructokinases / Q000235:genetics* / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage*; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D015228:Hypertriglyceridemia / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; D020738:Leptin; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; D005632:Fructose; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D005631:Fructokinases; C046173:fructokinase; D055372:AMP-Activated Protein Kinases