Intramyocellular lipid content and molecular adaptations in response to a 1-week high-fat diet.
OBJECTIVE
To investigate molecular adaptations that accompany the elevation of intramyocellular lipid (IMCL) content on a high-fat (HF) diet for 1 week.


METHODS
Ten subjects consumed a normal-fat (NF) diet for 1 week, followed by an HF diet for another week. After both dietary periods, we determined the IMCL content by proton magnetic resonance spectroscopy in the vastus lateralis muscle and quantified changes in gene expression, protein content, and activity in biopsy samples. We investigated genes involved in carbohydrate and fatty acid handling [lipoprotein lipase, acetyl-coenzyme A carboxylase (ACC) 2, hormone-sensitive lipase, hexokinase II, and glucose transporter 4] and measured protein levels of CD36 and phosphorylated and unphosphorylated ACC2 and the activity of adenosine monophosphate-activated kinase.


RESULTS
IMCL content was increased by 54% after the HF period. Lipoprotein lipase mRNA concentration was increased by 33%, whereas ACC2 mRNA concentration tended to be increased after the HF diet. Hexokinase II, glucose transporter 4, and hormone-sensitive lipase mRNA were unchanged after the HF diet. ACC2 and CD36 protein levels, phosphorylation status of ACC2, and adenosine monophosphate-activated kinase activity did not change in response to the HF diet.


CONCLUSIONS
We found that IMCL content in skeletal muscle increased after 1 week of HF feeding, accompanied by molecular adaptations that favor fat storage in muscle rather than oxidation.
Schrauwen-Hinderling
Vera B
VB
Department of Radiology, University Hospital Maastricht, The Netherlands. vhi@rdia.azm.nl
Kooi
Marianne Eline
ME
Hesselink
Matthijs K C
MK
Moonen-Kornips
Esther
E
Schaart
Gert
G
Mustard
Kirsty J
KJ
Hardie
D Grahame
DG
Saris
Wim H M
WH
Nicolay
Klaas
K
Schrauwen
Patrick
P
D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D005227:Fatty Acids / Q000097:blood; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D018955:CD36 Antigens; D004041:Dietary Fats; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D012333:RNA, Messenger; D014280:Triglycerides; D006593:Hexokinase; D000263:Adenylate Kinase; D002787:Sterol Esterase; D008071:Lipoprotein Lipase; D000103:Acetyl-CoA Carboxylase