Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice.
The effects of high-fat feeding on the development of obesity were evaluated in intercellular adhesion molecule-1 (ICAM-1) knockout and C57BL/6J (B6) male mice fed a high-fat diet for < or =50 days. Serum and tissues were collected at baseline and after 1, 11, and 50 days on the diet. After 11 days on the diet, ICAM-1-deficient, but not B6, mice developed fatty livers and showed a significant increase in inguinal fat pad weight. At day 50, ICAM-1-deficient mice weighed less, and their adiposity index and circulating leptin levels were significantly lower than those of B6 controls. To better understand the early differential response to the diet, liver gene expression was analyzed at three time points by use of Affymetrix GeneChips. In both strains, a similar pattern of gene expression was detected in response to the high-fat diet. However, sterol regulatory element-binding protein-1, apolipoprotein A4, and adipsin mRNAs were significantly induced in ICAM-1-deficient livers, suggesting that these genes and their associated pathways may be involved in the acute diet response observed in the knockout mice.
Gregoire
Francine M
FM
Pfizer Global R&D, Alameda, California 94502, USA. fmgregoire@metabolex.com
Zhang
Qin
Q
Smith
Steven J
SJ
Tong
Carmen
C
Ross
David
D
Lopez
Henry
H
West
David B
DB
D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D015243:Cholesterol, VLDL / Q000097:blood; D011416:Complement Factor D; D004268:DNA-Binding Proteins / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage*; D004435:Eating; D002149:Energy Intake; D005234:Fatty Liver / Q000209:etiology; D005260:Female; D015870:Gene Expression; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D001054:Apolipoproteins A; D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; D015243:Cholesterol, VLDL; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D007328:Insulin; D008055:Lipids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; D018799:Intercellular Adhesion Molecule-1; D012697:Serine Endopeptidases; D011416:Complement Factor D; C493491:complement factor D, mouse