Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice

• Published in: American journal of physiology: endocrinology and metabolism Vol. 282; no. 3; pp. E703 - E713
• Main Authors: Gregoire, Francine M, Zhang, Qin, Smith, Steven J, Tong, Carmen, Ross, David, Lopez, Henry, West, David B
• Format: Journal Article
• Language: English
• Published: United States 01.03.2002
• Subjects: Animals; Apolipoproteins A - genetics; Blood Glucose - analysis; Blotting, Northern; Body Composition; Body Mass Index; Body Weight; CCAAT-Enhancer-Binding Proteins - genetics; Cholesterol, VLDL - blood; Complement Factor D; Dietary Fats - administration & dosage; DNA-Binding Proteins - genetics; Eating; Energy Intake; Fatty Liver - etiology; Female; Gene Expression; Insulin - blood; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - physiology; Lipids - blood; Liver - chemistry; Liver - metabolism; Liver - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity - etiology; Obesity - genetics; Receptors, Cytoplasmic and Nuclear - genetics; RNA, Messenger - analysis; Serine Endopeptidases - genetics; Sterol Regulatory Element Binding Protein 1; Transcription Factors - genetics; Triglycerides - blood
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00072.2001

Pfizer Global R&D, Alameda, California 94502 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 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. intercellular adhesion molecule-1 knockout mice; obesity; dyslipidemia; steatosis; microarray * These authors contributed equally.