ICAM-1 and beta2 integrin deficiency impairs fat oxidation and insulin metabolism during fasting.
Intercellular adhesion molecule 1 (ICAM-1) and beta2 integrins play critical roles in immune responses. ICAM-1 may also participate in regulation of energy balance because ICAM-1-deficient mice become obese on a high-fat diet. We show that mice deficient in these adhesion receptors are unable to respond to fasting by up-regulation of fatty acid oxidation. Normal mice, when fasted, exhibit reduced circulating neutrophil counts and increased ICAM-1 expression and neutrophil recruitment in liver. Mice lacking ICAM-1 or beta2 integrins fail to show these responses--instead they become hypoglycemic with steatotic livers. Fasting ICAM-1-deficient mice reduce insulin more slowly than wild-type mice. This produces fasting hyperinsulinemia that prevents activation of adenosine mono-phosphate (AMP)-activated protein kinase in muscles and liver, which results in decreased import of long chain fatty acids into mitochondria. Thus, we show a new role for immune cells and their adhesion receptors in regulating metabolic response to fasting.
Babic
Aleksandar M
AM
The CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.
Wang
Hong-Wei
HW
Lai
Margaret J
MJ
Daniels
Thomas G
TG
Felbinger
Thomas W
TW
Burger
Peter C
PC
Stricker-Krongrad
Alain
A
Wagner
Denisa D
DD
D000818:Animals; D001775:Blood Circulation; D001786:Blood Glucose; D018821:CD18 Antigens / Q000378:metabolism*; D002153:Calorimetry, Indirect; D002448:Cell Adhesion; D004798:Enzymes / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction
D001786:Blood Glucose; D018821:CD18 Antigens; D004798:Enzymes; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018799:Intercellular Adhesion Molecule-1