Heart-type fatty acid-binding protein is essential for efficient brown adipose tissue fatty acid oxidation and cold tolerance.
Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3(-/-) mice exhibit extreme cold sensitivity despite induction of uncoupling and oxidative genes and hydrolysis of brown adipose tissue lipid stores. However, using FABP3 gain- and loss-of-function approaches in brown adipocytes, we detected a correlation between FABP3 levels and the utilization of exogenous fatty acids. Thus, Fabp3(-/-) brown adipocytes fail to oxidize exogenously supplied fatty acids, whereas enhanced Fabp3 expression promotes more efficient oxidation. These results suggest that FABP3 levels are a determinant of fatty acid oxidation efficiency by brown adipose tissue and that FABP3 represents a potential target for modulation of energy dissipation.
Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA.
Laurent
L
Vergnes
Robert
R
Chin
Stephen G
SG
Young
Karen
K
Reue
D052437:Adipocytes, Brown / Q000378:metabolism*; D000818:Animals; D001833:Body Temperature Regulation; D002460:Cell Line; D003080:Cold Temperature; D005215:Fasting / Q000378:metabolism; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009154:Mutation; D010084:Oxidation-Reduction
C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005947:Glucose