An intronic single base exchange leads to a brown adipose tissue-specific loss of Ucp3 expression and an altered body mass trajectory.
Uncoupling protein 3 (Ucp3) is a transport protein of the inner mitochondrial membrane and presumably is implicated in the maintenance or tolerance of high lipid oxidation rates. Ucp3 is predominantly expressed in skeletal muscle and brown adipose tissue and is regulated by a transcription factor complex involving peroxisome proliferator-activated receptor-alpha, MyoD, and COUP transcription factor II. By analysis of a mutant Djungarian hamster model lacking Ucp3 transcription specifically in brown adipose tissue, we identified a putative transcription factor-binding site that confers tissue specificity. A naturally occurring intronic point mutation disrupting this site leads to brown adipose tissue-specific loss of Ucp3 expression and an altered body weight trajectory. Our findings provide insight into tissue-specific Ucp3 regulation and, for the first time, unambiguously demonstrate that changes in Ucp3 expression can interfere with body weight regulation.
Fromme
Tobias
T
Molecular Nutritional Medicine, ZIEL Research Center for Nutrition and Food Sciences, Technische Universität München, Freising, Germany. tobias.fromme@wzw.tum.de
Hoffmann
Christoph
C
Nau
Kerstin
K
Rozman
Jan
J
Reichwald
Kathrin
K
Utting
Michael
M
Platzer
Matthias
M
Klingenspor
Martin
M
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001835:Body Weight; D006224:Cricetinae; D017931:DNA Primers; D007438:Introns; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D017931:DNA Primers; D024101:Mitochondrial Proteins; D014157:Transcription Factors