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Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation

XING XIAN YU^*,1, WEIGUANG MAO^*,1, ALAN ZHONG, PETER SCHOW, JENNIFER BRUSH, STEVEN W. SHERWOOD, SEAN H. ADAMS^* and GUOHUA PAN^*2

Departments of
^* Endocrinology,
Molecular Biology, and
Bioassay and Bioimage, Genentech, Inc., South San Francisco, California 94080, USA

²Correspondence: Department of Endocrinology, Genentech, Inc., M/S-37, 1 DNA Way, South San Francisco, CA 94080, USA. E-mail:jgpan{at}gene.com

Mitochondrial uncoupling proteins have been implicated in the maintenance of metabolic rate and adaptational thermoregulation. We recently reported the identification of a brain-specific mitochondrial uncoupling protein homologue, UCP4. Here we characterized another newly described member of the uncoupling protein family, termed UCP5 (also called BMCP1). UCP5 transcripts are present in multiple human and mouse tissues, with an especially high abundance in the brain and testis. Expression of UCP5 in mammalian cells reduces the mitochondrial membrane potential. Multiple isoforms of UCP5 were identified and exhibited tissue-specific distribution and different potency in reduction of membrane potential. Furthermore, the mRNA abundance of both UCP4 and UCP5 is modulated by nutritional status or temperature in a tissue-specific manner in mice. Brain UCP4 and UCP5 mRNA transcripts rose by 1.5- and 1.7-fold, respectively, and liver UCP5 expression increased by 1.8-fold in response to acute cold exposure. A high-fat diet increased UCP5 mRNA in liver by 1.6-fold selectively in the obesity-resistant A/J but not in the obesity-prone C57BL/6J mouse strain. Liver UCP5 expression decreased significantly with a 24 h fast and was restored to the normal level after refeeding. In contrast, brain transcripts for both genes were not significantly altered by fasting or high-fat diet. These findings are consistent with the notion that UCP4 and UCP5 may be involved in tissue-specific thermoregulation and metabolic changes associated with nutritional status.—Yu, X. X., Mao, W., Zhong, A., Schow, P., Brush, J., Sherwood, S. W., Adams, S. H., Pan, G. Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation.

Key Words: uncoupling proteins • metabolism • thermoregulation • mitochondrial membrane potential

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