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UCP1 inhibition in Cidea-overexpressing mice is physiologically counteracted by brown adipose tissue hyperrecruitment.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2017 Jan 01; Vol. 312 (1), pp. E72-E87. Date of Electronic Publication: 2016 Dec 06. - Publication Year :
- 2017
-
Abstract
- Cidea is a gene highly expressed in thermogenesis-competent (UCP1-containing) adipose cells, both brown and brite/beige. Here, we initially demonstrate a remarkable adipose-depot specific regulation of Cidea expression. In classical brown fat, Cidea mRNA is expressed continuously and invariably, irrespective of tissue recruitment. However, Cidea protein levels are regulated posttranscriptionally, being conspicuously induced in the thermogenically recruited state. In contrast, in brite fat, Cidea protein levels are regulated at the transcriptional level, and Cidea mRNA and protein levels are proportional to tissue "briteness." Although routinely followed as a thermogenic molecular marker, Cidea function is not clarified. Here, we employed a gain-of-function approach to examine a possible role of Cidea in the regulation of thermogenesis. We utilized transgenic aP2-hCidea mice that overexpress human Cidea in all adipose tissues. We demonstrate that UCP1 activity is markedly suppressed in brown-fat mitochondria isolated from aP2-hCidea mice. However, mitochondrial UCP1 protein levels were identical in wild-type and transgenic mice. This implies a regulatory effect of Cidea on UCP1 activity, but as we demonstrate that Cidea itself is not localized to mitochondria, we propose an indirect inhibitory effect. The Cidea-induced inhibition of UCP1 activity (observed in isolated mitochondria) is physiologically relevant since the mice, through an appropriate homeostatic compensatory mechanism, increased the total amount of UCP1 in the tissue to exactly match the diminished thermogenic capacity of the UCP1 protein and retain unaltered nonshivering thermogenic capacity. Thus, we verified Cidea as being a marker of thermogenesis-competent adipose tissues, but we conclude that Cidea, unexpectedly, functions molecularly as an indirect inhibitor of thermogenesis.<br /> (Copyright © 2017 the American Physiological Society.)
- Subjects :
- Adipose Tissue, Brown pathology
Adipose Tissue, White pathology
Animals
Apoptosis Regulatory Proteins metabolism
Blotting, Western
Calorimetry, Indirect
Cold Temperature
Humans
Mice
Mice, Transgenic
Oxygen Consumption
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Uncoupling Protein 1 metabolism
Adipose Tissue, Brown metabolism
Apoptosis Regulatory Proteins genetics
Mitochondria metabolism
RNA, Messenger metabolism
Thermogenesis genetics
Uncoupling Protein 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 312
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 27923808
- Full Text :
- https://doi.org/10.1152/ajpendo.00284.2016