AHNAK deficiency promotes browning and lipolysis in mice via increased responsiveness to beta-adrenergic signalling

Title
AHNAK deficiency promotes browning and lipolysis in mice via increased responsiveness to beta-adrenergic signalling
Author
최재훈
Keywords
DIET-INDUCED THERMOGENESIS; HORMONE-SENSITIVE LIPASE; WHITE ADIPOSE-TISSUE; ENERGY-EXPENDITURE; BEIGE FAT; PROTEIN-KINASE; BETA-3-ADRENERGIC RECEPTOR; ADAPTIVE THERMOGENESIS; METABOLIC SYNDROME; GENE-EXPRESSION
Issue Date
2016-03
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v. 6, Article number 23426
Abstract
In adipose tissue, agonists of the beta 3-adrenergic receptor (ADRB3) regulate lipolysis, lipid oxidation, and thermogenesis. The deficiency in the thermogenesis induced by neuroblast differentiation-associated protein AHNAK in white adipose tissue (WAT) of mice fed a high-fat diet suggests that AHNAK may stimulate energy expenditure via development of beige fat. Here, we report that AHNAK deficiency promoted browning and thermogenic gene expression in WAT but not in brown adipose tissue of mice stimulated with the ADRB3 agonist CL-316243. Consistent with the increased thermogenesis, Ahnak(-/-) mice exhibited an increase in energy expenditure, accompanied by elevated mitochondrial biogenesis in WAT depots in response to CL-316243. Additionally, AHNAK-deficient WAT contained more eosinophils and higher levels of type 2 cytokines (IL-4/IL-13) to promote browning of WAT in response to CL-316243. This was associated with enhanced sympathetic tone in the WAT via upregulation of adrb3 and tyrosine hydroxylase (TH) in response to beta-adrenergic activation. CL-316243 activated PKA signalling and enhanced lipolysis, as evidenced by increased phosphorylation of hormone-sensitive lipase and release of free glycerol in Ahnak(-/-) mice compared to wild-type mice. Overall, these findings suggest an important role of AHNAK in the regulation of thermogenesis and lipolysis in WAT via beta-adrenergic signalling.
URI
https://www.nature.com/articles/srep23426http://hdl.handle.net/20.500.11754/34459
ISSN
2045-2322
DOI
10.1038/srep23426
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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