View : 32 Download: 6

Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak(-/-) Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure

Title
Obesity Resistance and Enhanced Insulin Sensitivity in Ahnak(-/-) Mice Fed a High Fat Diet Are Related to Impaired Adipogenesis and Increased Energy Expenditure
Authors
Shin, Jae HoonKim, Il YongKim, Yo NaShin, Sun MeeRoh, Kyung JinLee, Seo HyunSohn, MiraCho, Soo YoungLee, Sang HyukKo, Chang-YongKim, Han-SungChoi, Cheol SooBae, Yun SooSeong, Je Kyung
Ewha Authors
이상혁배윤수
SCOPUS Author ID
이상혁scopus; 배윤수scopus
Issue Date
2015
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 10, no. 10
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS
Abstract
Objective Recent evidence has suggested that AHNAK expression is altered in obesity, although its role in adipose tissue development remains unclear. The objective of this study was to determine the molecular mechanism by which Ahnak influences adipogenesis and glucose homeostasis. Design We investigated the in vitro role of AHNAK in adipogenesis using adipose-derived mesenchymal stem cells (ADSCs) and C3H10T1/2 cells. AHNAK-KO male mice were fed a high-fat diet (HFD; 60% calories from fat) and examined for glucose and insulin tolerances, for body fat compositions, and by hyperinsulinemic-euglycemic clamping. Energy expenditures were assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in white or brown adipose tissues. Results Adipogenesis in ADSCs was impaired in AHNAK-KO mice. The loss of AHNAK led to decreased BMP4/SMAD1 signaling, resulting in the downregulation of key regulators of adipocyte differentiation (P<0.05). AHNAK directly interacted with SMAD1 on the Ppar gamma 2 promoter. Concomitantly, HFD-fed AHNAK-KO mice displayed reduced hepatosteatosis and improved metabolic profiles, including improved glucose tolerance (P<0.001), enhanced insulin sensitivity (P<0.001), and increased energy expenditure (P<0.05), without undergoing alterations in food intake and physical activity. Conclusion AHNAK plays a crucial role in body fat accumulation by regulating adipose tissue development via interaction with the SMAD1 protein and can be involved in metabolic homeostasis.
DOI
10.1371/journal.pone.0139720
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
Files in This Item:
001.pdf(344.01 kB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE