Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1928016 | Biochemical and Biophysical Research Communications | 2015 | 7 Pages |
Abstract
Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes.
Keywords
BATFGF21HSLacyl-CoA oxidaseMnSODPPARαHFDACOIPITTUCP-1ATF4MCADIPGTTinsulin tolerance testAutophagyWAT, White adipose tissuebrown adipose tissueDiabetesUncoupling protein-1high-fat dietMedium-chain acyl-CoA dehydrogenasemanganese superoxide dismutasefibroblast growth factor 21activating transcription factor 4LAMP-2Lysosomehormone-sensitive lipaseObesityHematoxylin and Eosinlysosome-associated membrane protein 2WATCideaperoxisome proliferator-activated receptor α
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Mako Yasuda-Yamahara, Shinji Kume, Kosuke Yamahara, Jun Nakazawa, Masami Chin-Kanasaki, Hisazumi Araki, Shin-ichi Araki, Daisuke Koya, Masakzu Haneda, Satoshi Ugi, Hiroshi Maegawa, Takashi Uzu,