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Title: Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

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. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation.more » • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.« less

Authors:
 [1];  [1]; ; ; ; ;  [1];  [2];  [3]; ; ;  [1]
  1. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan)
  2. Department of Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan)
  3. Division of Metabolism and Biosystemic Science, Asahikawa Medical University, Asahikawa, Hokkaido (Japan)
Publication Date:
OSTI Identifier:
22458550
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 465; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADIPOSE TISSUE; DIET; DNA; ENERGY CONSUMPTION; FATS; FIBROBLASTS; GLUCOSE; GROWTH FACTORS; HOMEOSTASIS; HYPERGLYCEMIA; LIPIDS; LIVER; MESSENGER-RNA; METABOLIC DISEASES; METABOLISM; MICE; PATHOGENESIS; RECEPTORS; STRESSES

Citation Formats

Yasuda-Yamahara, Mako, Kume, Shinji, Yamahara, Kosuke, Nakazawa, Jun, Chin-Kanasaki, Masami, Araki, Hisazumi, Araki, Shin-ichi, Koya, Daisuke, Haneda, Masakzu, Ugi, Satoshi, Maegawa, Hiroshi, and Uzu, Takashi. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.08.010.
Yasuda-Yamahara, Mako, Kume, Shinji, Yamahara, Kosuke, Nakazawa, Jun, Chin-Kanasaki, Masami, Araki, Hisazumi, Araki, Shin-ichi, Koya, Daisuke, Haneda, Masakzu, Ugi, Satoshi, Maegawa, Hiroshi, & Uzu, Takashi. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure. United States. https://doi.org/10.1016/J.BBRC.2015.08.010
Yasuda-Yamahara, Mako, Kume, Shinji, Yamahara, Kosuke, Nakazawa, Jun, Chin-Kanasaki, Masami, Araki, Hisazumi, Araki, Shin-ichi, Koya, Daisuke, Haneda, Masakzu, Ugi, Satoshi, Maegawa, Hiroshi, and Uzu, Takashi. 2015. "Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure". United States. https://doi.org/10.1016/J.BBRC.2015.08.010.
@article{osti_22458550,
title = {Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure},
author = {Yasuda-Yamahara, Mako and Kume, Shinji and Yamahara, Kosuke and Nakazawa, Jun and Chin-Kanasaki, Masami and Araki, Hisazumi and Araki, Shin-ichi and Koya, Daisuke and Haneda, Masakzu and Ugi, Satoshi and Maegawa, Hiroshi and Uzu, Takashi},
abstractNote = {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. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.},
doi = {10.1016/J.BBRC.2015.08.010},
url = {https://www.osti.gov/biblio/22458550}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 465,
place = {United States},
year = {Fri Sep 18 00:00:00 EDT 2015},
month = {Fri Sep 18 00:00:00 EDT 2015}
}