Ire1a in pomc neurons is required for thermogenesis and glycemia

Ting Yao, Zhuo Deng, Yong Gao, Jia Sun, Xingxing Kong, Yiru Huang, Zhenyan He, Yanchao Xu, Yongsheng Chang, Kai Jiang Yu, Brianna G. Findley, Eric D. Berglund, Rui Tao Wang, Hongbo Guo, Hong Chen, Xu Li, Randal J. Kaufman, Jianqun Yan, Tiemin Liu, Kevin W. Williams

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Whether neuronal inositol-requiring enzyme 1 (Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that proopiomelanocortin (Pomc)-specific deficiency of Ire1a accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as "beiging" of white adipose tissue. We also demonstrate that loss of Ire1a in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of Ire1a in Pomc neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed Pomc neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that Ire1a-Xbp1s and associated molecular targets link ER stress in arcuate Pomc neurons to aspects of normal energy and glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)663-673
Number of pages11
JournalDiabetes
Volume66
Issue number3
DOIs
StatePublished - Mar 1 2017

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Pro-Opiomelanocortin
Thermogenesis
Neurons
Endoplasmic Reticulum Stress
Glucose
Insulin Resistance
Homeostasis
Diet
White Adipose Tissue
Inositol
Leptin
Energy Metabolism
Obesity
Insulin
Phenotype
Liver
Enzymes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Yao, T., Deng, Z., Gao, Y., Sun, J., Kong, X., Huang, Y., ... Williams, K. W. (2017). Ire1a in pomc neurons is required for thermogenesis and glycemia. Diabetes, 66(3), 663-673. https://doi.org/10.2337/db16-0533

Ire1a in pomc neurons is required for thermogenesis and glycemia. / Yao, Ting; Deng, Zhuo; Gao, Yong; Sun, Jia; Kong, Xingxing; Huang, Yiru; He, Zhenyan; Xu, Yanchao; Chang, Yongsheng; Yu, Kai Jiang; Findley, Brianna G.; Berglund, Eric D.; Wang, Rui Tao; Guo, Hongbo; Chen, Hong; Li, Xu; Kaufman, Randal J.; Yan, Jianqun; Liu, Tiemin; Williams, Kevin W.

In: Diabetes, Vol. 66, No. 3, 01.03.2017, p. 663-673.

Research output: Contribution to journalArticle

Yao, T, Deng, Z, Gao, Y, Sun, J, Kong, X, Huang, Y, He, Z, Xu, Y, Chang, Y, Yu, KJ, Findley, BG, Berglund, ED, Wang, RT, Guo, H, Chen, H, Li, X, Kaufman, RJ, Yan, J, Liu, T & Williams, KW 2017, 'Ire1a in pomc neurons is required for thermogenesis and glycemia', Diabetes, vol. 66, no. 3, pp. 663-673. https://doi.org/10.2337/db16-0533
Yao T, Deng Z, Gao Y, Sun J, Kong X, Huang Y et al. Ire1a in pomc neurons is required for thermogenesis and glycemia. Diabetes. 2017 Mar 1;66(3):663-673. https://doi.org/10.2337/db16-0533
Yao, Ting ; Deng, Zhuo ; Gao, Yong ; Sun, Jia ; Kong, Xingxing ; Huang, Yiru ; He, Zhenyan ; Xu, Yanchao ; Chang, Yongsheng ; Yu, Kai Jiang ; Findley, Brianna G. ; Berglund, Eric D. ; Wang, Rui Tao ; Guo, Hongbo ; Chen, Hong ; Li, Xu ; Kaufman, Randal J. ; Yan, Jianqun ; Liu, Tiemin ; Williams, Kevin W. / Ire1a in pomc neurons is required for thermogenesis and glycemia. In: Diabetes. 2017 ; Vol. 66, No. 3. pp. 663-673.
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