Dual attenuation of proteasomal and autophagic BMAL1 degradation in Clock δ "19/+ mice contributes to improved glucose homeostasis

Kwon Jeong, Baokun He, Kazunari Nohara, Noheon Park, Youngmin Shin, Seonghwa Kim, Kazuhiro Shimomura, Nobuya Koike, Seung Hee Yoo, Zheng Chen

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Circadian clocks orchestrate essential physiology in response to various cues, yet their mechanistic and functional plasticity remains unclear. Here, we investigated Clock δ"19/+ heterozygous (Clk/+) mice, known to display lengthened periodicity and dampened amplitude, as a model of partially perturbed clocks. Interestingly, Clk/+ mice exhibited improved glycemic control and resistance to circadian period lengthening under high-fat diet (HFD). Furthermore, BMAL1 protein levels in Clk/+ mouse liver were upregulated compared with wild-type (WT) mice under HFD. Pharmacological and molecular studies showed that BMAL1 turnover entailed proteasomal and autophagic activities, and CLOCKδ"19 attenuated both processes. Consistent with an important role of BMAL1 in glycemic control, enhanced activation of insulin signaling was observed in Clk/+ mice relative to WT in HFD. Finally, transcriptome analysis revealed reprogramming of clock-controlled metabolic genes in Clk/+ mice. Our results demonstrate a novel role of autophagy in circadian regulation and reveal an unforeseen plasticity of circadian and metabolic networks.

Original languageEnglish (US)
Article number12801
JournalScientific Reports
Volume5
DOIs
StatePublished - Jul 31 2015

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Homeostasis
Glucose
High Fat Diet
ARNTL Transcription Factors
Circadian Clocks
Autophagy
Gene Expression Profiling
Periodicity
Metabolic Networks and Pathways
Cues
Pharmacology
Insulin
Liver
Genes

ASJC Scopus subject areas

  • General

Cite this

Dual attenuation of proteasomal and autophagic BMAL1 degradation in Clock δ "19/+ mice contributes to improved glucose homeostasis. / Jeong, Kwon; He, Baokun; Nohara, Kazunari; Park, Noheon; Shin, Youngmin; Kim, Seonghwa; Shimomura, Kazuhiro; Koike, Nobuya; Yoo, Seung Hee; Chen, Zheng.

In: Scientific Reports, Vol. 5, 12801, 31.07.2015.

Research output: Contribution to journalArticle

Jeong, K, He, B, Nohara, K, Park, N, Shin, Y, Kim, S, Shimomura, K, Koike, N, Yoo, SH & Chen, Z 2015, 'Dual attenuation of proteasomal and autophagic BMAL1 degradation in Clock δ "19/+ mice contributes to improved glucose homeostasis', Scientific Reports, vol. 5, 12801. https://doi.org/10.1038/srep12801
Jeong, Kwon ; He, Baokun ; Nohara, Kazunari ; Park, Noheon ; Shin, Youngmin ; Kim, Seonghwa ; Shimomura, Kazuhiro ; Koike, Nobuya ; Yoo, Seung Hee ; Chen, Zheng. / Dual attenuation of proteasomal and autophagic BMAL1 degradation in Clock δ "19/+ mice contributes to improved glucose homeostasis. In: Scientific Reports. 2015 ; Vol. 5.
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AU - Shin, Youngmin

AU - Kim, Seonghwa

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AU - Chen, Zheng

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