Adiponectin improves amyloid-β 31-35-induced circadian rhythm disorder in mice

Yuan Yuan; Chen Li; Shuai Guo; Cong Sun; Na Ning; Haihu Hao; Li Wang; Yunfei Bian; Huirong Liu; Xiaohui Wang

doi:10.1111/jcmm.16932

Adiponectin improves amyloid-β 31-35-induced circadian rhythm disorder in mice

J Cell Mol Med. 2021 Oct;25(20):9851-9862. doi: 10.1111/jcmm.16932. Epub 2021 Sep 15.

Authors

Yuan Yuan^{1

2}, Chen Li¹, Shuai Guo¹, Cong Sun¹, Na Ning¹, Haihu Hao³, Li Wang^{1

4}, Yunfei Bian⁵, Huirong Liu⁶, Xiaohui Wang^{1

2

4}

Affiliations

¹ Basic Medical Sciences Center, Shanxi Medical University, Taiyuan, China.
² Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Taiyuan, China.
³ Department of Orthopedics, Shanxi Bethune Hospital & Shanxi Academy of Medical Sciences, Taiyuan, China.
⁴ Department of Pathology, Shanxi Medical University, Taiyuan, China.
⁵ Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
⁶ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Abstract

Adiponectin is an adipocyte-derived hormone, which is closely associated with the development of Alzheimer's disease (AD) and has potential preventive and therapeutic significance. In the present study, we explored the relationship between adiponectin and circadian rhythm disorder in AD, the effect of adiponectin on the abnormal expression of Bmal1 mRNA/protein induced by amyloid-β protein 31-35 (Aβ31-35), and the underlying mechanism of action. We found that adiponectin-knockout mice exhibited amyloid-β deposition, circadian rhythm disorders and abnormal expression of Bmal1. Adiponectin ameliorated the abnormal expression of the Bmal1 mRNA/protein caused by Aβ31-35 by inhibiting the activity of glycogen synthase kinase 3β (GSK3β). These results suggest that adiponectin deficiency could induce circadian rhythm disorders and abnormal expression of the Bmal1 mRNA/protein, whilst exogenous administration of adiponectin may improve Aβ31-35-induced abnormal expression of Bmal1 by inhibiting the activity of GSK3β, thus providing a novel idea for the treatment of AD.

Keywords: Alzheimer's disease; Aβ31-35; Bmal1; GSK3β; adiponectin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ARNTL Transcription Factors / genetics
ARNTL Transcription Factors / metabolism
Adiponectin / genetics
Adiponectin / metabolism*
Alzheimer Disease / etiology
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Amyloid beta-Peptides / adverse effects
Amyloid beta-Peptides / metabolism*
Animals
Cell Line
Chronobiology Disorders / etiology*
Chronobiology Disorders / metabolism*
Chronobiology Disorders / pathology
Disease Models, Animal
Disease Susceptibility
Gene Expression
Glycogen Synthase Kinase 3 beta / metabolism
Male
Mice
Mice, Knockout
Peptide Fragments / adverse effects
Peptide Fragments / metabolism*
Protein Aggregation, Pathological / metabolism
Pyramidal Cells / metabolism
Pyramidal Cells / pathology

Substances

ARNTL Transcription Factors
Adiponectin
Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (31-35)
Glycogen Synthase Kinase 3 beta
Gsk3b protein, mouse