Role of omentin-1 in susceptibility to anxiety and depression like behaviors

Ji，Lianru1,2,3,4; Zhang，Lang5,6; Liang，Zhi1,2,3,4; Zhong，Sufang1,2,3,4; Liu，Xiamin1,2,3,4; Liu，Zhiping9; Poon，Wai Sang7,8; Song，Yonggui2,3,4; Chen，Baodong1; Wang，Rikang1

2023-08-20

10.1016/j.mce.2023.111990

Molecular and Cellular Endocrinology   Impact Factor & Quartile

0303-7207

1872-8057

Neuro-inflammation and blood-brain barrier (BBB) dysfunction are associated with depression. Evidence shows that adipokines enter the brain from the circulation, which regulates depressive behaviors. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about its role in neuro-inflammation and mood-relevant behavior. Our results showed omentin-1 knockout mice (Omentin-1) increased susceptibility to anxiety and depressive-like behaviors, which are associated with abnormalities of cerebral blood flow (CBF) and impaired BBB permeability. Moreover, omentin-1 depletion significantly increased hippocampal pro-inflammatory cytokines (IL-1β, TNFα, IL-6), caused microglial activation, inhibited hippocampus neurogenesis, and resulted in autophagy impairment by dysregulating ATG genes. Omentin-1 deficiency also sensitized mice to the behavioral changes induced by lipopolysaccharide (LPS), suggesting that omentin-1 could rescue neuro-inflammation by acting as an anti-depressant. Our in vitro microglia cell culture data confirmed that recombinant omentin-1 suppresses microglial activation and pro-inflammatory cytokine expression induced by LPS. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of depression by providing a barrier-promoting effect and an endogenous anti-inflammatory balance to downregulate the proinflammatory cytokines.

Blood-brain barrier Depression Microglial activation Omentin-1

SCI

English

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National Natural Science Foundation of China[81803536];Peking University[KYQD202100X];Peking University[KYQD2023254];

Cell Biology ; Endocrinology & Metabolism

Cell Biology ; Endocrinology & Metabolism

WOS:001023283100001

ELSEVIER IRELAND LTD

BIOLOGY & BIOCHEMISTRY

2-s2.0-85162090068

Scopus

1.Department of Neurosurgery,Peking University Shenzhen Hospital,Shenzhen,China
2.Key Laboratory of Evaluation of Traditional Chinese Medicine Efficacy (Prevention and Treatment of Brain Disease with Mental Disorders),China
3.Key Laboratory of Depression Animal Model Based on TCM Syndrome,Jiangxi Administration of Traditional Chinese Medicine,China
4.Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Dysfunction,Jiangxi University of Chinese Medicine,China
5.Department of Pharmacy,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,China
6.The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,China
7.The University of Hong Kong,Hong Kong,China
8.Hong Kong University Shenzhen Hospital,Shen Zhen,China
9.Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,College of Pharmacy,Jinan University,Guangzhou,China

Ji，Lianru,Zhang，Lang,Liang，Zhi,et al. Role of omentin-1 in susceptibility to anxiety and depression like behaviors[J]. Molecular and Cellular Endocrinology,2023,574.

Ji，Lianru.,Zhang，Lang.,Liang，Zhi.,Zhong，Sufang.,Liu，Xiamin.,...&Wang，Rikang.(2023).Role of omentin-1 in susceptibility to anxiety and depression like behaviors.Molecular and Cellular Endocrinology,574.

Ji，Lianru,et al."Role of omentin-1 in susceptibility to anxiety and depression like behaviors".Molecular and Cellular Endocrinology 574(2023).