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Review
. 2018 Jul 29:2018:4593530.
doi: 10.1155/2018/4593530. eCollection 2018.

Role of Adiponectin in Central Nervous System Disorders

Jenna Bloemer  1 , Priyanka D Pinky  1 , Manoj Govindarajulu  1 , Hao Hong  2 , Robert Judd  3 , Rajesh H Amin  1   4 , Timothy Moore  1   4 , Muralikrishnan Dhanasekaran  1   4 , Miranda N Reed  1   4 , Vishnu Suppiramaniam  1   4
Affiliations
Review

Role of Adiponectin in Central Nervous System Disorders

Jenna Bloemer et al. Neural Plast. .

Abstract

Adiponectin, the most abundant plasma adipokine, plays an important role in the regulation of glucose and lipid metabolism. Adiponectin also possesses insulin-sensitizing, anti-inflammatory, angiogenic, and vasodilatory properties which may influence central nervous system (CNS) disorders. Although initially not thought to cross the blood-brain barrier, adiponectin enters the brain through peripheral circulation. In the brain, adiponectin signaling through its receptors, AdipoR1 and AdipoR2, directly influences important brain functions such as energy homeostasis, hippocampal neurogenesis, and synaptic plasticity. Overall, based on its central and peripheral actions, recent evidence indicates that adiponectin has neuroprotective, antiatherogenic, and antidepressant effects. However, these findings are not without controversy as human observational studies report differing correlations between plasma adiponectin levels and incidence of CNS disorders. Despite these controversies, adiponectin is gaining attention as a potential therapeutic target for diverse CNS disorders, such as stroke, Alzheimer's disease, anxiety, and depression. Evidence regarding the emerging role for adiponectin in these disorders is discussed in the current review.

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Figures

Figure 1
Figure 1
Proposed beneficial effects of adiponectin in central nervous system disorders. Adiponectin receptor signaling is under investigation for central nervous system disorders including Alzheimer's disease (AD), ischemic stroke, and depression. In models of AD, adiponectin receptor activation appears to reduce amyloid beta and improve insulin sensitivity. Adiponectin receptor signaling increases angiogenesis and enhances vasodilation, which may be of benefit in the treatment or prevention of ischemic stroke. Reductions in inflammation related to adiponectin may be beneficial to decrease risk of various diseases, including ischemic stroke, AD, and depression/anxiety. Adult neurogenesis may be reduced in depression, and adiponectin promotes neurogenesis especially in response to exercise. There are a number of modifiable factors that enhance production of adiponectin and may reduce risk of the previously mentioned disorders. In particular, exercise, weight loss, a diet rich in omega-3 polyunsaturated fatty acids, and certain medications such as lipid-lowering therapies and thiazolidinediones (TZDs) all increase circulating adiponectin levels.
Figure 2
Figure 2
Proposed signaling mechanisms of adiponectin in prevention of ischemic stroke. Signaling through AdipoR1 and AdipoR2 can reduce formation of atheroma. AdipoR1 activates the AMP-activated protein kinase (AMPK) pathway resulting in phosphorylation of protein kinase B (Akt) and activation of vascular endothelial growth factor (VEGF). Activation of Akt through calcium calmodulin kinase kinase (CAMKK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and AMPK contributes to activation of endothelial nitric oxide synthase (eNOS). Additionally, AMPK and VEGF also increase eNOS activity leading to nitric oxide (NO) production. Increase in production of NO leads to vasodilation, which is beneficial in prevention of atheroma and ischemia. Adiponectin signaling reduces vascular cell adhesion molecule 1 (VCAM-1) and intracellular adhesion molecule 1 (ICAM-1), and these adhesion molecules increase atheroma size. Peroxisome proliferator-activated receptor alpha (PPARα) also reduces VCAM-1 and ICAM-1, and PPARα is activated by AdipoR2 signaling. PPARγ increases production of adiponectin and also leads to reduction of VCAM-1 and ICAM-1. This figure was produced using Servier Medical Art (http://www.servier.com/).
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