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Review
. 2020 Feb 12;21(4):1219.
doi: 10.3390/ijms21041219.

Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases

Hyung Muk Choi  1 , Hari Madhuri Doss  1   2 , Kyoung Soo Kim  1   2
Affiliations
Review

Multifaceted Physiological Roles of Adiponectin in Inflammation and Diseases

Hyung Muk Choi et al. Int J Mol Sci. .

Abstract

Adiponectin is the richest adipokine in human plasma, and it is mainly secreted from white adipose tissue. Adiponectin circulates in blood as high-molecular, middle-molecular, and low-molecular weight isoforms. Numerous studies have demonstrated its insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects. Additionally, decreased serum levels of adiponectin is associated with chronic inflammation of metabolic disorders including Type 2 diabetes, obesity, and atherosclerosis. However, recent studies showed that adiponectin could have pro-inflammatory roles in patients with autoimmune diseases. In particular, its high serum level was positively associated with inflammation severity and pathological progression in rheumatoid arthritis, chronic kidney disease, and inflammatory bowel disease. Thus, adiponectin seems to have both pro-inflammatory and anti-inflammatory effects. This indirectly indicates that adiponectin has different physiological roles according to an isoform and effector tissue. Knowledge on the specific functions of isoforms would help develop potential anti-inflammatory therapeutics to target specific adiponectin isoforms against metabolic disorders and autoimmune diseases. This review summarizes the current roles of adiponectin in metabolic disorders and autoimmune diseases.

Keywords: adiponectin; adiponectin isoform; anti-inflammatory; chronic kidney disease (CKD); inflammatory bowel disease (IBD); pro-inflammatory; rheumatoid arthritis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Domains and structure of adiponectin. The primary structure of adiponectin, which consist of 244 amino acids, has an N-terminal signal sequence, a variable region with attached O-glycoside side chains, a collagenous domain, and a C-terminal sequence of a globular domain.
Figure 2
Figure 2
A broad APPL1 domain structure and binding sites of interaction proteins. The primary structure of APPL1, which consist of 709 amino acids, has a BAR (Bin1/Amphiphysin/RVS167) domain, a PH (pleckstrin homology) domain, and a PTB (phosphotyrosine binding) domain. Broad sites of interacting proteins with APPL1 are labeled in green.
Figure 3
Figure 3
Key signaling pathways of adiponectin. Adiponectin and AdipoRs (AdipoR1 and AdipoR2) interact to activate downstream signaling pathways. Binding of adiponectin to its receptors activates adaptor protein APPL1. Activated APPL1 initiates complex signal transduction by activating PPAR-α and phosphorylating AMPK and p38-MAPK. Phospho-AMPK inhibits lipogenesis and promotes fatty acid oxidation and transport into the mitochondria by phosphorylating ACC-1. Phosphorylated eNOS stimulates nitric oxide (NO), which results in vasodilation. In addition, adiponectin shows cytoprotective effect because activation of AMPK suppresses mTOR and IKK-NF-κB-PTEN signaling. Metabolic effects of insulin are mainly controlled by PI3K-Akt signaling. As PI3K-Akt is activated, glycogen synthesis and glucose uptake increases but lipolysis is suppressed. Insulin sensitivity increases when IRS1/2 is activated by adiponectin.
Figure 4
Figure 4
Physiological roles of adiponectin in the main tissues.
Figure 5
Figure 5
Proposed model for pro-inflammatory and anti-inflammatory signaling of HMW.
See this image and copyright information in PMC

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