Omentin-1: a newly discovered warrior against metabolic related diseases

ABSTRACT

Introduction

Chronic metabolism-related diseases are challenging clinical problems. Omentin-1 is mainly expressed in stromal vascular cells of adipose tissue and can also be expressed in airway goblet cells, mesothelial cells, and vascular cells. Omentin-1 has been found to exert important anti-inflammatory, antioxidative and anti-apoptotic roles and to regulate endothelial dysfunction. Moreover, omentin-1 also has protective effects against cancer, atherosclerosis, type 2 diabetes mellitus, and bone metabolic diseases. The current review will discuss the therapeutic potential of omentin-1.

Areas covered

This review summarizes the biological actions of omentin-1 and provides an overview of omentin-1 in metabolic-related diseases. The relevant literature was derived from a PubMed search spanning 1998–2021 using these search terms: omentin-1, atherosclerosis, diabetes mellitus, bone, cancer, inflammation, and oxidative stress.

Expert opinion

As a novel adipocytokine, omentin-1 is a promising therapeutic target in metabolic-related diseases. Preclinical animal studies have shown encouraging results. Moreover, circulating omentin-1 has excellent potential as a noninvasive biomarker. In the future, strategies for regulating omentin-1 need to be investigated further in clinical trials in a large cohort.

KEYWORDS:

• Omentin-1
• Biological actions
• Cancer
• Type 2 diabetes mellitus
• Atherosclerosis
• Bone metabolic diseases

Abbreviations

AMPK: AMP-activated protein kinase; ASC: apoptosis-associated speck-like protein; AS: atherosclerosis; ax Spa: axial spondyloarthritis; Bcl-2:B-cell lymphoma-2; Bax: Bcl-associated x; BCG: Bacillus Calmette-Guerin; BMI; body mass index; BMD: bone mineral density; CCS, colon cancer stem cells; CRP: C-reactive protein; CAT: catalase enzymes; CVSMCs: calcifying vascular smooth muscle cells; COX-2:cyclooxygenase-2; Caspase-3: Cysteine aspartate protease-3; Caspase-1: Cysteine aspartate protease-1; DR: T2DM retinopathy; eNOS: endothelial nitric oxide synthase; ERK: extracellular regulated protein kinases; GDM: gestational diabetes mellitus; HUVECs: human umbilical vein endothelial cells; HOMA-IR: homeostasis model assessment-insulin resistance; HNF4α: hepatocyte nuclear factor 4α; HCC: hepatocellular carcinoma cells; H₂O₂: hydrogen peroxide; ICAM-1: intercellular adhesion molecule-1; IL-1α: interleukin-1α; IL-1β: interleukin-1β; IL-6: interleukin-6; IR: insulin resistance; IKK: I kappa B kinase; IMT: intima-media thickness; iNOS: inducible nitric oxide synthase; JNK: c-Jun N-terminal kinase; KLF4: Kruppel-like factor 4; Keap1: Ketch-like ECH associated protein 1; LPS: lipopolysaccharide; LDL: low-density lipoprotein; MyD88: myeloid differentiation factor 88; MSCs: mesenchymal stem cell; MDA: malondialdehyde; MCP-1: chemoattractant protein; MMP: matrix metalloproteinases; NF-κB: nuclear factor kappa-B; NO: nitric oxide; NLRP3: nucleotide binding oligomerization domain-like receptor protein 3; Nrf2: nuclear factor erythroid 2 related factor2; NDRG2: N-myc downstream regulated gene 2; NRF-1: nuclear respiratory factor 1; OGD: oxygen and glucose deprivation; OPG: osteoprotegerin; PKB/Akt: protein kinase B; PDGF-BB: platelet-derived growth factor-BB; PPAR-γ: peroxisome proliferator-activated receptor γ; PPAR-δ: peroxisome proliferator activated receptor δ; PVAT: perivascular adipose tissue; PI3K: phosphatidylinositol 3-kinase; PGE2: prostaglandin E2; ROS: reactive oxygen species; RANKL: receptor activator of nuclear factor-κB ligand; SOD: superoxide dismutase; SCF: slow coronary flow; SIRT1: silent mating type information regulation 2 homolog-1; TXNIP: thioredoxin interacting proteins; TNF-α: tumor necrosis factor-α; TLR4: toll-like receptor 4; T2DM: type 2 diabetes mellitus; TFAM: mitochondrial transcription factor A; VSMCs: vascular smooth muscle cells; VCAM-1: vascular adhesion molecule; WHR: waist-to-hip ratio.

Declaration of Interests

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Article highlights

• Omentin-1, a novel adipocytokine, is widely expressed in many cells, including endothelial cells, airway goblet cells, mesothelial cells, and vascular cells.

• Omentin-1 can exert anti-inflammatory, antioxidative, anti-apoptotic, and microbial defense effects.

• Omentin-1 reduces comorbidities associated with type 2 diabetes mellitus, such as vascular diseases and diabetic nephropathy, thereby showing a large spectrum of therapeutic potential for patients with diabetes.

• Omentin-1 is one of the most important adipocytokines for inhibiting atherosclerosis through its strong links to macrophage differentiation, inflammation, arterial calcification and plaque formation.

• Osteoblasts and osteoclasts are direct targets of omentin-1, which contributes to the clinical application of omentin-1 in bone metabolic disease prevention and treatment.

This box summarizes key points contained in the article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81660210, 81871607, and 82070422), Natural Science Foundation of Shaanxi Province (2020JM-386 and 2018JM3042), Innovation Capability Strong Foundation Plan of Xi’an City (Medical Research Project, 21YXYJ0037), and Key Research and Development Program of Shaanxi (2020ZDLSF04-03), Major Research Projects of Xi’an Science and Technology Plan (201805104YX12SF38(2)).