Omentin

Omentin (specifically Omentin-1) is an exercise-induced adipokine that is primarily expressed in and secreted by visceral adipose tissue into the circulation PMID 40210118PMID 37730552.

• Anti-inflammatory Action: Omentin exerts potent anti-inflammatory effects by decreasing the expression of pro-inflammatory cytokines such as IL-6 and TNF-α and inhibiting the activation of the NF-κB signaling pathway PMID 37730552PMID 38786764.
• Vascular Protection: It suppresses monocyte adhesion to TNF-α-activated endothelial cells by inhibiting the expression of adhesion molecules like ICAM-1 and VCAM-1 via the PI3K-AKT signaling pathway PMID 37730552.
• Metabolic and Mitochondrial Regulation: It serves as a positive regulator of mitochondrial biogenesis by activating the AMPK-PGC1α pathway PMID 38786764.

From PMID 40210118: Omentin is expressed in visceral adipose tissue, and exercise increases Omentin levels in vivo [43]. The overexpression of Omentin in adipose tissue has been demonstrated to reduce the area affected by myocardial infarction and inhibit cardiomyocyte apoptosis [44]. Omentin mitigates high glucose-induced vascular endothelial dysfunction by inhibiting endoplasmic reticulum stress (ERS) and oxidative stress [45]. In addition, Omentin reduces arterial calcification. It is expected to be a novel target for the treatment of cardiovascular disease

• Type 2 Diabetes (T2DM): Omentin is a promising therapeutic target for managing T2DM and metabolic syndrome, as its elevation is associated with improved glucose tolerance and reduced insulin resistance PMID 36351545PMID 38786764.
• Cardiovascular Disease: It has demonstrated potential in treating heart failure and ischemic cardiac injury by inhibiting the WNT5A/Ca2+ signaling pathway and reducing the area affected by myocardial infarction PMID 40210118. It also helps alleviate the development of vascular atherosclerosis and reduces arterial calcification PMID 40210118.
• Oncology and Cachexia: In cancer patients with cancer-associated cachexia (CAC), circulating Omentin levels are notably low PMID 37730552.
• Obesity Management: Omentin is highlighted for its role in reducing abdominal fat deposits and mitigating obesity-related vascular complications PMID 38786764PMID 37730552.

Omentin-1 has demonstrated therapeutic potential in several disease states. In heart failure with preserved ejection fraction (HFpEF), omentin-1 experimentally alleviates myocardial ischemic injury, cardiac hypertrophy, and reduces oxidative and endoplasmic reticulum stress in endothelial cells while promoting nitric oxide-mediated vasodilation. PMID 40886173 Clinically, circulating omentin-1 levels are decreased in patients with HFpEF and inversely related to inflammatory biomarkers, with levels increasing following GLP-1 receptor agonist treatment. PMID 40886173

For type 2 diabetes and vascular complications, omentin-1 treatment ameliorates endothelial dysfunction by reducing vascular superoxide production, improving nitric oxide bioavailability, and restoring the anti-contractile action of perivascular adipose tissue. PMID 33099000 It protects against high glucose-induced endothelial dysfunction through the AMPK/PPARδ signaling pathway by inhibiting endoplasmic reticulum stress and oxidative stress. PMID 32001235 Recent evidence shows omentin-1 promotes wound healing in diabetic mice by enhancing vascular endothelial cell function through the PI3K/AKT/FOXO1 pathway. PMID 41266618

In metabolic dysfunction-associated steatotic liver disease (MASLD), omentin-1 supplementation reduces TNF-α levels, endoplasmic reticulum stress, and oxidative stress in hepatocytes, likely through inhibition of NF-κB and MAPK signaling pathways. PMID 38082368 For atherosclerosis and ischemic stroke, omentin-1 exhibits anti-atherosclerotic properties and may serve as a therapeutic target, with metformin and statins shown to elevate omentin-1 levels. PMID 33607071

Adipose tissue inflammation in obesity is attenuated by omentin-1 through restoration of TXNIP/NLRP3 signaling, improving glucose tolerance and insulin sensitivity. PMID 32479684 The adipokine also demonstrates anti-inflammatory effects in macrophages by inhibiting the TLR4/MyD88/NF-κB signaling pathway. PMID 31706880

Therapeutic strategies to increase omentin-1 levels include weight loss, olive oil-rich diet, aerobic training, and treatment with atorvastatin and antidiabetic drugs (metformin, pioglitazone, and exenatide). PMID 28640441 These findings collectively support omentin-1 as a promising therapeutic target for metabolic and cardiovascular diseases. PMID 35107051PMID 22724476