Insulin Sensitivity: Enhances insulin-stimulated glucose uptake in adipocytes by 47–105% via Akt phosphorylation .
Lipid Metabolism: Associates with lower triglyceride levels and improved HDL function, reducing diabetes risk .
Anti-Atherogenic: Reduces vascular inflammation and inhibits atherosclerotic plaque formation .
Vasodilation: Improves endothelial function through nitric oxide (NO) synthesis .
Suppresses pro-inflammatory cytokines (TNF-α, IL-1) and NF-κB signaling .
Attenuates mitochondrial apoptosis by modulating Bax/Bcl-2 ratios and caspase-3 activity .
Clinical Correlations:
Age Group | Men (ng/mL) | Women (ng/mL) |
---|---|---|
18–29 | 433 ± 165 | 421 ± 131 |
50–82 | 562 ± 189 | 534 ± 280 |
Omentin is a glycoprotein encoded by a peptide of 313 amino acids, containing a secretory signal sequence and a fibrinogen-related domain. It represents a novel adipokine that is predominantly expressed in visceral adipose tissue . Protein sequence analysis has revealed its unique structure that enables its function as a secretory protein in the stromal vascular compartment of visceral fat . Interestingly, omentin ESTs (expressed sequence tags) were found to be more abundant in visceral adipose tissue cDNA libraries than many other well-known adipose genes, including perilipin, adiponectin, and leptin, highlighting its biological significance in this tissue compartment .
Human omentin shows a distinct depot-specific expression pattern. Northern analysis has demonstrated that omentin mRNA is predominantly expressed in visceral adipose tissue, with minimal detection in subcutaneous fat depots in both humans and rhesus monkeys . Quantitative real-time PCR analysis revealed that omentin mRNA is specifically expressed in stromal vascular cells isolated from omental adipose tissue, but not in adipocytes themselves, with more than 150-fold lower expression in subcutaneous cell fractions . This expression pattern is further confirmed by the presence of secreted omentin protein in culture medium from omental fat explants, while being absent in medium from subcutaneous fat explants . Omentin is also detectable in human serum through Western blot analysis, confirming its role as a circulating adipokine .
Omentin exerts several beneficial effects on glucose homeostasis and metabolism. Research indicates that:
Insulin sensitivity enhancement: Recombinant omentin significantly enhances insulin-stimulated glucose uptake in both subcutaneous (47% increase, n=9, P=0.003) and omental (approximately 30% increase, n=3, P<0.05) human adipocytes .
Insulin signaling regulation: Omentin increases Akt phosphorylation both in the absence and presence of insulin, suggesting a direct role in modulating insulin signaling pathways .
Appetite and food intake regulation: Studies in animal models have shown complex effects on food intake. When administered intraperitoneally for 14 days, omentin increased food intake (starting on day 10) and body weight (starting on day 12) . It appears to decrease the expression of CART and CRH genes in the hypothalamus while increasing hypothalamic L-dopa and norepinephrine levels, suggesting neuromodulatory effects .
Potential atheroprotective effects: Beyond metabolic regulation, omentin may have protective effects against cardiovascular complications, although this aspect requires further investigation .
For researchers investigating omentin, several validated methodological approaches can be employed:
Detection in tissue samples:
Northern blot analysis for detecting omentin mRNA expression in different tissue depots
Quantitative real-time PCR for precise measurement of omentin mRNA expression, particularly when comparing between different cell fractions (stromal vascular vs. adipocytes)
Immunohistochemistry to localize omentin expression within tissue sections
Detection in biological fluids:
In vitro secretion studies:
When designing experiments, researchers should consider that omentin expression is highly depot-specific and may respond differently to experimental manipulations depending on the tissue source and metabolic context.
Omentin exerts specific effects on insulin signaling pathways, primarily:
Akt phosphorylation: Recombinant omentin increases Akt phosphorylation both in the absence and presence of insulin, suggesting it enhances insulin signal transduction . This effect appears to be mediated through the PI3K/Akt pathway.
Glucose transporter dynamics: While not affecting basal glucose uptake, omentin significantly enhances insulin-stimulated glucose uptake in adipocytes, suggesting a role in GLUT4 translocation or activity regulation .
Insulin sensitivity markers: Multiple studies have found associations between omentin levels and markers of insulin sensitivity, including homeostasis model assessment of insulin resistance (HOMA-IR) .
Metabolite profiles: Omentin concentrations are associated with favorable metabolite profiles indicating lower insulin resistance. These include positive associations with several phosphatidylcholines (PCs) such as diacyl (PC aa C32:1) and alkyl-alkyl (PC ae C32:2), and negative associations with metabolite ratios like valine-to-PC ae C32:2 .
Researchers investigating these pathways should consider examining downstream components of insulin signaling beyond Akt, including AS160, GSK3, and FOXO1, to fully characterize omentin's effects on insulin action.
Gender differences in omentin expression and function represent an important consideration for research design:
Expression patterns: Multivariable regression models have demonstrated a significant effect of gender status on serum omentin-1 concentration variability .
Metabolic protection: High omentin-1 levels have been specifically observed in men with obesity and normal glucose tolerance, suggesting a gender-specific protective effect against obesity-related metabolic disorders in males . This protective effect was not observed to the same extent in the female population.
Response to metabolic dysfunction: When comparing subjects with normal glucose tolerance (NGT) versus abnormal glucose tolerance (AGT), men with AGT showed significantly lower omentin-1 levels compared to men with NGT (p=0.035) . This pattern was not consistently observed in women, suggesting gender-specific regulation of omentin in response to metabolic dysfunction.
Gender | Obesity Status | Glucose Tolerance | Omentin-1 Levels | Significance |
---|---|---|---|---|
Male | With obesity | Normal (NGT) | Higher | p=0.035* |
Male | With obesity | Abnormal (AGT) | Lower | |
Female | With obesity | Normal/Abnormal | No clear pattern | Not significant |
*p-value comparing men with NGT vs. AGT
These findings highlight the importance of gender stratification in omentin research and suggest that the metabolic effects of omentin may be modulated by sex hormones or other gender-specific factors.
Omentin demonstrates complex relationships with glucose tolerance and insulin resistance:
Inverse relationship with obesity and insulin resistance: Multiple studies have found that omentin-1 concentrations are significantly lower in patients with obesity compared to those without obesity (p=0.027) . This suggests an inverse relationship between omentin levels and insulin resistance.
Glucose tolerance association: Comparing subjects with normal glucose tolerance (NGT) versus abnormal glucose tolerance (AGT), there is a trend toward higher omentin concentrations in people with NGT compared to those with AGT . This is particularly pronounced in male subjects.
Metabolic biomarker associations: Omentin levels significantly associate with multiple metabolites related to insulin sensitivity, including amino acids, acylcarnitines, and lipids (sphingomyelins and phosphatidylcholines) . These associations remain significant even after adjusting for various confounding factors.
Mechanistic insulin-sensitizing effects: Experimental data demonstrate that omentin enhances insulin-stimulated glucose uptake in adipocytes through activation of the Akt signaling pathway , providing a direct mechanistic link between omentin and glucose homeostasis.
Potential protective role: Research suggests that omentin may protect against metabolic disorders associated with obesity, particularly in males . This protective effect appears to be mediated through enhancement of tissue insulin sensitivity.
Researchers should note that the relationship between omentin and glucose metabolism may be influenced by multiple factors including gender, adipose tissue distribution, and existing metabolic status.
Several experimental models have proven valuable for omentin research:
When selecting experimental models, researchers should consider the depot-specific nature of omentin expression and the potential influence of metabolic context on its function.
Several contradictions and knowledge gaps exist in the current understanding of omentin:
Addressing these contradictions and knowledge gaps represents a significant opportunity for researchers to advance understanding of omentin biology and its potential therapeutic applications.
Omentin-1 contains a fibrinogen-like domain, which is crucial for its biological activity . It interacts with integrin receptors αvβ3 and αvβ5, modulating macrophage function and reversing plaque vulnerability in animal models of atherosclerosis . This interaction is essential for its role in cardiovascular health, as it suppresses inflammatory cytokines expression, macrophage infiltration, and apoptosis within atherosclerotic plaques .
Omentin-1 is also involved in cardiomyocyte (CM) maturation during postnatal heart development . It facilitates CM cell cycle arrest and metabolic maturation by interacting with bone morphogenetic protein 7 (BMP7) . Deletion of omentin-1 in mice leads to heart enlargement and dysfunction in adulthood, highlighting its importance in maintaining cardiac function .
The recombinant form of omentin, tagged with a histidine (His) tag, is used in research to study its functions and interactions. The His tag allows for easy purification and detection of the protein in experimental settings. This recombinant protein is crucial for understanding the detailed mechanisms of omentin’s actions and its potential therapeutic applications.