Adropin: A Predictor of Heart Disease

Naturally Control Metabolism & Insulin Sensitivity

Adropin is a small peptide that is linked to metabolic homeostasis and cardiovascular function, helping regulate insulin sensitivity, weight gain, certain neurocognitive disorders, and more. R

 
 

Basics

 
 

Preptin, adropin and irisin are three co-workers in the regulation of energy homeostasis. R

Adropin is derived from the Latin roots “aduro” [to set fire to] and “pinquis” [fats or oils]. R

It was first discovered in 2008 by Kumar and his coworkers. R

Peptides secreted from peripheral organs regulate lipid metabolism in key insulin-target tissues and are important for energy homeostasis and maintaining insulin sensitivity. R

Adropin has been detected in various tissues and body fluids, such as brain, cerebellum, liver, kidney, heart, pancreas, small intestine, endothelial cells, colostrum, and foods such as cheese, whey and milk. R

Low adropin levels are associated with:

  • Weight gain R
  • Type 2 Diabetes R
  • Diabetes During Pregnancy R
  • Non-Alcoholic Fatty Liver Disease R
  • Heart Attack and severity of heart failure R R
  • Hypertension R R
  • Hyperinsulinemia R
  • Hypertriglyceridemia R
  • Dyslipidemia R
  • Obstructive Sleep Apnea R
  • Diabetic Neuropathy R
  • Reduced physical activity R
  • Severity of coronary atherosclerosis R
  • Higher homocysteine R
  • Cardiac syndrome X R
  • Stable coronary artery disease R
  • Polycystic Ovary Syndrome R
  • Low left ventricular ejection fraction R
  • Pseudoexfoliation R
  • Coronary slow flow phenomenon R
  • Pediatric obstructive sleep apnea R

Benefits

1. Protects The Heart and Vascular System

 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972533/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972533/

 

Adropin directly upregulates NOS expression, increasing cerebral blood flow. R

It prevents stress-induced hypotension, inflammation, apoptosis and stroke. R

Upregulated NOS expression by adropin may even protect the lungs. R

In studies it increases significantly right before heart failure, and correlated with its severity. R

After heart attack, there is lower serum adropinR

Patients with stablecoronaryarterydisease (SCAD) had lower serum adropin levels compared to the controls. R

There is a negative correlation between C-reactive protein (specifically hs-CRP) and adropin levels. R

2. Improves Liver Function

In animal models, adropin can improve glucose clearance, reduce fasting insulin, reverse dyslipidemia and fatty liver. R R R

Adropin also decreases insulin resistance. R

It does this by sensitizing insulin signaling pathways and altering fuel selection to favor glucose. R

3. Improves Fat and Muscle

 
 

Adropin enhances muscle signaling. R

It increases glucose utilization in muscles.. R

It also reduces muscle fatty acid oxidation (FAO) by inhibiting carnitine palmitoyltransferase-1B (CPT1B), a key enzyme that transports fatty acids into muscle mitochondria for β-oxidation. R R 

In obese mice, it reduces the creation of new fatty tissue. R R

4. Improves Mitochondrial Function

In high fat diets, mitochondria can become overloaded with fatty acids, thus slowing down mitochondrial activity. R

Adropin was able to reverse this increasing glucose oxidation and reduce fatty acid oxidation (increasing CoA/acetyl-CoA ratio). R

Carnitine can also do this. R

5. Protects and Grows The Brain

 
 

Infarct size is positively correlated with blood adropin level in animal models of cerebral ischemia (stroke). R

Activation of Akt by adropin can prevent neuronal and cellular death and might contribute to neuroprotective effect of ischemic postconditioning. R

Cluster of Differentiation 36 (CD36) is known to be one of the underlying causes of cerebrovascular and neurodegenerative diseasesR

Adropin downregulates CD36 gene expressionR

Adropin also enhances cerebral energy metabolism by increasing PDHC, a rate-limiting enzyme in glucose oxidation. R

PDHC activity has been shown to be downregulated after stroke, possibly causing depression, lactic acidosis, and tissue energy depletion. All of those contribute to neuronal injury and neurological impairment. R

Adropin induces VEGF activationR

VEGF induces axonal outgrowth (suppressing cell death too) inducing neurogenesis. R

6. May Prevent Huntington Disease

Mutant huntingtin proteins exacerbate Huntington Disease. R

Adropin induces Akt Ser-473 phosphorylation attenuating mutant huntingtin toxicityR

This prevents the cells from death (via modulation of GSK3-beta and FOXO1). R

Keeping high levels of Akt may delay cell death by silencing huntingtin. R

7. May Prevent Parkinson's Disease

 
 

Loss of Akt in dopamine neurons are lost in the brains of Parkinson's patients. R

GDNF is also protective against this loss by phosphorlating Akt. R

Adropin improves Akt in dopaminergic neurons. R

8. May Help Schizophrenia

Schizophrenia is associated insulin receptor deficits. R

Specifically, schizophrenic patients may have disrupted insulin Akt signaling and insulin resistance. R

Adropin might be a beneficial in schizophrenia as it enhances Akt phosphorylation. R

9. May Repair The Brain In Alzheimer's Disease

In animal models of Alzheimer's, there is a decrease in Akt phosphorlyation and increase in FOXO3a levels. R

Since adropin enhances Akt phosphorylation, helps against insulin resistance, and obesity, it may prevent Alzheimer'sR

Adropin also increases Brain Derived Neurotrophic Factors (BDNF, via ERK1/2 signaling). R

CD36 expression is seen in the brain in Alzheimer's patients. R

Adropin reduces CD36 expression. R

10. May Help Treat Bipolar Disorder

 
 

In mood disorders, regulation of Akt/mTOR signalling is off, as well as an increase in cell-death factors, and decrease in anti-cell death factors (like BDNF). R

In a study, blood AKT1 and mTOR mRNA expression of depressive patients were lower than healthy controls. R

Akt/GSK3-beta may be important for treating mood disorders like bipolar disorder. R

11. Acts On Inflammation

Adropin may play a protective role in the body through anti-inflammatory effects. R

For example, circulating adropin level was negatively correlated with TNF-α level in women with polycystic ovarian syndrome. R

The opposite has been discussed also.

Systemic sclerosis/scleroderma (SSc) is a chronic inflammatory disease characterized by wide fibrosis of skin and internal organs. R

Serum adropin levels are higher in Scleroderma and Behçet’s Disease compared to healthy controls. R

Mechanism Of Action

 
http://journal.frontiersin.org/article/10.3389/fmolb.2016.00025/full

http://journal.frontiersin.org/article/10.3389/fmolb.2016.00025/full

 

Adropin probably effects the hypothalamic paraventricular nucleus (PVN) the most. R

Skeletal muscle is a key organ in mediating adropin's whole-body effects. R

It regulates physical activity and motor coordination via the NB-3/Notch signaling pathway. R

Adropin is found in the brain (in vascular area, pia matter, neuroglial cells, Purkinje cells, granular layer, and neurons of the central nervous system), in the glomerulus, peritubular interstitial cells, and peritubular capillary endothelial cells (kidneys), endocardium, myocardium, and epicardium (heart), sinusoidal cells (liver), and serous acini (pancreas). R

Adropin contains 76 amino acids and has a molecular weight of 4.5 kDa. R

Adropin:

  • Increases BDNF R
  • Increases NRF2 activation R
  • Increases CoA/acetyl-CoA ratio R
  • Increases phosphoglycerate and lactate R
  • Increases adiponenctin R
  • Upregulates Hes1 expression R
  • Upregulates NOS expression in both in-vivo and in-vitro R
  • Activates pyruvate dehydrogenase  R
  • Activates VEGFR2 and PI3K/Akt (thus triggering mTOR) and ERK1/2 R
  • Enhances expression of GLUT4 R
  • Reduces PDK-4 expression R
  • Inhibits carnitine palmitoyltransferase-1B R
  • Inhibits ROCK/MLC2 signaling R
  • Inhibits SIRT1 R
  • Downregulates PTEN in muscle (increasing PIP3) R R
  • Downregulates PGC-1α and CD36 R
  • Decreases TNF-a and IL-6 R
  • May affect SIRT3 R
  • Regulates FOXO1 activity R
  • Possibly inhibits PPAR-gamma?
  • Does not alter malonyl-CoA R
  • Does not alter JNK or IKK kinase R

Genetics

Adropin is encoded by the Energy Homeostasis Associated gene (gene symbol: Enho). R

Liver Enho expression is regulated by energy status and dietary nutrient content, and is altered with obesity. R

Enho mRNA is expressed in other areas of the central nervous system involved in relaying sensory information (brainstem), regulating complex behaviors (thalamus), temperature regulation (periaqueductal gray), and circadian rhythms (lateral geniculate nucleus and medial habenula). R

GPCR is an adropin receptor similar to Dopamine D2 receptors. It is found the the cerebellum, caudate, putamen, thalamus, hypothalmus, hippocampus, frontal cortex, and olfactor bulb. R

GPR151, TAAR9, GPR160, GPR19, and GPR63 are also receptors. R

Testing And Levels

Normal male subjects have serum levels of adropin around 6 ng/ml. R

Serum adropin levels do not differ between males and females, and there is also no correlation between adropin levels and age (even in children). R

Spinal cord blood adropin levels were positively correlated with gestational age and placental weight. R

Serum adropin should be utilized as a biomarker for assessing the risk of developing T2DM. R

It can help predict heart diseaseR

It can also help predict slow coronary flow. R

How To Increase/Decrease Adropin

 
 

Essentially adropin is stimulated by feeding and suppressed by fasting. R

Levels of adropin in blood correlate with carbohydrate intake. R

Higher habitual intake of carbs is associated with lower levels of adropin. R

Conversely, a higher intake of fat may be associated with higher levels of adropin. R

Increase Adropin

  • Food Intake R
  • Short Term High Fat Intake (saturated created a higher increase) R R
  • Long Term Calorie Restriction R
  • High Fiber Intake R
  • Fish Oil (Krill Oil) - DHA/EPA R
  • Fructose (in short term) R
  • Aerobic Exercise R
  • FXR agonists (like GW4064) R
  • MCT Oil/LCT oils (only effects a few when serum levels are low) R
  • Cheese R
  • Whey Protein R
  • Milk R

Decrease Adropin

  • Glucose (in short term) R
  • Hypoglycemia (reducing Enho expression) R
  • Short Term Fasting R
  • Chronic High Fat Intake R
  • Diet Induced Obesity R
  • Hypoxia (lactate may do this too) R

No Effect on Adropin

  • High Fructose Corn Syrup R
  • Sleep Restriction R

Caveats

Administration of adropin has been shown to inhibit water intake in rats. R

Adropin is also negatively correlated with body mass index (BMI) and kidney function (blood urea nitrogen, creatinine, and ACR) and positively correlated with glomerular filtration rate. R

It seems that adropin levels increase during bursts of stress and that long term higher circulation of adropin may be more beneficial than having it lower.

So adropin may be a hormetic effect on the body, but it is still unclear how the body fully adapts to it.

If you are overweight, it is probably best to increase adropin levels, but if you have scleroderma or Behçet’s, it may be best to lower your levels. 

More Research

  • Adropin improved murine limb perfusion and elevated capillary density following induction of hindlimb ischemia. R
  • Adropin attenuates components of the metabolic distress associated with obesity independently of effects on body weight or weight loss. R