Chemerin, Obesity and Diabetes

Chemerin is a chemoattractant that promotes chemotaxis in leukocyte populations that express ChemR23. Human and mouse immature mDCs and pDCs, macrophages, and NK cells respond to chemerin in ex vivo chemotaxis assays. Chemerin also stimulates the adhesion of macrophages to fibronectin and VCAM-1 through a pathway involving Gi proteins, p38, PI3K, and Akt.

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Chemerin levels increase with body mass index in humans as chemerin and its receptor, chemokine-like receptor 1, are highly expressed in adipose tissue. Adipokines have a complex but clear role in immune function.

A growing number of experiments in human subjects point toward elevated serum chemerin levels in obesity. High levels of chemerin are thought to play a key role in the development of type 2 diabetes, associated with dysregulation of the physiological processes regulated by chemerin.

The dual role played by chemerin in metabolism and inflammation may throw some light on the link between obesity and chronic inflammation, as well as disorders related to obesity such as cardiovascular disease and type 2 diabetes.

What is the link between chemerin, obesity, and diabetes?

Inflammation

Several research studies indicate that chemerin, a multifunctional peptide, can act as a regulator of adipogenesis and glucose metabolism through its interactions with chemokine-like receptor 1. Increased levels of chemerin have been linked to insulin resistance and inflammation and several studies have focused on the role of this adipokine in obesity and diabetes.

Elevated levels of chemerin and other inflammatory biomarkers indicate an inflammatory process in a high-risk obese group that suggests a pre-diabetic state. In fact, chemerin release is higher in patients with a higher body mass index, waist-to-hip ratio and fat cell volume.

Insulin resistance

Chemerin is found at significantly higher levels in the adipose tissue of obese patients compared to that of lean subjects. Higher levels of chemerin are associated with insulin resistance. Moreover, chemerin was found to activate nuclear factor-κB, p38 mitogen-activated protein kinase, and extracellular signal–regulated kinase (ERK)-1/2.

In short, adipocyte-derived secretion of chemerin can initiate a negative cross-talk between skeletal muscle and adipose tissue, worsening the risk for obesity linked to lack of insulin sensitivity.

Some in vivo studies have shown that obese diabetic sand rats have elevated levels of chemerin in the adipose tissue compared to control subjects. However, in humans, a significant difference in chemerin levels between control and diabetic patients has never been recorded, despite a correlation between chemerin and blood triglyceride level, BMI, and blood pressure.

Conclusions and perspectives

Obesity and type 2 diabetes are becoming global epidemics, and there is sufficient evidence to show that obesity is a major risk factor in the development of type 2 diabetes. But the underlying mechanism is not fully understood.

Considerable research effort is being expended on the pathophysiological relationship between diabetes mellitus and obesity. One of the factors said to contribute to this link between type 2 diabetes mellitus and obesity is altered secretion of adipokines like chemerin, which are signaling molecules derived from adipose tissues.

The link between chemerin, obesity and diabetes needs to be researched further so as to fully understand the correlating factors involved.  A better understanding of this association could improve the pharmacological management of both obese and diabetic patients.

Further Reading

• All Diabetes Content
• What is Diabetes?
• What Causes Diabetes?
• Diabetes Pathophysiology
• Diabetes Diagnosis

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.