Levels of Obesity-linked Adipokines Found Altered in Cushing’s Patients

Changes in adipokine levels have been associated with obesity-related conditions

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

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People with Cushing’s syndrome have significant changes in the levels of adipokines — cell signaling molecules produced by fatty tissue — a recent study reports.

Such changes were also found to be associated with urine cortisol levels and blood adrenocorticotropic hormone (ACTH) levels, as well as several metabolic parameters.

“Defining the role of adipokines presents as a promising direction for further improvement of prevention and treatment of cardiovascular disease and diabetes in patients with [Cushing’s syndrome],” researchers wrote.

These findings were detailed in the study “Cushing’s syndrome is associated with altered adipokine profile,” which was published in the journal Frontiers in Endocrinology.

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Cushing’s syndrome is a condition that occurs when the body makes too much cortisol. In most cases, this is driven by a tumor in the brain’s pituitary gland that leads to the excessive production of ACTH, which in turn causes the adrenal glands sitting atop the kidneys to overproduce cortisol. This specific form of Cushing’s syndrome is known as Cushing’s disease.

Cushing’s syndrome is known to be linked to several metabolic disorders, including insulin resistance, diabetes, and cardiovascular complications.

Changes in adipokine levels have been linked to obesity-related conditions, including insulin resistance, type 2 diabetes, high levels of fatty molecules in the blood, and stroke. However, the role of these molecules in Cushing’s syndrome and related complications is still unclear.

Study assessed whether high cortisol in Cushing’s affects levels of 3 adipokines

A team of scientists in Poland led a study to find out whether high cortisol levels in Cushing’s patients affected the levels of three adipokines — fetuin A, fatty acid binding protein 4 (FABP4), and retinol binding protein 4 (RBP4) — and if these proteins were related to biomarkers of cardiovascular disease and diabetes.

The levels of such biomarkers, as well as those of adipokines, cortisol, and ACTH were analyzed from blood samples taken from 21 people newly diagnosed with endogenous Cushing’s syndrome and 24 healthy individuals who served as controls.

The risk of diabetes was assessed by measuring the levels of glucose (blood sugar), insulin, and glycated (sugar-bound) hemoglobin. Insulin resistance was assessed by the homeostatic model assessment for insulin resistance.

To evaluate cardiovascular risk, the researchers used the systematic coronary risk evaluation, which takes into account several factors, such as sex, age, smoking status, systolic blood pressure (the maximum pressure the heart exerts while beating), and cholesterol levels.

Defining the role of adipokines presents as a promising direction for further improvement of prevention and treatment of cardiovascular disease and diabetes in patients with [Cushing’s syndrome]

Patients with Cushing’s syndrome had lower levels of fetuin A (156.4 vs 260.7 micrograms per milliliter for the control group), as well as higher levels of FABP4 (79.8 vs. 27.9 nanograms per milliliter) and RBP4 (34 mg/L vs. 25.8).

The study also found that higher urine cortisol and blood ACTH levels correlated with lower levels of fetuin A, and higher levels of FABP4 and RBP4.

According to previous studies, fetuin A seems to prevent calcification and atherosclerosis — the buildup of fatty deposits in artery walls — which are common life-threatening complications in Cushing’s.

In fact, the study found that a decrease in fetuin A levels was associated with lower concentrations of low-density lipoprotein cholesterol (also called “bad cholesterol”), as well as higher glycated-hemoglobin levels, and an increased cardiovascular risk.

However, the team noted it is still unclear “whether low fetuin A in the course of [Cushing’s syndrome] … contributes to increased coronary artery calcification and consequently cardiovascular mortality.”

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Levels of FABP4 and RBP4 found higher in Cushing’s patients

The study also showed that higher FABP4 levels were linked to a higher body mass index and greater levels of triglycerides, both measures of body fat.

Both FABP4 and RBP4 are known to induce atherosclerosis by promoting endothelial dysfunction, a condition that causes the large blood vessels on the heart’s surface to narrow.

Higher levels of RBP4 were found to be linked to increased levels of triglycerides and systolic blood pressure, “which predisposes to endothelial dysfunction as well,” the researchers wrote.

High FABP4 levels were also linked to increased levels of glycated-hemoglobin which led researchers to conclude that these adipokines “also contribute to the development of insulin resistance and diabetes.”

However, “whether adipokines may induce lipid [fat] profile abnormalities in [Cushing’s syndrome], must be further investigated,” the researchers wrote.

The team also noted that “high circulating [blood] RBP4 in [Cushing’s syndrome] may reflect patients’ metabolic state, but is unlikely to have a causative association.”