Chemerin is expressed mainly in pancreas and liver, is regulated by energy deprivation, and lacks day/night variation in humans

Abstract

Objective: Chemerin is an adipocyte-secreted hormone and has recently been associated with obesity and the metabolic syndrome. Although studies in rodents have outlined the aspects of chemerin's function and expression, its physiology and expression patterns are still to be elucidated in humans.

Methods: To evaluate for any day/night variation in chemerin secretion, we analyzed hourly serum samples from six females in the fed state. To examine whether energy deprivation affects chemerin levels, and whether this could be mediated through leptin, we analyzed samples from the same subjects in the fasting state while administering either placebo or leptin. To evaluate for any potential dose-effect relationship between leptin and chemerin, we administered increasing metreleptin doses to five females. A tissue array was used to study the expression of chemerin in different human tissues. Ex vivo treatment of human fat explants from three subjects with leptin was carried out to evaluate for any direct effect of leptin on adipocyte chemerin secretion.

Results: Chemerin does not display a day/night variation, while acute energy deprivation resulted in a significant drop in circulating chemerin levels by ∼42%. The latter was unaltered by metreleptin administration, and leptin administration did not affect the secretion of chemerin by human adipose tissue studied ex vivo. Chemerin was expressed primarily in the pancreas and liver. Chemerin receptor showed increased expression in the lymph nodes and the spleen.

Conclusions: We outline for the first time chemerin expression and physiology in humans, which are different from those in mice.

Figure 1. Tissue mRNA Expression of Chemerin and CMKLR1

Relative mRNA expression of Chemerin (A) and CMKLR1 (B) in human tissues utilizing Human mRNA Tissue Array. Specific tissue type for each corresponding bar is labeled in the x-axis of each graph and a legend to group tissues by function in relation to both graphs A and B is located at the bottom of the figure. Methods of experiment are described in detail in Experimental Procedures section.

Figure 2. Day/Night Variation of Chemerin

Average 24-hour (A) chemerin (ng/ml) with no constrains, (B) chemerin (ng/ml) with 24-hour fixed period, (C) sTNFRII (pg/ml) and (D) leptin (ng/ml) levels (non-linear adjusted R² is displayed on top center of each panel). Error bars represent SD, continuous line represents 95% confidence band, and dashed line represents 95% prediction bands. Adj-R^2, Adjusted coefficient of determination.

Figure 3. Effects of Acute Energy Deprivation

Average 24-hour (A) chemerin (ng/ml), (B) sTNFRII (pg/ml), and (C) Leptin (ng/ml) levels of fed state (■), fasting with placebo administration (□), and fasting with metreleptin administration (▲). P-values are shown next to brackets.

Figure 4. Leptin Effects on Chemerin

Average 16-hour (A) chemerin (ng/mL) levels after treatment with three doses of leptin (0.01, 0.1, and 0.3 mg/Kg). Chemerin levels in supernatant (B) with () or without (■)100 ng/mL leptin treatment for 20 hours in subcutaneous and omental adipose tissue. Chemerin protein expression (C – D) in subcutaneous adipose tissue after leptin treatment. (B–D) Results are the mean of 3 experiments. Data were analyzed by paired T-Test. Values are means +/− SD.