IL-34 is associated with obesity, chronic inflammation, and insulin resistance.
OBJECTIVE
IL-34 is a recently identified alternative ligand for colony-stimulating factor-1 (CSF-1) receptor. IL-34 and CSF-1 are regulators of differentiation, proliferation, and survival in mononuclear phagocytes. Here, we investigated the IL-34 serum concentration and expression in human adipose tissues and any associations with insulin resistance.


METHODS
We recruited 19 nondiabetic obese women, 9 type 2 diabetic women, and 27 normal-weight women. Metabolic parameters, abdominal fat distribution, serum IL-34 concentration, and IL-34 mRNA expression were measured in abdominal sc adipose tissue (SAT) and visceral adipose tissue (VAT). In addition, the expression/secretion and putative effects of IL-34 were assessed in human differentiated adipocytes. Serum IL-34 concentration was measured before and 5 to 9 months after laparoscopic Roux-en-Y gastric bypass surgery was performed on the 20 obese patients.


RESULTS
Regardless of diabetes status, obese patients demonstrated significantly higher serum IL-34 concentrations than controls. Serum IL-34 was significantly and positively correlated with insulin resistance-related metabolic parameters. IL-34 mRNA was significantly higher in VAT than SAT. IL-34 was expressed in adipocytes as well as nonadipocytes, and expression was significantly higher during adipogenesis. In differentiated adipocytes, the expression/secretion of IL-34 was enhanced by TNFα and IL-1β. In addition, IL-34 augmented fat accumulation and inhibited the stimulatory effects of insulin on glucose transport. Moreover, serum IL-34 was significantly decreased after Roux-en-Y gastric bypass-induced weight loss.


CONCLUSIONS
The present study demonstrates, for the first time, that IL-34 is expressed in human adipose tissues and the circulating concentration is significantly elevated in obese patients. This suggests that IL-34 is associated with insulin resistance.
Departments of Biomedical Sciences (E.-J.C.) and Physiology (S.K.L., Y.S.S., Y.J.J.), Cell Dysfunction Research Center, and Departments of Family Medicine (H.S.P.), Plastic Surgery (J.P.H.), and Obstetrics and Gynecology (A.R.K., D.Y.K., J.-H.K.), University of Ulsan College of Medicine, Seoul 138-736, Korea; and Departments of Family Medicine (Y.J.L.) and General Surgery (Y.-S.H.), Inha University, College of Medicine, Incheon 402-751, Korea.
Eun-Ju
EJ
Chang
Seul Ki
SK
Lee
Young Sook
YS
Song
Yeon Jin
YJ
Jang
Hye Soon
HS
Park
Joon Pio
JP
Hong
A Ra
AR
Ko
Dae Yeon
DY
Kim
Jong-Hyeok
JH
Kim
Yeon Ji
YJ
Lee
Yoon-Suk
YS
Heo
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D007378:Interleukins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000235:genetics; D055815:Young Adult
C529076:IL34 protein, human; D007378:Interleukins