Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone.
BACKGROUND
Retinol binding protein 4 (RBP4) was recently found to be expressed and secreted by adipose tissue, and was strongly associated with insulin resistance.


OBJECTIVE
The aim was to determine the relationship between RBP4 and obesity, insulin resistance, and other markers of insulin resistance in humans.


METHODS
RBP4 mRNA levels in adipose tissue and muscle of nondiabetic human subjects with either normal or impaired glucose tolerance (IGT) were studied, along with plasma RBP4. RBP4 gene expression was also measured in adipose tissue fractions, and from visceral and sc adipose tissue (SAT) from surgical patients.


METHODS
The study was conducted at University Hospital and General Clinical Research Center.


METHODS
Insulin sensitivity (S(I)) was measured, and fat and muscle biopsies were performed. In IGT subjects, these procedures were performed before and after treatment with metformin or pioglitazone.


METHODS
The relationship between RBP4 expression and obesity, S(I), adipose tissue inflammation, and intramyocellular lipid level, and response to insulin sensitizers was measured.


RESULTS
RBP4 was expressed predominantly from the adipocyte fraction of SAT. Although SAT RBP4 expression and the plasma RBP4 level demonstrated no significant relationship with body mass index or S(I), there was a strong positive correlation between RBP4 mRNA and adipose inflammation (monocyte chemoattractant protein-1 and CD68), and glucose transporter 4 mRNA. Treatment of IGT subjects with pioglitazone resulted in an increase in S(I) and an increase in RBP4 gene expression in both adipose tissue and muscle, but not in plasma RBP4 level, and the in vitro treatment of cultured adipocytes with pioglitazone yielded a similar increase in RBP4 mRNA.


CONCLUSIONS
RBP4 gene expression in humans is associated with inflammatory markers, but not with insulin resistance. The increase in RBP4 mRNA after pioglitazone treatment is unusual, suggesting a complex regulation of this novel adipokine.
Yao-Borengasser
Aiwei
A
The Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
Varma
Vijayalakshmi
V
Bodles
Angela M
AM
Rasouli
Neda
N
Phanavanh
Bounleut
B
Lee
Mi-Jeong
MJ
Starks
Tasha
T
Kern
Leslie M
LM
Spencer
Horace J
HJ
Rashidi
Amir Adel
AA
McGehee
Robert E
RE
Fried
Susan K
SK
Kern
Philip A
PA
D000273:Adipose Tissue / Q000502:physiology; D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D002458:Cell Fractionation; D018932:Chemokine CCL2 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007333:Insulin Resistance / Q000235:genetics* / Q000276:immunology*; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology; D009765:Obesity / Q000235:genetics / Q000276:immunology; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018932:Chemokine CCL2; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D045162:Thiazolidinediones; C111835:CCL2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C101326:RBP4 protein, human; C495692:SLC2A4 protein, human