GIP receptor mRNA expression in different fat tissue depots in postmenopausal non-diabetic women.
OBJECTIVE
Gastric inhibitory polypeptide (GIP) is an insulinotropic duodenal hormone released in response to meals. Recent studies in rodents suggested that GIP directly links overnutrition to obesity. Despite evidence for GIP effects on fat metabolism in humans, the GIP receptor (GIPR) has not been identified in fat tissues. We identified the GIPR gene in human subcutaneous and visceral fat tissues and tested the hypothesis that that the expression of this gene is influenced by central obesity and weight loss.


METHODS
GIPR gene mRNA expression in subcutaneous fat tissue biopsies (n=70) and in paired subcutaneous and visceral fat tissue samples (n=25) of non-diabetic postmenopausal women was studied by real-time reverse transcription polymerase chain reaction. The effect of weight reduction on GIPR gene expression in subcutaneous fat tissue was studied in a subset of 14 women.


RESULTS
GIPR adipose tissue gene expression was significantly lower in insulin resistant obese non-diabetic women (p=0.004). The GIPR mRNA expression was higher in the visceral fat tissue compared with subcutaneous fat (p<0.001). Despite adjustment for obesity-associated variables, waist circumference was the most significant predictor of GIPR gene expression in subcutaneous fat depot (F=4.066; beta=-0.997; p=0.0001) and, together with fasting insulin levels, in visceral fat (F=3.553; beta=-0.507 and beta=0.495; p=0.0001). Moderate weight reduction did not change gene expression levels of the GIPR gene (p=0.085).


CONCLUSIONS
Decreased expression of the GIPR gene in subcutaneous fat tissue is associated with signs of insulin resistance in non-diabetic women with central obesity and demonstrates that fasting hyperinsulinemia is a possible negative regulator of GIPR gene expression in subcutaneous fat. Higher GIPR gene expression levels in visceral fat vs. subcutaneous fat reflect regional differences in adipose tissue biology. Moderate weight reduction did not change gene expression levels of GIPR in subcutaneous fat.
Rudovich
Natalia
N
Department of Endocrinology, Diabetes and Nutrition, Campus B. Franklin, Charite Medicine University of Berlin, Germany. rudovich@mail.dife.de
Kaiser
Simone
S
Engeli
Stefan
S
Osterhoff
Martin
M
Gögebakan
Ozlem
O
Bluher
Matthias
M
Pfeiffer
Andreas F H
AF
D050153:Abdominal Fat / Q000378:metabolism; D052436:Adipose Tissue, White / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000378:metabolism; D014018:Tissue Distribution; D015431:Weight Loss / Q000235:genetics
D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor