GIP receptor mRNA expression in different fat tissue depots in postmenopausal non-diabetic women Natalia Rudovich a,b, ⁎ , Simone Kaiser a,b , Stefan Engeli c , Martin Osterhoff a,b , Özlem Gögebakan a,b , Matthias Bluher d , Andreas F.H. Pfeiffer a,b a Department of Endocrinology, Diabetes and Nutrition, Campus B. Franklin, Charite Medicine University of Berlin, Germany b Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam, Germany c Franz-Volhard Clinical Research Center, Charité Campus Buch, and HELIOS Clinic Berlin, Berlin, Germany d University of Leipzig, Department of Internal Medicine III, Leipzig, Germany Received 28 March 2006; received in revised form 13 February 2007; accepted 13 February 2007 Available online 23 February 2007 Abstract Aims: 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 b 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; β = - 0.997; p = 0.0001) and, together with fasting insulin levels, in visceral fat (F = 3.553; β = - 0.507 and β = 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. © 2007 Elsevier B.V. All rights reserved. Keywords: Gastric inhibitory polypeptide; GIP; GIP receptor; Insulin resistance; Central obesity 1. Introduction Gastric inhibitory polypeptide (GIP) is an insulinotropic hormone, secreted from enteroendocrine K-cells of the duodenum in response to food and nutrient absorption, which modulates glucose-dependent insulin secretion [1,2]. Another physiologically relevant role appears to be that of an anabolic agent which stimulates fat synthesis in adipocytes and glucose utilisation in muscle [3,4]. GIP increases the glucose transport into these tissues and stimulates the lipoprotein lipase activity and the conversion of free fatty acids to triglycerides in the Regulatory Peptides 142 (2007) 138 – 145 www.elsevier.com/locate/regpep Abbreviations: GIP, gastric inhibitory polypeptide; GIPR, gastric inhibitory polypeptide receptor; HOMA IR , homeostasis model assessment of insulin resistance; IRS-1, insulin receptor substrate 1; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; 18S, human ribosomal Protein 18S; SDHA, succinate dehydrogenase complex subunit A; SP, stimulatory protein. ⁎ Corresponding author. German Institute of Human Nutrition Potsdam, Arthur-Scheunert-Street 114-116, 14558 Nuthetal, Germany. Tel.: +49 33 2008 8771; fax: +49 33 2008 8777. E-mail address: rudovich@mail.dife.de (N. Rudovich). 0167-0115/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.regpep.2007.02.006