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Gene expression profiling in adipose tissue of Sprague Dawley rats identifies olfactory receptor 984 as a potential obesity treatment target

Giusepponi, Maria Elena, Kern, Matthias, Chakaroun, Rima, Wohland, Tobias, Kovacs, Peter, Dietrich, Arne, Schön, Michael R., Krohn, Knut, Pucci, Mariangela, Polidori, Carlo, Micioni Di Bonaventura, Maria Vittoria, Stumvoll, Michael, Blüher, Matthias, Cifani, Carlo, Klöting, Nora
Biochemical and biophysical research communications 2018 v.505 no.3 pp. 801-806
adipocytes, adipose tissue, gender, gene expression, gene expression regulation, genes, glucose, glucose tolerance, high fat diet, homeostasis, humans, insulin, laboratory animals, messenger RNA, mice, noninsulin-dependent diabetes mellitus, obesity, olfactory receptors, phenotype, quantitative polymerase chain reaction, rats, reverse transcriptase polymerase chain reaction
The aim of the study was to identify and functionally characterize novel candidate gene/s involved in the development of resistance to diet-induced obesity in rats.In a high-fat-diet (HFD) study of rats, we found subgroups which either developed resistance to HFD-induced obesity (DR) or showed an obesity-prone phenotype (DIO). Gene expression analysis in 10 samples (5 DIO vs 5 DR) was performed. The most promising gene, OR6C3 (orthologous with rat Olr984 and mouse Olfr788) was measured by qRT-PCR in paired samples of human visceral (Vis) and subcutaneous (SC) adipose tissue (AT) (n = 225) and in sub-fractions of adipocytes and cells of stromal vascular fraction. Gene expression analyses showed Olr984 with significantly reduced mRNA expression in DR rats. In the Vis AT of human samples we found an up-regulation of OR6C3 compared to SC AT, independent of gender, glucose tolerance or type 2 diabetes. We observed significantly lower levels of SC AT OR6C3 mRNA in subjects with obesity compared to those with normal-weight or overweight. OR6C3 is more expressed in SVF than in adipocytes.Olr984 could be a novel candidate gene related to diet-induced obesity in rats. Variation in human AT mRNA expression is related to obesity parameters and glucose homeostasis and linked to the regulatory role of insulin on the Olr984.