SUN-115 Role of Olfactory Marker Protein in High-Fat, Diet-Induced Obese Models

Abstract

Obesity causes chronic diseases such as diabetes, hyperlipidemia, and stroke, which increase the mortality rate. Among the various studies on obesity, the role of the olfactory system to regulate energy homeostasis has been recently studied. Olfactory marker protein (OMP) is a cytoplasmic protein expressed primarily in mature chemosensory neurons in the main olfactory epithelium and involved in the olfactory receptor (OR)-mediated signal transduction cascade with olfactory canonical signaling components. Recently, the expression of OR-associated components including OMP has been observed in non-olfactory tissues where there are involved in monitoring extracellular ligands. In this study, we evaluated the role of OMP on development of obesity. We confirmed that non-olfactory OMP is expressed specifically in white adipose tissue, brown adipose tissue, and Liver of mice, as well as in 3T3-L1 cell line. To determine whether OMP mediates diet-induced obesity, we examined the influence of high-fat diet (HFD) on the wild type C57/BL6 mice and OMP knock-out (KO) mice. The amount of food intake was similar in both wild-type and mutants. Although there was no difference in normal chow diet fed mice, the KO mice gained less weight than wild-type mice in HFD condition. While there was no difference in lean body mass, fat mass was significantly reduced in OMP KO mice. In white adipose tissue (WAT), fat size of OMP KO mice was smaller than wild-type mice on both normal chow and HFD condition. The principal adipogenic transcription factor, PPARγ expression was significantly decreased in OMP KO mice, whereas UCP-1 and PGC-1α expression was increased than wild-type mice. Likewise, in brown adipose tissue (BAT), reduction of fat size was observed in OMP KO mice on HFD. Thermogenesis factor, UCP-1 and PGC-1α expression was up-regulated as well. In liver, it was confirmed that the formation of fatty liver due to the high fat diet was significantly reduced in the OMP KO mice. Taken together, our results suggest that loss of olfactory function increases beige localization of white fat, promotes thermogenesis through the expression of UCP-1 and PGC-1α in brown adipose tissue, and decreases the expression of lipogenesis related markers in liver tissue, resulting in decreased body fat and reduced diet-induced obesity.