Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats

Azelaic Acid Induces Mitochondrial Biogenesis in Skeletal Muscle by Activation of Olfactory Receptor 544

“…Both wild-type and Olfr544 knockout mice were fed HFD to induce obesity and were then orally administered AzA (50 mg/kg body weight/day) for 6 weeks. Body weight and plasma glucose and triglyceride concentrations were reduced and glucose tolerance improved by AzA administration in wild-type mice but not in Olfr544 knockout mice, as reported previously (Wu et al, 2017). The mRNA expression of PGC-1α was induced by 2.0-fold in AzA soleus muscles compared with those in control mice.…”

“…Thus, we believe that Olfr544 in extra-nasal tissues such as skeletal muscle can be endogenously stimulated by AzA derived from diet or endogenous synthesis. In our previous studies, AzA levels were particularly increased in fasting state compared with those in fed state (Wu et al, 2017), thus we suggested that AzA is a redundant fasting signaling molecule that can activate Olfr544 in multiple tissue. Previously we reported that Olfr544 activation by AzA induces white adipose lipolysis, brown adipose thermogenesis, and hepatic fatty acid oxidation (Wu et al, 2017).…”

“…Healthy, male, 8-week-old ICR, and C57BL/6J mice weighing 20-25 g were purchased from Samtako (Gyeonggi-do, South Korea). Generations of Olfr544 knockout mice were generated using the CRISPR/Cas9 system to delete exon 2 (161-428 bp) of the Olfr544 gene, and the method and basic characteristics of Olfr544 knockout mice (KO) were previously published (Wu et al, 2017). Animal experiments were handled in accordance with the protocols approved by the Animal Experiment Committee of Korea University (Protocol No.…”

“…OR1A1/Olfr43 stimulated by (-)-carvone reduced hepatic steatosis through regulating the PKA-cAMP-response element binding protein (CREB)-hairy and enhancer of split-1 signaling axis (Wu et al, , 2019. The results from microarray analysis showed that Olfr544 is highly expressed in both mouse liver and white adipose tissue, and activation of Olfr544 stimulates fatty acid oxidation in hepatocytes, lipolysis and thermogenesis in white and brown adipose tissues (Wu et al, 2017), respectively. Olfr544 is also expressed in pancreatic α-cells to stimulate glucagon secretion (Kang et al, 2015).…”

“…AzA is a C9 α,ω-dicarboxylic acid (nonanedioic acid) that is found in grain foods, including oatmeal and barley (Gallagher et al, 2010), and is also endogenously produced by the peroxisomal ω-oxidation pathway as an end product of linoleic acid (Litvinov et al, 2010). AzA is a ligand for the mouse olfactory receptor Olfr544 (Kang et al, 2015;Wu et al, 2017); thus, oral administration of AzA in mice reduces adiposity, rewiring fuel preference to fats (Wu et al, 2017). Our microarray analysis of mouse skeletal muscle tissues identified Olfr544 as the most highly expressed OR.…”