Dataset Information

Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats.

ABSTRACT: Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats. After 6 weeks of administration, mice fed a high-fat diet (HFD) exhibited a marked reduction in adiposity. AzA treatment induced expression of PPAR-? and genes required for FAO in the liver and induced the expression of PPAR-? coactivator 1-? (Ppargc1a) and uncoupling protein-1 (Ucp1) genes in brown adipose tissue (BAT). Moreover, treatment with AzA increased insulin sensitivity and ketone body levels. This led to a reduction in the respiratory quotient and an increase in the FAO rate, as indicated by indirect calorimetry. AzA treatment had similar antiobesogenic effects in HFD-fed ob/ob mice. Importantly, AzA-associated metabolic changes were completely abrogated in HFD-fed Olfr544-/- mice. To our knowledge, this is the first report to show that Olfr544 orchestrates the metabolic interplay between the liver and adipose tissue, mobilizing stored fats from adipose tissue and shifting the fuel preference to fats in the liver and BAT.

SUBMITTER: Wu C

PROVIDER: S-EPMC5663348 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats.

Wu Chunyan C Hwang Su Hyeon SH Jia Yaoyao Y Choi Joobong J Kim Yeon-Ji YJ Choi Dahee D Pathiraja Duleepa D Choi In-Geol IG Koo Seung-Hoi SH Lee Sung-Joon SJ

The Journal of clinical investigation 20171009 11

Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting th ...[more]

PMID: 28990936

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Project description:Following the suggestion that a command encoding current target location feeds the oculomotor system during interceptive saccades, we tested the involvement of the deep superior colliculus (dSC). Extracellular activity of 52 saccade-related neurons was recorded in three monkeys while they generated saccades to targets that were static or moving along the preferred axis, away from (outward) or toward (inward) a fixated target with a constant speed (20°/s). Vertical and horizontal motions were tested when possible. Movement field (MF) parameters (boundaries, preferred vector, and firing rate) were estimated after spline fitting of the relation between the average firing rate during the motor burst and saccade amplitude. During radial target motions, the inner MF boundary shifted in the motion direction for some, but not all, neurons. Likewise, for some neurons, the lower boundaries were shifted upward during upward motions and the upper boundaries downward during downward motions. No consistent change was observed during horizontal motions. For some neurons, the preferred vectors were also shifted in the motion direction for outward, upward, and "toward the midline" target motions. The shifts of boundary and preferred vector were not correlated. The burst firing rate was consistently reduced during interceptive saccades. Our study demonstrates an involvement of dSC neurons in steering the interceptive saccade. When observed, the shifts of boundary in the direction of target motion correspond to commands related to past target locations. The absence of shift in the opposite direction implies that dSC activity does not issue predictive commands related to future target location.NEW & NOTEWORTHY The deep superior colliculus is involved in steering the saccade toward the current location of a moving target. During interceptive saccades, the active population consists of a continuum of cells ranging from neurons issuing commands related to past locations of the target to neurons issuing commands related to its current location. The motor burst of collicular neurons does not contain commands related to the future location of a moving target.

Dataset Information

Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats.

Publications

Olfactory receptor 544 reduces adiposity by steering fuel preference toward fats.

Similar Datasets

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