Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase

Abstract

<p><a title="Learn more about Peroxisome proliferator-activated receptor" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/peroxisome-proliferator-activated-receptor"><u>Peroxisome proliferator-activated receptors</u></a> (PPARs) have been suggested as the master regulators of <a title="Learn more about Adipose tissue" href="https://www.sciencedirect.com/topics/neuroscience/adipose-tissue"><u>adipose tissue</u></a> formation. However, their role in regulating <a title="Learn more about Brown adipose tissue" href="https://www.sciencedirect.com/topics/neuroscience/brown-adipose-tissue"><u>brown fat</u></a> functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of <a title="Learn more about Peroxisome proliferator-activated receptor alpha" href="https://www.sciencedirect.com/topics/neuroscience/peroxisome-proliferator-activated-receptor-alpha"><u>PPARα</u></a>, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of <a title="Learn more about Peroxisome proliferator-activated receptor gamma" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/peroxisome-proliferator-activated-receptor-gamma"><u>PPARγ</u></a> <em><a title="Learn more about In vitro" href="https://www.sciencedirect.com/topics/neuroscience/in-vitro"><u>in vitro</u></a></em> and <em><a title="Learn more about In vivo" href="https://www.sciencedirect.com/topics/neuroscience/in-vivo"><u>in vivo</u></a></em> led to a reduced thermogenic capacity accompanied by a loss of inducibility by <a title="Learn more about Adrenergic receptor" href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/adrenergic-receptor"><u>β-adrenergic</u></a> signaling, as well as a shift from oxidative <a title="Learn more about Fatty acids" href="https://www.sciencedirect.com/topics/neuroscience/fatty-acids"><u>fatty acid</u></a> metabolism to <a title="Learn more about Glucose" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/glucose"><u>glucose</u></a> utilization. We identified <a title="Learn more about Glycerol" href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/glycerol"><u>glycerol</u></a> kinase (Gyk) as a partial mediator of PPARγ function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPARγ-mediated regulation of brown fat function and activation by β-adrenergic signaling.<br /></p>