Confocal Imaging of Them1 Localization for Improved Elucidation of Thermogenic Signaling Pathways

Overview

The prevalence of obesity has led to increased incidence of diseases including heart disease, high blood pressure and diabetes. Biologically, lipids from obesity-inducing foods are stored in brown and white adipose tissue. Brown adipose tissue (BAT) has shown to have a greater presence in the human body than previously assumed, and specifically contains a greater quantity of mitochondria and lipid droplets that participate in thermogenesis to consume the lipids. This study characterizes the lipid metabolism of thioesterase superfamily member 1 (Them1), a protein in the non-shivering thermogenic pathway. The subcellular localization of Them1 is found in two distinct states. A punctate state which is characterized by a high intensity accumulation of Them1 in a smaller region, and a diffuse state which has a lower intensity of Them1 over a larger region. This study found that Them1 is localized in a punctate state close to lipid droplets and will re-localize to a diffuse state after phosphorylation. We also characterized the adapted pathway that Them1 follows for phosphorylation: from an initial norepinephrine activation, followed by protein kinase A activation which is followed by protein kinase C activation (PKC). PKC was then found to phosphorylate the S15 site specifically on the Them1 molecule to cause diffusion. The localization of Them1 provides information about the physiological characteristics of Them1 functionality in BAT, which has therapeutic applications for lipid metabolism treatments.

Competition history

• AJAS 2018 Category not listed

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