Adipocyte Lipolysis and Acute Insulin Resistance
Ahern, Katelyn, Pharmacology - School of Medicine, University of Virginia
Harris, Thurl, MD-PHAR Pharmacology, University of Virginia
Acute hyperglycemia and systemic insulin resistance often develop after trauma, but the underlying mechanisms remain unknown. It is, however, known that surgical animal models rapidly develop adipose insulin resistance, and impaired insulin action in adipose tissue alone can result in whole body insulin resistance. Therefore, we studied the contributions of adipocyte lipolysis to the metabolic response to acute stress and the release of two signaling molecules: oxidized fatty acids (oxFA) and resistin.
To better study the potential role of oxFA, we developed a novel high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method that employed positive-ion ionization in conjunction with differential energy (DiffE) qualifier ion monitoring (QIM) to measure full-length oxidation products of linoleic acid (LA) and arachidonic acid (AA). Using this method, we demonstrated levels of oxFA increased in response to lipolysis both in vitro and in vivo. In addition, we showed that reactive oxygen species (ROS) are critical for lipolysis-dependent inhibition of the mammalian target of rapamycin (mTOR) complexes and provided preliminary data that an oxFA is responsible.
We demonstrated in vivo that resistin is released in a stress- and lipolysis-dependent manner during hemorrhagic shock (HS) and cardiovascular stress. When we further investigated this mechanism in vitro, we observed a significant, lipolysis-dependent release of resistin from adipocytes into the media. In addition, overnight pretreatment with the antioxidant EUK prevented lipolysis-dependent resistin secretion, suggesting a potential role for oxidized lipid signaling in the acute release of resistin.
PHD (Doctor of Philosophy)
resistin, oxidized fatty acid, adipocyte lipolysis, insulin resistance, acute stress
American Heart Association 17PRE33660609National Institute of Health R01DK101946National Institute of Health T32HL007284National Institute of Health 1F31DK121482-01A1