RRC ID 72134
Author Raje V, Ahern KW, Martinez BA, Howell NL, Oenarto V, Granade ME, Kim JW, Tundup S, Bottermann K, Gödecke A, Keller SR, Kadl A, Bland ML, Harris TE.
Title Adipocyte lipolysis drives acute stress-induced insulin resistance.
Journal Sci Rep
Abstract Stress hyperglycemia and insulin resistance are evolutionarily conserved metabolic adaptations to severe injury including major trauma, burns, or hemorrhagic shock (HS). In response to injury, the neuroendocrine system increases secretion of counterregulatory hormones that promote rapid mobilization of nutrient stores, impair insulin action, and ultimately cause hyperglycemia, a condition known to impair recovery from injury in the clinical setting. We investigated the contributions of adipocyte lipolysis to the metabolic response to acute stress. Both surgical injury with HS and counterregulatory hormone (epinephrine) infusion profoundly stimulated adipocyte lipolysis and simultaneously triggered insulin resistance and hyperglycemia. When lipolysis was inhibited, the stress-induced insulin resistance and hyperglycemia were largely abolished demonstrating an essential requirement for adipocyte lipolysis in promoting stress-induced insulin resistance. Interestingly, circulating non-esterified fatty acid levels did not increase with lipolysis or correlate with insulin resistance during acute stress. Instead, we show that impaired insulin sensitivity correlated with circulating levels of the adipokine resistin in a lipolysis-dependent manner. Our findings demonstrate the central importance of adipocyte lipolysis in the metabolic response to injury. This insight suggests new approaches to prevent insulin resistance and stress hyperglycemia in trauma and surgery patients and thereby improve outcomes.
Volume 10(1)
Pages 18166
Published 2020-10-23
DOI 10.1038/s41598-020-75321-0
PII 10.1038/s41598-020-75321-0
PMID 33097799
PMC PMC7584576
MeSH Adipocytes / metabolism* Animals Disease Models, Animal Epinephrine / administration & dosage Epinephrine / metabolism Female Humans Hyperglycemia / blood Hyperglycemia / etiology Hyperglycemia / metabolism* Hyperglycemia / physiopathology Insulin / metabolism Insulin Resistance / physiology Lipase / genetics Lipase / metabolism Lipolysis / physiology* Male Mice Mice, Knockout Resistin / blood Resistin / metabolism Shock, Hemorrhagic / blood Shock, Hemorrhagic / complications* Shock, Hemorrhagic / metabolism Shock, Hemorrhagic / physiopathology Surgical Wound / blood Surgical Wound / complications* Surgical Wound / metabolism Surgical Wound / physiopathology
IF 3.998
Mice RBRC06294