| 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
|
| Resource |
| Mice |
RBRC06294 |
