A unique mechanism of desensitization to lipolysis mediated by β3- adrenoceptor in rats with thermal injury

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Abstract

Thermal injury causes a hypermetabolic state associated with increased levels of catabolic hormones, but the molecular bases for the metabolic abnormalities are poorly understood. We investigated the lipolytic responses after β3-adrenoceptor (β3-AR) agonists and evaluated the associated changes in β-AR and its downstream signaling molecules in adipocytes isolated from rats with thermal injury. Maximal lipolytic responses to a specific β3-AR agonist, BRL-37344, were significantly attenuated at post burn days (PBD) 3 and 7. Despite significant reduction of the cell surface β3-AR number and its mRNA at PBD 3 and 7, BRL-37344 and forskolin- stimulated cAMP levels were not decreased. Glycerol production in response to dibutyryl cAMP, a direct stimulant of hormone-sensitive lipase (HSL) via protein kinase A (PKA), was significantly attenuated. Although immunoblot analysis indicated no differences in the expression and activity of PKA or in the expression of HSL, HSL activity showed significant reductions. Finally, β3-AR-induced insulin secretion was indeed attenuated in vivo. These studies indicate that the β3-AR system is desensitized after burns, both in the adipocytes and in β3-AR-induced secretion of insulin. Furthermore, these data suggest a complex and unique mechanism underlying the altered signaling of lipolysis at the level of HSL in animals after burns.

Original languageEnglish (US)
Pages (from-to)E316-E324
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume277
Issue number2 40-2
DOIs
StatePublished - Aug 1999

Keywords

  • Adrenergic receptor
  • Burns
  • Hormone-sensitive lipase
  • Insulin
  • Protein kinase A

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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