Vol. 277, Issue 2, E316-E324, August 1999
A unique mechanism of desensitization to lipolysis mediated by
3-adrenoceptor in rats with
thermal injury
Tsuneya
Ikezu1,
Shingo
Yasuhara1,
James G.
Granneman2,
Fredric B.
Kraemer3,
Takashi
Okamoto1,
Ronald G.
Tompkins1, and
Jeevendra A. J.
Martyn1
1 Department of Anesthesiology
and Critical Care, Harvard Medical School and Massachusetts General
Hospital, Boston, Massachusetts 02114;
2 Department of Psychiatry, Wayne
State University School of Medicine, Detroit, Michigan 48207; and
3 Division of Endocrinology,
Gerontology and Metabolism, Stanford University Medical Center,
Stanford, California 94305
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
3-adrenoceptor
(3-AR) agonists and evaluated
the associated changes in -AR and its downstream signaling molecules
in adipocytes isolated from rats with thermal injury. Maximal lipolytic
responses to a specific 3-AR
agonist, BRL-37344, were significantly attenuated at post burn days
(PBD) 3 and 7. Despite significant reduction of the cell surface
3-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,
3-AR-induced insulin secretion
was indeed attenuated in vivo. These studies indicate that the
3-AR system is desensitized
after burns, both in the adipocytes and in
3-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.
adrenergic receptor; burns; hormone-sensitive lipase; insulin; protein kinase A
