PDE4 responsiveness to excess norepinephrine in obesity is blunted

[Kofi]

I guess, analogous to insulin resistance, we can term this "sympathetic
resistance."

Can J Physiol Pharmacol. 2009 Mar;87(3):196-202.
�
Reduced in vivo phosphodiesterase-4 response to acute noradrenaline
challenge in diet-induced obese rats.
Greene M, Thackeray JT, Kenk M, Thorn SL, Bevilacqua L, Harper ME,
Beanlands RS, Dasilva JN.
National Cardiac PET Centre, Division of Cardiology, University of
Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada; and
Department of Cellular and Molecular Medicine, University of Ottawa,
Ottawa, Ontario, Canada.

Altered sympathetic nervous activity has been linked to the development
and persistence of obesity, partly relating to overfeeding. Binding of
the selective, positron-emitting phosphodiesterase-4 (PDE4) inhibitor
(R)-[11C]rolipram provides a direct index of the cAMP-hydrolyzing enzyme
PDE4. This study examines progressive alterations in PDE4 in a
high-fat-fed obese animal model. (R)-[11C]Rolipram was injected into
diet-induced obese (DIO) and diet-resistant (DR) rats; the animals were
killed after 45 min, tissues were extracted, and radioactivity was
quantified. Responsiveness of PDE4 to acute noradrenaline (NA)
stimulation was determined by 3 h pretreatment with the NA reuptake
inhibitor desipramine. There was minimal variance in caloric intake,
weight gain, fasting glucose, insulin, and energy expenditure (indirect
calorimetry) measures. Basal (R)-[11C]rolipram binding was comparable
between DIO and DR rats at 2 or 8 weeks of feeding. The normal increase
of PDE4 levels in response to elevated NA by desipramine pretreatment
was ablated in PDE4-rich tissues, including brain, heart, and skeletal
muscle, of DIO animals after 8 weeks of high-fat diet. Lean DR rats
maintained PDE4 responsiveness indicative of a normal NA signal
transduction.
Publication Types:
* Research Support, Non-U.S. Gov't

PMID: 19295660