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I had query regarding the mechanism of action of PPARs. PPAR agonists
which act on both alpha and gamma receptors (known as dual agonists)
influence lipid and blood sugar regulation respectively.
Basically, when an agonist acts on these two receptors it helps in
lowering of body triglycerides via two main mechanism.
1.Directly by acting on PPAR alpha receptors.
2.Indirectly by acting on PPAR gamma receptors- By decreasing insulin
resistance thus decreasing insulin levels which causes decrease in
My question is, considering these two pathways causing lowering of
triglycerides independent of each other, then what, if any, are the
differences relating to onset and duration of effect produced by the
above two mechanisms.
Any references or input will be appreciated.
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The following message was posted to: PharmPK
Hepatic PPAR alpha activation lower plasma triglycerides content by
reducing liver VLDL secretion and reducing VLDL-Apo CIII synthesis which
increases TG clearance from plasma. PPAR gamma activation increases
insulin sensitivity, particularly at adipose tissue level, reducing
lipolysis and improving plasma TG clearance by the increase of the
activity of the lipase responsible for fatty acid uptake into the
adipose cell. Actually, PPARgamma activation INCREASES "body"
triglycerides, or better, body fat mass.
Since both are nuclear receptors, the pharmadynamic depends on gene
expression and protein synthesis which require few hours to be
As much as I know, in rats after an oral treatment with rosiglitazone
almost 6 hours are required to have measurable effects during insulin
clamps (a very sensitive test to measure body insulin sensitivity).
Hope will help
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