Telmisartan and
irbesartan are
angiotensin II receptor blockers (ARBs) and reportedly stimulate
adiponectin secretion from adipocytes via partial
peroxisome proliferator-activated receptor γ (PPARγ) activation. However, quantitative evaluation among different ARBs has not been performed.
Adiponectin exerts strong protection against a number of pathological events by suppressing cell death, inhibiting
inflammation, and enhancing cell survival, while
leptin promotes
inflammation, oxidative stress,
atherogenesis, and
thrombosis. The aim of this study was to identify the most effective ARB enhancing
adiponectin secretion without raising
leptin secretion from human white adipocytes (HWAs). Among seven ARBs (
azilsartan,
candesartan,
irbesartan,
losartan,
olmesartan,
telmisartan, and
valsartan),
telmisartan was the most effective ARB for the increase of
adiponectin secretion and
irbesartan was the second, whereas the other ARBs at 1 µM had no effect on
adiponectin secretion.
GW9662, a PPARγ antagonist, completely blocked
pioglitazone (PPARγ agonist)-induced
adiponectin secretion and
mRNA expression, whereas it unexpectedly blocked neither
telmisartan- nor
irbesartan-induced
adiponectin secretion and
mRNA expression but rather increased them.
GW6471, PPARα antagonist, and
siRNA for PPARα suppressed
telmisartan- and
irbesartan-induced
adiponectin secretion, suggesting that PPARα is the main target of these ARBs to increase
adiponectin secretion in HWAs.
Leptin secretion was not affected by any ARBs at 1 µM and
GW9662 significantly decreased the basal secretion of
leptin, suggesting that basal
leptin secretion is regulated in a PPARγ-dependent manner. We conclude that
telmisartan is the most effective ARB to increase
adiponectin secretion via PPARα without raising
leptin secretion from HWAs.