Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 301

energy supply

AMPK

+

adiponectin

TNF α

+

−

Cox2

PGE2

Fig. 6.2 Adiponectin activities. Adiponectin stimulates cyclooxygenase-2 (Cox2) and the synthe-
sis of prostaglandin-E2 (PGE2), and thereby inhibits tumor-necrosis factor TNF α . It also acts via

adenosine monophosphate-activated protein kinase (AMPK).

6.2.3.1 Adiponectin

Adiponectin 48 (Apn; Vol. 2 - Chaps. 1. Remote Control Cells and 3. Growth Factors
and Vol. 3 - Chap. 6. Receptors) produced by adipocytes has cardioprotective
effects, via its anti-inflammatory and anti-atherogenic properties (Fig. 6.2 ). Adi-
ponectin binds to adiponectin receptors AdipoR1 and AdipoR2, which also link
adaptors. Adiponectin is an insulin-sensitizing hormone, as it increases sensitivity
to insulin in muscle and liver.
The adiponectin receptors — AdipoR1 and AdipoR2 — are expressed in
the heart. Stimulated AdipoRs increases AMP-activated protein kinase, mediates
peroxisome proliferator-activated receptor- α

ligand activities, glucose uptake, and
fatty acid oxidation [ 581 ]. Low levels of circulating adiponectin, as well as AdipoR1
and -R2, are measured in obesity, which lead to insulin resistance.
In cultured neonatal rat ventriculomyocytes, insulin decreases production of
adiponectin receptor AdipoR1, but not that of AdipoR2 receptor via the PI3K-
PKB axis and FoxO1 phosphorylation and translocation from the nucleus to the
cytosol [ 582 ]. Factor FoxO1 binds to the promoter of the ADIPOR1 gene.
Adiponectin acts either via AMPK or via cyclooxygenase COx2, involved in
prostanoid synthesis (AMPK-independent pathway; Fig. 6.2 ). Kinase AMPK, which
is also activated by an increased ratio of AMP to ATP, supports fatty acid catabolism
and glucose uptake and inhibits glucose synthesis. Enzyme AMPK also protects
cardiomyocytes from ischemic injury, particularly hypoxia-reoxygenation-induced
apoptosis. Suppression of cardiac AMPK activity indeed leads to increased injury
when myocardium perfusion is reduced. Phosphorylation (activation) of AMPK
after cardiac ischemia-reperfusion injury is attenuated in hearts of adiponectin-
deficient mice [ 583 ]. Adiponectin prevents TNF

α

production by upregulating

48 Adiponectin is also called ACRP30, AdipoQ, or gelatin-binding protein-28. It is involved in
the regulation of lipid and glucose metabolism, as well as in differentiation of adipocytes. Its
plasma concentration ranges from 3 to 30 g/ml and accounts for 0.01% of total plasma protein.

Adiponectin expression and subsequent release from adipocytes are stimulated by activated
peroxisome proliferator-activated receptor PPAR