Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 302

COx2, and subsequently prostaglandin PGE2. It thus reduces inflammation. Intra-
venous Apn injection, either shortly before or after the induction of ischemia in mice
reduces ischemic injury [ 583 ].

6.2.3.2 Leptin

Leptin 49 (Vol. 2 - Chaps. 1. Remote Control Cells and 3. Growth Factors and
Vol. 3 - Chap. 6. Receptors) is synthesized not only by adipocytes, but also by
cardiomyocytes. Leptin production by cultured neonatal rat ventriculomyocytes
increases upon stimulation by endothelin-1 and angiotensin-2 [ 584 ].
Leptin binds to its receptor (LR, a.k.a. OBR and LEPR) that is expressed as
splice variants classified as short (LRa, LRc-LRd, and LRf), secreted (LRe), and
long (LRb). Leptin receptors abound on the cardiomyocyte surface. The intracellular
domain of LRb primes the JaK2-STAT3 axis. Leptin activates the RhoA-RoCK and
PI3K-PKB pathways, as well as ERK1, ERK2, P38MAPK, and PKC [ 584 ].
Leptin modulates myocardial metabolism. It operates diversely according to the
cell type on fatty acid oxidation and glucose uptake [ 584 ]. 50 Leptin could also limit
lipotoxicity that occurs when fatty acid uptake exceeds oxidative capacity. Leptin
has negative inotropic effect via nitric oxide. Leptin is a predictor of poor outcome
in patients with coronary heart disease or heart failure [ 584 ]. Leptin induces cardiac
hypertrophy via the RhoA-P38MAPK pathway.

6.2.3.3 Resistin, Apelin, Visfatin, and Other Adipokines

Apelin binds to G-protein-coupled APJ receptor and exerts a positive inotropic
effect in both normal and failing myocardium via protein kinase-C and Na + -H +
exchangers [ 584 ]. Apelin exerts a cardioprotection against ischemia-reperfusion
injury.
Resistin is produced almost exclusively in white adipose tissue. It circulates
as a trimer (monomeric form of resistin) or hexamer (dimeric form). Resistin
is associated with insulin resistance. The dimerized form of resistin is more
effective in antagonizing insulin-stimulated glucose uptake in adult murine car-
diomyocytes [ 584 ].

49 Circulating leptin concentration is related to body mass and adiposity. Leptin plasma level ranges
from 5 to 15 ng/ml in non-obese individuals to reach more than 100 ng/ml in obese subjects. Leptin
is convected by blood mainly bound to plasma proteins, whereas it flows primarily in free form in
obesity.
50 Fatty acid oxidation accounts for about 70% of ATP generated under normoxic conditions,
whereas carbohydrates become the major substrate in anaerobic conditions.