The purpose of the HIF-1/PHD feedback loop: To limit mTOR-induced HIF-1α

Cardiac production of B-type natriuretic peptide is inversely related to the plasma level of free fatty acids in obese individuals - possible involvement of the insulin resistance -

“…BNP production is induced by pathological conditions such as left ventricular hypertrophy, myocardial ischemia and heart failure and hemodynamic and various neurohormonal factors are considered to be involved in BNP production [2][3][4][5]. Recent studies have shown that hypoxia-inducible factor HIF-1α plays a key role in the production of BNP [35,36] and that insulin is reported to induce HIF-1α [37,38]. It is therefore conceivable BNP production is reduced in the obese individuals in the presence of insulin resistance through suppression of HIF-1α.…”

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

“…In this model, elevated levels of PHDs represents an adaptive step to match the stabilized HIFs and, thus, limit the effect of the mTOR pathway on HIF-1 [53]. The involvement of the mTOR in the regulation of HIF-1 was first suggested by independent studies of the oncogene-related activation of VEGF [54][55][56][57][58].…”

“…Although most of the experimental and modeling effort to date has been centered on the in vitro HIF response to hypoxia with the HIF pathway being the sole focus, HIF is known to have important roles in normoxia and more complex physiological conditions as well [53].…”

The real face of HIF1α in the tumor process

“…[8][9][10][11] It is well known that a normoxic HIF1 accumulation can be induced by growth factor stimulation (e.g., insulin or EGF), which induces proliferation and modified cell metabolism. 5,6,12 Nevertheless, the growth factor-induced normoxic accumulation of HIF1/HIF1α is not caused by a direct response to oxygen deprivation. Rather the application of insulin can increase the local concentration of intracellular oxygen in a tumor cell.…”

“…12,[31][32][33][34][35][36][37] The fact that HIF1 is involved in mitochondrial autophagy processes and, in this case, in the regulation of mitochondrial respiration is important. 2,38 It seems that HIF1 help to reduce the amount of toxic metabolic waste products, which should have an effect on the lifespan of cells or of a whole organism too.…”