EFFECTS REF
Immunostimulation MET: -
hyperinsulinemia and insulin-related pathways 24, 25
regulation of inflammatory processes
↑ energy stress, which leads to apoptosis of certain cancer cells 46, 47
↓ of the Warburg effect 24, 47, 48
inhibition of the mTORC1 pathway 47
↑ caspases 3 and 7 25
↑ Bad and Bax expression
↓ of Bcl-2 and Bcl-xl
↓ of VEGF production
↓ of cyclin D1 and E2F1 expression
↓ of fatty acid synthesis in prostate cancer cells 24, 47
anti-folate effect
↑ P53 phosphorylation and its regulator, MDMX (indicating cell cycle arrest)
↑ cell resistance of lung adenocarcinoma without LKB1 after AMPK restoration
↓ of ROS production 49
inhibition of tumor growth in obese and pre-diabetic rats
↓ of TGF-β
↓ epithelial-mesenchymal transition
regulation of the expression of Notch receptors
↓ viability of rho0 cancer cells (without mitochondrial DNA) 50
↑ DNA methylation using S-adenosyl-methionine in breast cancer cells 51
↑ sensitivity to chemotherapy in cancer stem cells 25
↑ sensitivity to radiation therapy 24
higher sensitivity of MET in cells with high Myc expression in cancer suppression 46
inhibition of M2 macrophage polarization and induction of change from M2 to M1 polarization 45
↓ the amount of myeloid suppressor cells and their migration to tumors
↓ number of Treg lymphocytes
↑ the amount of memory T lymphocytes
Immunosuppression MET: -
inhibition of monocyte differentiation into macrophages 45
↓ infiltration of monocytes or macrophages in diseased tissues
↑ anti-inflammatory T cells (like Th2, for example) or immunosuppressive (Treg, for example)
↓ inflammatory T cells (such as Th1 or Th17, for example)
↓ of inflammatory cytokine expression and ↑ of anti-inflammatory cytokines
inhibition of function and ↓ number of neutrophils , 45, 52
improvement in B lymphocyte function and ↑ antibody production 53
↓ of M1 macrophages and ↑ of M2 macrophages 45, 54
suppression of phosphatase and tensin homolog (PTEN), a tumor suppressor gene, in aortic smooth muscle cells 55
↓ expression of messenger RNA from inflammatory cytokines (TNFα, IL-1α, IL-1β and IL-6), chemokines and NF-κB 52, 55, 56
↑ in the amount of Th2 or Treg lymphocytes and ↓ in the amount and infiltration of Th1 and Th17 lymphocytes in diseased tissues 56
↓ of autoantibodies in relevant models of autoimmune diseases
↓ in the concentration of components associated with neutrophil extracellular traps (NETs) 57
Autophagy and Longevity MET: -
↑ SIRT3 levels (associated with ↑ biogenesis, mitochondrial function, ↓ senescence of cardiomyocytes, etc.) 58
↑ reverse transcriptase (hTERT) telomerase activity (associated with ↓ senescence in endothelial cells)
↓ senescence markers: p16, p21, p27 and p53
↑ the β-oxidation regulatory protein, ACAD10, associated with ↑ nematode survival 22
↑ in the expression of FGF21, a mitokine capable of improving the lipid profile, glucose uptake, etc. 59
PHEN: -
↓ autophagy 60
Mitochondrial and Associated Effects MET, PHEN: -
↓ of the activity of mitochondria complex I and, therefore, of oxidative phosphorylation 21, 49
↓ in the production of ROS by complex I 20, 21, 23, 49, 50
decrease in ROS production by SDH and mGPDH 50
MET: -
inhibition of mitochondrial glycerophosphate dehydrogenase (mGPDH) 20, 50, 61
inhibition of ATP synthase and succinate dehydrogenase (SDH) 50
activation of AMPK due to energy stress 24, 25
inhibition of acetyl-CoA-carboxylase and ↓ expression of lipogenic genes 24
↓ gluconeogenesis in hepatocytes 23-25
↓ oxidative stress and ↑ antioxidant defenses with long-term therapy 58
improvement of superoxide desmutase levels in patients with DM2 52
Cardiovascular Effects MET: -
protection against cerebral ischemia via nuclear factor related to erythroid 2 (Nrf2) or inhibition of the NF-κB cascade 62
recovery of post-stroke function and ischemia damage
improvement of angiogenesis with chronic post-stroke treatment 63
macrophage polarization to M2 with chronic post-stroke treatment
↑ production of nitric oxide (NO) by means of nitric oxide synthase endothelial (eNOS) in myocardial infarction (MI) 64
stimulation of the adenosine receptor, increasing its synthesis, decreasing reperfusion damage 64, 65
inhibition of TLR4 signaling in MI (indicating ↓ of the production of inflammatory mediators and left ventricular dysfunction) 66
↓ cardiac remodeling, neutrophilic activity and myocardial injury in MI with chronic pretreatment 67