1.
Molecular Basis of the Beneficial Actions of Resveratrol.
Repossi, G, Das, UN, Eynard, AR
Archives of medical research. 2020;(2):105-114
Abstract
Resveratrol modulates the transcription factor NF-κB, cytochrome P450 isoenzyme CYP1A1, expression and activity of cyclooxygenase (COX) enzymes, Fas/Fas ligand mediated apoptosis, p53, mTOR and cyclins and various phospho-diesterases resulting in an increase in cytosolic cAMP levels. Cyclic AMP, in turn, activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway that facilitates increased oxidation of fatty acids, mitochondrial respiration and their biogenesis and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17) and other pro-inflammatory molecules and inhibits expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) that may explain its anti-inflammatory actions. Polyunsaturated fatty acids (PUFAs) and their anti-inflammatory metabolites lipoxin A4, resolvins, protectins and maresins have a significant role in obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome and cancer. We observed that PUFAs (especially arachidonic acid, AA) and BDNF (brain-derived neurotrophic factor) protect against the cytotoxic actions of alloxan, streptozotocin, benzo(a)pyrene (BP) and doxorubicin. Thus, there is an overlap in the beneficial actions of resveratrol, PUFAs and BDNF suggesting that these molecules may interact and augment synthesis and action of each other. This is supported by the observation that resveratrol and PUFAs modulate gut microbiota and influence stem cell proliferation and differentiation. Since resveratrol is not easily absorbed from the gut it is likely that it may act on endocannabinoid and light, odor, and taste receptors located in the gut, which, in turn, convey their messages to the various organs via vagus nerve.
2.
Developmental origins of adult health and disease: The metabolic role of BDNF from early life to adulthood.
Briana, DD, Malamitsi-Puchner, A
Metabolism: clinical and experimental. 2018;:45-51
Abstract
Accumulating evidence suggests that the origins of adult disease may occur during fetal life. Thus, the concept of "developmental programming" has been introduced and supported by epidemiological and experimental data. This concept supports the idea that the nutritional and hormonal status during pregnancy could interfere in metabolism control. The mechanisms responsible for this "developmental programming" remain poorly documented. Current research indicates that neurotrophins and particularly brain-derived neurotrophic factor (BDNF) may play a crucial role in this process. Although mainly expressed in the nervous system, BDNF and its receptor, tropomyosin-related kinase B (TrkB), are immunolocalized in several regions of the human placenta and have important functions during pregnancy. BDNF serves widespread roles in regulating energy homeostasis in both fetuses and adults, by controlling patterns of fetal growth, adult feeding and physical activity, and by regulating glucose metabolism in peripheral tissues. Impaired BDNF signaling may be implicated in the etiopathogenesis of the metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes and neurological disorders. The aim of this article is to provide a brief comprehensive literary review regarding the potential implications of BDNF in "developmental programming", through regulation of metabolism and energy balance from early life to adulthood.