Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

Figure 2

Nutritional ketosis may initiate bioenergetic and mitohormetic signaling through an increase in catecholamines or adiponectin, a decrease in insulin or glycogen, or an increase in β-oxidation that leads to an increase in mitochondrial reactive oxygen species (mtROS) or NAD⁺. This leads to further signaling involving AMP-activated protein kinase (AMPK), silent mating type information regulation 2 homologue 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), forkhead box O 3a (FOXO3a), and nuclear factor erythroid-derived 2-like 2 (NFE2L2), ultimately leading to transcription of genes related to oxidative capacity, mitochondrial uncoupling, and antioxidant defense. These adaptations collectively contribute to resistance against oxidative stress. Other proteins involved include liver kinase B1 (LKB1), which activates AMPK; nicotinamide phosphoribosyltransferase (NAMPT), which facilitates SIRT1 activation through NAD⁺ synthesis; and nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2) and mitochondrial transcription factor A (TFAM), which promote mitochondrial biogenesis.