The role of AMPK, both in energy regulation and fat loss, should be highlighted more often. In particular, AMPK activation (either due to insulin sensitizers, insulin-independent glucose-disposal agents
, PPAR-gamma activators, adipokines such as leptin and adiponectin, stress, or exercise), has short term and long(er) term effects. Short-term, AMPK activation stimulates cells to switch from active ATP consumption (synthesis of fatty acids and glycerol) to active ATP production
(oxidation of fatty acids and glucose). Longer-term, AMPK activation impacts protein and insulin syntheses, gene expression, and appetite regulation. These longer-term effects not only have significance for metabolic processes in muscle cells and adipose tissue, but also in liver, heart, and pancreatic cells. The fat loss effects can be traced to the impact of AMPK activation on insulin metabolism and oxidation of fatty acids. In particular, by stimulating the translocation the GLUT-1 and GLUT-4 proteins, AMPK activation enhances glucose uptake, leading to enhanced glycolysis and elevated ATP production.
Furthermore, by inhibiting the action of the enzyme, hormone sensitive lipase (HSL), AMPK activation ensures that the HSL-induced rate of release of fatty acids from triglycerides (that would normally induce higher ATP levels due to oxidized fatty acids) does not exceed the rate of fatty acid oxidation
. This serves to hinder fat accumulation. Along these lines, the impact of AMPK activation on peroxisome proliferator-activated receptor gamma (PPAR-gamma), a receptor with primarily adipocyte domicile and activity, leads to increased insulin sensitivity and fatty-acid oxidation in hepatic and skeletal muscle cells. This occurs mainly via the action of the adipokine, adiponectin, that triggers glucose uptake and fatty acid oxidation in skeletal muscle cells, while promoting fatty acid oxidation and inhibiting gluconeogenesis in hepatic cells. In summary, AMPK activation can produce beneficial effects on fat loss via some of the mechanisms addressed earlier.