AMPK

The role of AMPK in peripheral tissues has long been established. However, its role in the hypothalamus has just begun to be explored. Among other things, AMPK is a energy sensor molecule.In peripheral tissues signals a low energy state.It can be described as the body's "fuel gauge". Its role in the hypothalamus is more complex. It is involves in the regulation of appetite.

AMPK is a heterotrimeric protein kinase with one catalytic subunit, and two regulatory subunits. It is activated by an increase of the AMP:ATP ratio, which can be caused by hypoxia, heat shock, exercise, low glucose or other metabolic stresses. Phosphorylation of a threonine (T172) is required for the enzyme to be active. AMPK activates catabolic pathways that generate ATP and inhibits anabolic pathways that use up ATP. Glycolysis is upregulated by AMPK. AMPK activated glycolysis by increasing the amount of fructose-2,6-bisphosphate, increasing glycolysis and decreasing gluconeogenesis. AMPK activates ACC by phosphorylating and is located in the neurons of the hypothalamus with little expression in glia as shown in figure 2a. The exact role of AMPK in neurons is unknown, but as a result of recent studies it is hypothesized that it plays a pivotal role in total energy level perception. In other words, it is implicated in global energy regulation by its involvement in the energy level of neurons in the hypothalamus. Since appetite is regulated by the hypothalamus, and AMPK signals a low energy state, then AMPK increases food intake.

A problem with using AMPK as a target to battle obesity is that it is involved in many cellular processes. Modulating its activity would certainly have many other effects on the organism, along with the decreased effect of decreasing food intake. Figure 2b shows some of the major biological activities that AMPK affects.

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