Leptin: A Familiar Hormone


Figure 5: Taken from the University of Arizona Department of Biochemistry. This is a concise drawing which indicates some of the pathways for leptin that are already known.

Known Pathways of Leptin:

Leptin is released by adipocytes.   It then travels through the blood to the hypothalamus, where it interacts with its receptor. There it relays information about the body's levels of stored fat.  This Hormone is known to be involved in:

  1. Regulation of food intake and hunger - including the oxidation of excess fatty acids

  2. Adipose tissue formation

  3. Regulation of Reproduction and Fertility - this is actually related to leptin's ability to report on the quantity of fat stores in the adipose tissues. If a woman does not have adequate fat, she will become infertile.

As a result of this relay, in times of excess fat, Leptin can  cause fatty acid oxidation to be "uncoupled" from oxidative phosphorylation - that is, that energy obtained from the oxidation of fats is released as heat instead of being used to generate ATP. The fact that Leptin stimulates fatty acid oxidation is already known.  The new pathway for Leptin simply explains how this stimulation occurs.


Figure 6: The structure of Leptin.

The Structure of Leptin:

Leptin is a four chain helical bundle.  It's structure resembles that of other members of the cytokine signaling family, such as  growth factors.

 


Figure 7: The increase of of AMPK activity in soleus muscle after the i.v. injection of leptin. There is a sharp increase after approximately 20-30 minutes, and then another increase after 360 minutes.


Figure 8: Phosphorylated AMPK is observed after 15 minutes in both denervated and intact skeletal muscle but not after 6 hours in denervated muscle.

How does Leptin act in the New Pathway?

In the new pathway, Leptin has been shown to stimulate oxidation of fat in a delayed fashion as well as soon after being injected directly into skeletal muscle.  This indicates that leptin may stimulate the new pathway by either acting directly at the site of injection, or by first traveling to the brain. This is evidenced more completely by the fact that AMPK activity is still stimulated 15 minutes after i.v. leptin when motor nerves are blocked but not stimulated 6 hours after i.v. leptin. AMPK activity is also stimulated after leptin is injected directly into muscle ex vivo.

 

     

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The Department of Biochemistry and Molecular Biophysics
krclark@u.arizona.edu