Leptin is a neurotransmitter that is produced in fat cells and is involved in appetite. Leptin works through the action of several small proteins called neuropeptides, such as thyrotopin-releasing hormon. Many of these neuropeptides are first made in a longer inactive form (called a prohormone) and are subsequently cut into a smaller active form; this is called prohormone processing. While leptin is known to regulate energy balance by controlling whether these neuropeptides are produced in any form, Eduardo Nillni and colleagues, from Brown Medical School and Rhode Island Hospital, theorized that leptin might have an additional layer of control, by regulating the production of the enzymes that are used to convert the inactive prohormones to the smaller active hormones. They tested their hypothesis by examining leptin’s effect on two enzymes prohormone convertase 1 and 2, these enzymes cut the prohormone form of thyrotopin-releasing hormone into its active form. In cell culture of neuronal cells from the hippocampus (the area of the brain where leptin acts), leptin treatment led to a significant increase in the expression of these two enzymes at both the genetic and protein level.
Rats that were starved, and thus had low levels of leptin in their blood serum levels also had lower levels of these two enzymes. Consistent with the lower levels of the enzymes, these fasted rats likewise did not have a significant amount of the active (cleaved form) of thyrotopin-releasing hormone. Giving leptin directly to these rats, increased enzyme levels and, inevitablely, the amount of active thyrotopin-releasing hormone. These data provide evidence for an additional key regulatory point in the control of energy balance through leptin and may suggest novel therapeutic strategies for treatment of obesity and thyroid axis–related diseases.
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Author contact:
Eduardo A. Nillni Brown Medical School/Rhode Island Hospital, 55 Claverick St. Providence, RI 02903, USA.
Phone: 401-444-5733; Fax: 401-444-6964; E-mail: Eduardo_Nillni@Brown.edu
Journal
Journal of Clinical Investigation
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