Leptin

Butter

I attended a lecture in 2008 about leptin signaling given at Harborview Medical Center through their research programs on diabetes, metabolism and obesity.  The lecture, although highly technical, was  interesting and it gave me plenty to think and read about.

Leptin is what is called a signal transducer.  A signal transducer is an extracellular  signaling molecule that activates a receptor inside or on the cell surface, initiating a series of events, biochemical reactions.    Leptin signaling is involved in a number of areas relating to the management of energy throughout the body, regulating or giving permission for the use of energy for a variety of vital functions.  As I read more about leptin, it led me into a labyrinth of other, associated issues.

Leptin is involved in signaling relating to mesolimbic (dopaminergic) reward centers, food, satisfaction, glycemic control, saiety and reproduction.  Leptin deals with long term energy storage, provision of energy to the brain and gives permission for the use of energy falling within its defined duties.  Intuitively, one wonders what happens if energy demands are requested for things that aren't associated with its associated duties.

Leptin acts to communicate to the Central Nervous System the availability of energy stores.  It acts to restrain food intake and induce energy expenditure, when necessary.   Leptin acts with other systems, such as the Sympathetic Nervous System,  and with factors such as thyroid hormone  and insulin,  in regulating energy use throughout the body and in insuring the thermodynamic  efficiency of skeletal muscle, for example.  Leptin is also involved involved in the cardiovascular system, for example in cardiac hypertrophy.

Leptin is increased, or up-regulated, in obese people.  It increases appetite, generates a low metabolic rate, decreases thyroid function and is impacted by sleep apnea  issues.  Dysregulation of leptin adversely impacts fertility.  Leptin acts on lipid and glucose metabolism.  Leptin also regulates bone metabolism.  This may serve to improve structure with increasing weight by regulating the allocation of higher density bone development.    Leptin resistance occurs during obesity when increasing leptin levels do not have an impact.

Leptin acts in the brain in a neuroprotective  fashion that may also impact memory.  Leptin may be necessary to protect the cell against cell death (apoptosis).

Leptin plays a key role in thermoregulation, working through diverse systems such as the brain's preoptic area and hypothalamus.  Studies in the brown adipose tissue (BAT)  of mice injected by virus indicated involvement of leptin in regulating BAT circuits.  Severely obese mice that lack leptin or its receptor show decreased BAT thermogenesis, and are thus challenged to maintain their body temperature and adapt to cold temperatures.

Leptin may be a key component in considering survival issues under a variety of scenarios or projections associated with climate change modeling.  It may react to a variety of seasonal (zeitgeber) cues, as well as sexual cues regarding melatonin , odor and reproduction.  It will react to hedonistic feelings regarding food, appetite and to the allocation of resources regarding shorter term versus longer term energy needs.

Leptin plays its role along with a host of other players in this complicated web of life.