Why do people who lose weight also experience an improvement in their blood pressure?
Although the effect is well known, surprisingly scientists are unsure as to why weight loss leads to a reduction in blood pressure, and conversely why overweight individuals have higher incidence of hypertension.
A study published in the New England Journal of Medicine has provided evidence that the “melanocortinergic signaling system” is responsible for this phenomenon. Specifically, researchers gave obese volunteers melanocortin agonists, which stimulate melancortin receptors in the human body, to see if this would raise their blood pressure. The use of a MC4R agonist, which stimulates the melanocortinergic system was found to have acutely elevated blood pressure over several days.
The researchers also studied people with a genetic mutation which made them deficient for the Melancortin-4 receptor (MC4R), which predisposes them to obesity. Interestingly, the MC4R group, though obese, appeared to be relatively protected from the effects of their obesity on their blood pressure, apparently due to decreased functioning of their melanocortinergic signalling system.
The authors concluded that the melanocortinergic system significantly affects human blood pressure, and that if MC4R agonists are used in the treatment of certain obese patients that this may actually raise their blood pressure. It is possible that the increase in blood pressure seen in overweight individuals and those who are obese is due to changes in the melanocortinergic system.
How does the MC4R receptor normally function in the human body?
The MC4R, or Melanocortin receptor 4, is activated by alpha melanocyte stimulating hormone and has been implicated in animals models in being involved in the regulation of metabolism, feeding behavior, sexual behavior, and male erectile function. MC4R mutations are the most common genetic defect predisposing people to obesity and are present in 1 to 2.5% of obese people. MC4R may also be activated by a large molecule called Pro-opiomelanocortin (POMC), which is the source of several hormones, including ACTH, beta-LPH, beta-MSH, and gama-MSH and others.
While therapeutic treatments which modulate the melanocortinergic system to improve blood pressure in obese individuals are not yet available, weight loss can significantly lower blood pressure in those who are overweight or obese.
Modulation of Blood Pressure by Central
Greenfield, J. R. M.D., et al.
N Engl J Med 2009; 360:44-52January 1, 2009