Leptin undercover activities

Leptin and cardiovascular disease (Photo: Gabriela Camerotti)

Leptin and cardiovascular disease (Photo: Gabriela Camerotti)

In a previous post we discussed the beneficial effects of leptin, the satiety hormone, in normal weight individuals. Leptin, produced by fat cells, tells the brain when we should stop eating. Makes sense.

More problematic is the situation in obese individuals where the leptin feed-back on food intake has stopped working.

If that wasn’t enough, it gets even worse. While high levels of leptin don’t help obese individuals lose weight, new research even show that they can directly contribute to cardiovascular disease.

A double whammy

It seems ironic that fat makes leptin, but obese individuals with excessive fat accumulation become insensitive to leptin’s impact on their metabolic, but not their cardiovascular system. Exactly why leptin cannot tell our brain to stop eating, but it can still tell the body to increase the activity of the cardiovascular system is a conundrum.

At least new research findings have explained the second part of the equation. In both cell culture and animal models, the researchers have shown that leptin directly activates aldosterone synthase expression in the adrenal glands, resulting in production of more of the steroid hormone aldosterone. That is not good.

High aldosterone levels are known to contribute to widespread inflammation, blood vessel stiffness and scarring, enlargement and stiffness of the heart and impaired insulin sensitivity. It also has a direct effect on blood pressure by regulating salt-water balance in the body. But exactly how it got high in obesity was a mystery.

Possible treatment on the way

Results so far from mice (Photo: Wikimedia)

Results so far from mice (Photo: Wikimedia)

Identifying the direct connection of high levels of leptin and aldosterone is a break-through in understanding the cause of the increased cardiovascular disease  risk in obese individuals. So far only in mice, but early results from human trials show the same correlation, and strongest in females, who make much more leptin.

There are already existing drugs that could work to ameliorate the situation, including an old blood pressure drug, spironolactone, that directly targets aldosterone activity. Spironolactone, a diuretic, helps the kidney eliminate water and sodium but hold onto valuable potassium. It works by blocking the receptor to which aldosterone binds.

There are also leptin receptor blockers under study for a wide range of problems from obesity to cancer.

So better know your leptin undercover activities to keep healthy.

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