The link between obesity and cardiovascular diseases is well acknowledged. Being obese or overweight is a major risk factor for the development of elevated blood pressure, and cardiovascular diseases. But it has net been known how obesity increases the risk of high blood pressure, making it difficult to develop evidence based therapies for obesity, hypertension and heart disease.
In a ground-breaking study, published today in the prestigious journal, Cell (embargo midday EST), researchers from Monash University in Australia, Warwick, Cambridge in the UK and several American universities have discovered the link between obesity and hypertension. This research has discovered that the hormone leptin which is secreted by fat cells is significantly elevated following weight gain and in obesity, acts in the brain to elevate blood pressure. These studies, involve both animal and human experiments, including a unique cohort of patients lacking the hormone leptin or lacking the leptin receptor. Results demonstrated that both blocking leptin from producing its actions in the brain and removal of the leptin receptors, from the brain were effective at for the reducing obesity induced hypertension. As much as 80% of common hypertension is caused by excess body fat, and this study for the first time describes the mechanism by which obesity elevates blood pressure, and opens up new approaches to treat obesity induced high blood pressure.
The study - led by Professor Michael Cowley, Director of the Monash Obesity & Diabetes Institute within the School of Biomedical Sciences, Monash University, Australia - used a number of new and unique technologies to link leptin in obesity induced hypertension:
- In genetically engineered mice, only those with normal leptin signalling showed an increase in blood pressure when they became obese
- This rodent data was confirmed in human studies, in which obese leptin-deficient and leptin receptor deficient patients had lower systolic blood pressure compared to aged and BMI matched controls
- Restoring leptin receptors to the brain of obese leptin receptor deficient mice increased their blood pressure
- Multiple blockage methods of the leptin receptor in the brain, reduced the hypertension of obese mice
- Acute blockage of the electrical activity of the leptin receptor expressing cells in the brain of obese hypertensive mice, immediately reduced their blood pressure, confirming the role of these neurons in elevating blood pressure in obesity,
"This study shows that a hormone secreted by fat (leptin) increases blood pressure, and explains the mechanism of the known link between obesity and high blood pressure."
"Our data suggest that pharmacological approaches based on altering the effect of leptin in the dorsomedial hypothalamic region of the brain, could potentially represent a therapeutic target for the treatment of obesity induced hypertension and potentially could be exploited to alleviate the incidence of obesity induced cardiovascular diseases."
The researchers are now investigating whether blocking the leptin receptor may be a way to reduce the incidence of hypertension and cardiovascular diseases in obesity. The anti-hypertensive drug market is expected to exceed $40 billion annually by 2018.
*World Preview 2018 report by Evaluate Pharma.