Genetic research with mice indicates that weight loss through manipulation of leptin levels may be the foundation of future therapy to treat left ventricular hypertrophy, according to an article in the August 12th issue of Circulation. By altering the signaling pathway of the natural hormone leptin, American researchers were able to reverse left ventricular hypertrophy in obese mice with a genetically abnormal leptin pathway through leptin-induced weight loss.

Although researchers primarily work with leptin in the context of body weight and metabolism, it is known that leptin levels also can affect the heart and blood vessels. American researchers, with Lili A. Barouch, MD, as lead author, chose mice genetically vulnerable to obesity and left ventricular hypertrophy.

In the initial research, investigators compared the hearts of 3 groups of mice at 2, 4, and 6 months old: One group did not have the gene for leptin, a second group did not have the receptor for leptin, and the third was normal. Progressive obesity developed in the two groups of genetically abnormal mice, with left ventricular hypertrophy and individual myocardial cell hypertrophy observed by 6 months of age. The genetically normal control mice showed no such cardiac changes.

Next, researchers divided the 6-month-old obese mice into 3 groups according to future diet: A total of 2 groups were assigned to lose weight (1 by leptin infusions and 1 by a calorie-restricted diet), while the third group continued to eat a regular diet. After 4 to 6 weeks, mice in both diet groups lost the same amount of weight. However, the mice who received leptin infusions had a complete reversal of left ventricular hypertrophy and a partial shrinkage of enlarged myocardial cells, whereas the mice on caloric restriction had no change in left ventricular hypertrophy and a smaller improvement of enlarged myocardial cells.

Barouch noted that species differences in processing of leptin mean that the findings cannot be directly extrapolated to humans: The next stage of research is to evaluate the leptin resistance seen in obese people. "If we can figure out the signaling pathways of leptin [in humans], we can change or minimize the development of left ventricular hypertrophy," Barouch said. "This has tremendous clinical implications ? Left ventricular hypertrophy is a big problem, particularly among obese patients."