Leptin Gene Therapy Shows Promise For Weight Loss

Though dieting and exercise are often touted as the safest and most effective way to lose excess weight, many people still find that the results don’t always stand the test of time. New research suggests that brain injections of the gene that encodes leptin – known as the ‘satiety hormone’ – could be more effective at helping individuals lose weight.

Dr. Urszula Iwaniec, of Oregon State University, and colleagues are researching the strategy, which could help people feel fuller, faster preventing overeating and resulting weight gain. Leptin acts to trigger feelings of satiety by sending signals to the brain.

Leptin is released from fat cells – or adipose tissue – once an energy input level has been met, increasing feelings of fullness. The amount of leptin released is directly proportional to the amount of body fat a person has; the higher the percentage of body fat – and therefore the higher the number of hormone-releasing fat cells – the more leptin is excreted into the blood stream.

The balance of energy in an obese individual is somewhat paradoxical; since they have a large amount of body fat, they produce very high levels of leptin but like insulin insensitivity in diabetic patients, the brains of obese individuals often begin to ignore the leptin-induced signal, leading to overeating.

“Unfortunately, the long-term efficacy of conventional weight loss interventions is generally poor and many individuals weight-cycle through repetitive bouts of weight loss followed by rapid weight regain,” said the study authors. The research was published in the Journal of Endocrinology.

The study authors note an additional risk associated with major fluctuations in weight – recurring weight loss and weight gain can raise a person’s risk of osteoporosis and bone fractures, due to the added strain placed on the skeletal system. “Because osteoporotic fractures are associated with decreased quality of life and increased mortality, there is strong incentive to develop weight loss strategies that preserve bone mass.”

To test whether leptin gene therapy could be effective as a weight-loss aid, Iwaniec and her team injected a recombinant adeno-associated virus that encoded the gene for rat leptin – called rAAV-Leptin – into the brains of seven adult female rats. The researchers are designed two control groups of rats; one group of subjects received an injection of the rAAV virus containing the gene for green fluorescent protein (GFP) – called rAAV GFP – while the other group received no injection at all.

The rats from all three groups were weighed before the start of the study, and again after 18 weeks. The bone mass of the rats was also measured at the end of study, and the food intake of the rats was monitored on a weekly basis.

The results were surprising: rats that were administered the leptin gene therapy not only lost weight, but consumed less food overall and were successful in maintaining the weight loss over the 18-week study period. Those same rats also showed no decrease in bone mass.

The rats that received the rAAV-GFP gene therapy gained weight over the course of the study. According to Iwaniec, “In this study we show that leptin gene therapy causes effective long-term weight loss while maintaining bone mass. Novel approaches like leptin gene therapy for treating obesity are needed to address this public health crisis.”

More research will still need to be conducted in order to determine whether leptin gene therapy would be a safe and effective therapy for weight loss in humans, however the study investigators are optimistic that this could be a promising treatment for obesity. Approximately 35% of US citizens are considered to be obese, and face an increased risk of stroke, heart disease, type 2 diabetes, and certain forms of cancer.

Sources:

• Leptin gene therapy ‘may be better than dieting’ for weight loss – http://www.medicalnewstoday.com/articles/301213.php
• Turner, R., Dube, M., Branscum, A., Wong, C., Olson, D., Zhong, X., Kweh, M., Larkin, I., Wronski, T., Rosen, C., Kalra, S., Iwaniec, U. (2015). Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss. J Endocrinol.