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Leptin gene therapy

Leptin gene therapy can aid weight loss

Injecting a gene into the brain that codes for the hormone leptin may curb overeating, leading to long-term weight loss.
The team found the mice that received the leptin gene therapy did not lose bone mass

Researchers from Oregon State University have claimed that there may be a more effective alternative to dieting to achieve weight loss, brain injections of the appetite-suppressing gene. In a study. ‘Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss’, published in the Journal of Endocrinology, researchers describe how injecting a gene into the brain that codes for the hormone leptin may curb overeating, leading to long-term weight loss.

Leptin is a hormone secreted by adipose cells that plays a role in regulating energy balance by curbing hunger. Often referred to as the satiety hormone, leptin works by sending signals to the brain that tell us when to stop eating. The amount of leptin released by fat cells is dependent on the amount of body fat a person has; the greater the amount of body fat, the more leptin that circulates in the blood. People who are obese have very high leptin levels, but their brain often stops responding to the hormone as a result, causing them to overeat.

While dieting and exercise are often the first port of call for people who want to lose weight, study author Dr Urszula Iwaniec, of Oregon State University, and colleagues note that such strategies often fail to have prolonged success.

Urszula Iwaniec

"In this study we show that leptin gene therapy causes effective long-term weight loss while maintaining bone mass,” said Iwaniec. “Novel approaches like leptin gene therapy for treating obesity are needed to address this public health crisis."

"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," they note.

They add that repetitive weight loss and weight gain can take its toll on bone health, raising the risk for osteoporosis - a disease in which the bones become weak, increasing fracture risk.

"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," say the authors.

For their study, the team set out to determine whether leptin gene therapy could be one such strategy.

The researchers injected the brains of seven adult female rats with a recombinant adeno-associated virus that encoded the gene for rat leptin, called rAAV-Leptin. The results were compared with two control groups of rats; one group was injected with a recombinant adeno-associated virus called rAAV-GFP, while the other group received no injection.

All rats were weighed at the beginning of the study and 18 weeks after, and their food intake was monitored weekly. The researchers also assessed the rats' bone mass at study end.

While the mice that received rAAV-GFP gained weight, those that received the leptin gene therapy consumed less food, lost weight and were able to maintain their lower body weight over the 18-week study period. In addition, the team found the mice that received the leptin gene therapy did not lose bone mass.

Overall, they found that rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). The rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

Though further research is warranted to determine whether leptin gene therapy would be safe and effective for humans, the team believes their findings suggest it may be a promising strategy against obesity - one that does not have negative implications for bone health.

“This is an interesting study which adds to our knowledge about the actions of the hormone leptin on the brain and, in particular, that it can influence fat stores and bone density,” said Professor Stephen O’Rahilly, President of the Society for Endocrinology and Professor of Clinical Biochemistry and Medicine, University of Cambridge. However it is purely a study in an animal model and not of immediate or direct relevance to the treatment of human obesity or osteoporosis.”

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