The statistics on obesity are terrifying.
The condition has tripled since 1975; there are more than 650 million obese people globally, 41 million of whom are children under five.
If nothing is done, the number of obese people worldwide is predicted to rise to one billion by 2030.
In Australia, more than one in four adults are obese, and current non-surgical therapies have side effects or only work in conjunction with exercise, which can be difficult for people who are severely obese. Now, finally, there may have a solution: a nasal spray that works to suppress appetite and increase metabolic rate without exercise in people who are obese.
Australian scientists have unlocked the mystery as to how two naturally occurring hormones impact obesity. The research, published in Cell Reports, reveals the enzymes that control these hormones in the brain.
The researchers, led by Professor Tony Tiganis, from the Monash Biomedicine Discovery Institute, have shown in pre-clinical models that blocking the action of these enzymes (using nasally administered drugs that are already commercially available), leads to a reduction in appetite, an increase in metabolic rate and associated weight loss.
The same research team uncovered the role of two hormones in the control of weight, leptin and insulin, in a landmark paper in 2015. They found that the two hormones – leptin, an appetite suppressant generated in fat cells, and insulin, produced in the pancreas in response to rising levels of glucose in the blood – act in concert on a group of neurons in the brain to stimulate the burning of body fat via the nervous system.
According to Professor Tiganis, obesity occurs when there is an energy imbalance.
“When food intake exceeds energy expenditure, the body gains weight. So to promote weight loss in severely obese people, they need to both lower their food intake and increase energy expenditure – without the need for increased physical exercise, which can often be difficult to maintain,” Professor Tiganis said.
The key to increasing energy expenditure without exercise is to promote the activity of what are called brown and beige adipocytes, or fat cells, in a process called non-shivering thermogenesis.
Insulin and leptin act on a part of the hypothalamus in the brain to increase this brown and beige fat activity, and to decrease appetite.
In this study, Professor Tiganis’ team reveal that elevated levels of two enzymes, called PTP1B and TCPTP, dampen the effects of leptin and insulin, leading to the development and maintenance of obesity in mice.
When the researchers blocked the activity of these two enzymes, this increased insulin and leptin activity, which reduced appetite and increased activity of brown and beige fat cells.
Essentially, blocking these two enzymes led to significant weight loss and improved metabolism despite a high fat diet.
The researchers used a daily dose of a combination of drugs, administered as a nasal spray. These drugs are known to inhibit these enzymes, leading to weight loss and the maintenance of this weight loss.
One of the drugs used, RU486, is used as a contraceptive pill, and is also in clinical trials for the treatment of the metabolic disorder Cushing’s syndrome. The other drug has been trialled for the treatment of type 2 diabetes.
“Both drugs are already commercially available. The data from our studies – and the ease with which they can be delivered in a nasal spray – make them a viable pharmacological approach to promote weight loss in obesity,” Professor Tiganis said.
Obesity is a major driver of worldwide morbidity and mortality, and a major driver of chronic diseases such as type 2 diabetes, cardiovascular disease, liver disease and cancer.
Read the full paper in Cell Reports.
PUBLISHED 12 SEP 2019