Therapeutic Strategy

Peripheral Treatment of Obesity

Human obesity is a worldwide pandemic due to sedentary lifestyle and excessive consumption of energy-dense foods rich in saturated lipids and carbohydrates. Worldwide obesity has nearly tripled since 1975.

Obesity affects all ages and socioeconomic groups. The prevalence of obesity among U.S. adults was 39.8% in 2015-2016. In 2016, more than 1.9 billion adults, 18 years and older, were overweight. Of these over 650 million were obese. Obesity kills more people than underweight.

Being overweight or obese is a major risk factor for chronic diseases, including type 2 diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular diseases, and several cancers. Obesity is a source of reduced quality of life, significant mortality, or permanent disability. 300,000 deaths per year in the United States are related to obesity and medical costs amount to $190 billion annually. Current symptomatic medical and behavioral treatments of obesity fail to achieve their long-term therapeutic goals. Recent therapeutic approaches targeting centrally acting mechanisms have resulted in serious adverse reactions, leading to the non-approval or withdrawal of several anti-obesity medications. Despite a market size estimated to reach $8.4 billion globally by 2022, the few marketed anti-obesity medications have had poor uptake by physicians and patients due to limited efficacy and uncertain safety.

Therefore, there is a need for a convenient, effective and safe medical treatment of obesity and related cardio-metabolic disorders that should significantly reduce health care costs, improve and save human lives.

Mammalian adipocytes are categorized into white adipocytes (WAT) storing energy in the form of lipids and brown adipocytes (BAT) rich in mitochondria and expending energy via uncoupled fatty oxidation. Relatively limited amounts of BAT are required to make significant impact on the energy balance, since as little as 50g of BAT would account for 20% of daily energy expenditure. It is now well established that subcutaneous WAT can evolve into calorie-burning “beige” or “brite” adipocytes. Thus, inducing “browning” of subcutaneous WAT to increase energy expenditures is a promising strategy for treating human obesity and related cardiometabolic disorders. A 15% increase of energy expenditure is believed to be sufficient to safely achieve a significant weight and fat mass reduction while providing meaningful improvement of metabolic parameters.