Program Overview
Not all fat cells are created equal
A growing body of research demonstrates that the nature of adipose tissue, or fat cells, is a significant determinant of obesity. Variations in this tissue—how active or “hungry” it is—affect how much it grows or shrinks in response to dietary intake, and thus whether or not an individual maintains a normal weight or becomes obese.
Unlike traditional perceptions of obesity that view fat accumulation as the passive result of other factors, we view adipose tissue as playing an active role in the disease. This represents a fundamentally new paradigm in how we think about, and potentially treat, obesity. It shifts the focus away from an individual’s “lack of motivation” or “failure of will” and toward the recognition of obesity as a biologically based disease that can be treated with new, specialized drugs.
In order to shrink in size, fat tissue must be stimulated to convert stored triglyceride molecules into free fatty acid molecules that can leave the fat tissue and be burned by energy-requiring tissues of the body. Obese people show reduced rates of fatty acid release from their adipose tissue and a reduced ability to produce ketone bodies, which are a fat-derived fuel source used by muscle and other key tissues. We believe the abnormal fat tissue in obese people can be treated by restoring sensitivity to natural hormonal control mechanisms that reactivate triglyceride breakdown and stimulate ketone body production.
Zafgen has been able to demonstrate the effectiveness of this approach with a number of our lead molecules. Obese animals on our drug quickly and safely return to a normal, lean weight and then maintain that weight in spite of having ongoing free access to food that is high in fat content. Animals treated with our drug that have lost body weight actually consume similar amounts of food as obese mice, yet still maintain a lean, healthy body weight.
This type of treatment, which attacks obesity at its biological foundation, rather than indirectly through artificial appetite suppression, can result in long-term, sustainable weight loss that could make a significant contribution to the improved health and wellness of millions of people.
