According to the World Health Organization 39% of all adults worldwide were overweight, and 13% had obesity. These conditions are associated with diabetes, cardiovascular disease, and some cancers. Changing exercise and dietary habits can help people maintain a healthy weight. However, taking these steps effectively can be challenging for many reasons. Over the years, various drugs that suppress the appetite by acting directly on neurotransmitter systems in the brain have been withdrawn from the market due to adverse effects, particularly involving mood and the function of the heart.
“Most current prescribed treatments are aimed at reducing food intake by targeting the central nervous system,” says Dr. Yanchuan Shi, who leads the neuroendocrinology group at the Garvan Institute of Medical Research, in Sydney, Australia. “However, these can have significant psychiatric or cardiovascular side effects,” she notes. Dr Shi and colleagues wanted to test a new way of reducing weight gain without affecting the central nervous system.
Conserving energy stores
The team focused on a nerve signaling molecule called NPY. It helps many animals, including mice and humans, survive conditions in which food shortages are commonplace. NPY increases food intake and conserves energy stores by reducing heat generation in a type of fat tissue called brown adipose tissue. In an environment where people have ready access to food and do not get sufficient exercise, however, NPY may make it particularly difficult to lose weight.
“NPY is a metabolism regulator that plays a critical role during states of low energy supply, where it helps store fat as a survival mechanism,” says Prof. Herbert Herzog, head of the Eating Disorders Lab at the Garvan Institute. Today, however, these advantageous effects can exacerbate existing diet-induced weight gain, leading to obesity and metabolic disease.”
Dr. Shi, Prof. Herzog, and colleagues investigated the effects of a drug called BIBO3304 on mice and human fat cells from people with obesity. The drug blocks a type of cell receptor for NPY called Y1 that is found in fat tissue and other tissues in the body. Crucially, BIBO3304 cannot cross the blood-brain barrier, so it is unlikely to adversely affect mood.
