The CDC reports that a staggering 61% of adults in America are clinically obese, and therefore at increased risk of developing other serious illnesses such as diabetes, stroke, heart disease and even cancer. While diet and activity level certainly contribute, it has become increasingly clear that biology plays a role in the tendency to become obese.
There is hope that by studying the genes and proteins that regulate fat cells, scientists will uncover information that will form the basis for development of new treatments for obesity.
A new study published in the March issue of Developmental Cell identifies a cellular mechanism that regulates the formation of fat cells.
The authors of the study, led by Dr. Amato Giaccia of Stanford University, examined the effect of low oxygen, or hypoxia, on the generation of mouse fat cells.
The rationale for these experiments comes from previous physiological evidence, including the observation that training at high altitude, where oxygen levels are lower, enhances body fat reduction.
The scientists used mouse cells that can be stimulated to become fat cells following treatment with specific hormones. They compared cells maintained in normal oxygen with those maintained in hypoxic conditions and found that low oxygen levels inhibited fat cell development.
They then went on to show that a protein called HIF-1 (hypoxia-inducible factor-1) is present in the cells that failed to develop into fat cells. Cells specially engineered to be missing HIF-1 were able to develop into fat cells even in hypoxic conditions, showing that HIF-1 plays an important role in the regulatory mechanism.
Giaccia and colleagues also found that PPARg, a gene known to be crucial for fat cell development, was inhibited in hypoxic conditions. They believe that DEC/Stra13, a gene regulated by HIF-1, may be directly responsible for inhibiting specific genes such as PPARg that stimulate fat cell production.
The scientists are careful to point out that fat cell development is very complex and the inhibitory mechanism includes elements in addition to the genes and proteins examined in this study. However, they are optimistic that their results will provide potentially useful targets for future treatments.
“Our study provides a different perspective on fat cell development in a simplified system. Nevertheless, our findings suggest a new approach for regulating fat cell generation which may potentially be beneficial to the development of therapies for obesity and/or diabetes," said Giaccia.
[Contact: Amato J. Giaccia]
04-Mar-2002
