"Organisms need to be able to temporarily adapt to the stress of hypoxic conditions until the situation changes, so when inflammatory cells see this kind of signal, they come to the hypoxic area to do their normal job, which is to basically eat damaged cells," Kim said.
In obesity, however, fat cells are in a chronic state of hypoxia.
"If you look at adipose, or fat tissue, in the obese, there is massive and chronic inflammation," he said. "It's a defense mechanism. The inflammatory cells are really good guys, but as obesity persists, inflammation becomes chronic.
"HIF-1 alpha is important for hypoxia adaptation, but it's constantly activated in the obese, and that's where it turns bad," Kim said. "In the obese, HIF-1 is aberrantly and chronically elevated and is the master regulator of ominous chronic inflammation."
To study the effect HIF-1 alpha might have on the development of insulin resistance and diabetes, Kim and his colleagues used genetic engineering techniques to completely remove, or "knock out" HIF-1 alpha from adipose tissue in obese mice.
"Once we knocked out HIF-1, everything got better," he said. "The fat cells survived and the mice remained obese, but we saw less inflammation in the fat tissue. These mice responded better to insulin than their normal counterparts, which means insulin sensitivity was improved and glucose tolerance was improved."
Kim said several pharmaceutical companies are developing HIF-1 alpha inhibitors to block the protein from functioning, which might one day result in medications to treat type 2 diabetes and insulin resistance in obese people. But the primary reason the pharmaceutical industry is already investigating HIF-1 alp
|Contact: Amanda Siegfried|
University of Texas at Dallas