This effect was seen in both lean and obese mice in a new study.
New research, which appears in the journal Nutrition & Diabetes, has found that a particular pathway that promotes the feeling of fullness becomes blocked after too many calories are consumed.
Obviously, this breeds a problem because people may continue overeating if an excess of calories blocks the production of the hormone that signals the feeling of being full, called uroguanylin. Previous research has shown that uroguanylin plays a role in obesity and may have implications for weight loss treatments.
In the research, the scientists studied mice — both lean and obese — who were overfed. They observed that the production of uroguanylin was blocked in the small intestines once the animals had consumed too many calories.
Interestingly, the uroguanylin receptors in the brain were still intact, and had even increased in number, but the hormone itself was no longer being produced.
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"What's interesting is that it didn't matter whether the mice were lean and overfed, or obese and overfed -- urogaunylin production stopped in both groups of animals when they got too many calories,” Dr. Scott Waldman, Chair of the Department of Pharmacology and Experimental Therapeutics at the Sidney Kimmel Medical College, said in a press release.
"Here, it's not the obese state that's causing the problem but rather it's the calories," he added.
The researchers investigated how overeating manages to shut down the production of uroguanylin by studying the cells in the small intestine that produce the hormone. They had a hunch that a cellular organelle, called the endoplasmic reticulum (ER), might be involved — and they were spot on.
The ER serves as a production line for a number of proteins and hormones in the body, and when it’s stressed, it can stop functioning. By applying a chemical known to cause ER stress, called tunicamycin, the mice stopped producing uroguanylin just as they had when they were overfed.
Then, the researchers gave the overfed mice a chemical known to relieve ER stress, tauroursodeoxycholic acid (TUDCA), and the animals once again began producing uroguanylin.
Similarly, when the animals were put on a diet, the production of the hormone resumed.
"Like in cancer, there are many steps on the way to becoming obese that aren't easily reversed,” said Dr. Waldman. “While the uroguanylin hormone pathway appears to be one of those steps, we don't yet know whether it's important early on in the process, or later, and how much of a role in plays.”
More research will be required to continue unveiling uroguanylin’s role in both the onset and prevention of obesity.
"But in combination with other approaches, hormone replacement of uroguanylin may become an important component of therapy to reverse obesity,” Dr. Waldman concluded.
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