We need to consume fat to survive, but a new study has shown that the human body can process different types of fats in different ways. Over the years, studies have indicated that some types of fat are healthier than others. For example, saturated fat can increase inflammation and the risk of metabolic disorders. In the Western world, the typical diet tends to be high in sugars and fats, saturated fats in particular. There are healthier fats, which are monounsaturated and polyunsaturated, that can help protect the heart and liver from damage. But these healthier types of fats are less common in Western diets compared to unhealthy saturated fat. Scientists sought to learn more about how these various types of fats are used and metabolized, and hope they can affect the body.
In a new study, researchers study showed that molecules known as bile acids, which are crucial to breaking down fat in the intestine, can also affect how fats are absorbed. The findings have been reported in Cell Metabolism.
"We found that if you can tweak bile acids, you can find a way to selectively absorb the good fats and excrete the bad fats, with many metabolic benefits," said Thomas A. Vallim, PhD, a researcher and professor of medicine in the UCLA Division of Cardiology.
Bile acids break fats down so they can be absorbed and move through the body. This was a helpful characteristic in ancient times when food was more scarce, but has become a disadvantage for people who are now spoiled for choice in their diet.
In this study, the researchers used a mouse model and CRISPR gene-editing tools to remove an enzyme called CYP7A1 that is essential for the production of bile acids; they wanted to know if fat absorption was reduced. Another group of mice was given a drug known as orlistat to block fat absorption. Both groups were fed a Western-style diet. Both groups of mice absorbed less fat than untreated mice, but only the mice lacking CYP7A1 also did not gain weight.
Mice that got orlistat also ate more. Additional work showed that mice lacking CYP7A1 were also releasing more glucagon-like peptide-1 (GLP-1) hormones, which can stop weight gain by reducing appetite. The fat was being absorbed lower in their intestines, triggering the release of GLP-1.
"We think what's happening is that as these fats travel further into the gut, they stimulate some receptors that promote the secretion of GLP-1," added Vallim. "That's a way that your body tells your brain, 'Hey, I've had enough of this nutrient.'"
Mice that got orlistat were just reducing the absorption of fats. But in mice that weren’t producing CYP7A1, the livers began to carry higher levels of polyunsaturated fats that are healthy, and less saturated, unhealthy fat.
When they tracked the absorption of fatty acids, the researchers showed that in mice lacking CYP7A1, polyunsaturated, good fats were absorbed, but saturated, bad fats were being released into feces.
Higher levels of bile acids were needed to break down saturated fats compared to unsaturated fats, so the saturated fats were not easily or quickly absorbed.
Not all bile acids move fat the same way, either. The elimination of one particular bile acid known as cholic acid could drastically reduce saturated fat absorption, but unsaturated fat absorption was unaffected.
"We think there is a lot of potential in targeting this system and maybe specific bile acids," Vallim said. "We're interested in pursuing all those avenues and, potentially, in developing new therapies."
Sources: UCLA, Cell Metabolism