A hormone predominantly found in our guts may help us absorb fat from our diets and could contribute to the development of obesity under certain circumstances, according to a newstudy published Wednesday in Nature.
The researchers, primarily hailing from the University of Kentucky, conducted a series of experiments on lab mice, fruit flies, and humans that examined how the hormone, called neurotensin (NT), functions in the gut. Mice deficient in NT proved less able to absorb fat from food and they appeared to be protected from conditions like obesity, fatty liver, and insulin resistance that are associated with a high-fat diet. On the other hand, fruit flies engineered to produce NT accumulated more fat in their bodies than normal.
Aside from seeing a similar fat absorption effect in human gut cells, the researchers also analyzed data from an earlier, long-running population study of middle-aged adults and found that obese and insulin-resistant individuals were more likely to have high levels of a precursor hormone, Pro-NT, in their blood. Those who weren’t obese but had the highest levels of Pro-NT were more than twice as likely to eventually develop obesity than people with the lowest levels of Pro-NT.
“Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment,” wrote the authors.
An Unintended Consequence
According to senior study author Dr. B. Mark Evers, the director of the Markey Cancer Center, NT’s role in obesity is an unintended consequence of evolution.
“From an evolutionary standpoint, hormones like NT are very valuable since early humans may only be able to eat sporadically depending upon their ability to obtain food and availability of food. Therefore, you would want a hormone like NT that helps to absorb all available fat that can be stored until the next meal,” Evers told Medical Daily in an email. “Unfortunately, with the abundance of the ‘Western’ diets which contain more fat, the body doesn’t know the difference and continues to try and absorb the extra fat.“
The hormone is also found in our central nervous system, where it plays a more localized role in regulating how we move and experience stress and pain, Evers explained. And there’sevidence showing that NT may be involved in the development of brain-related conditions like depression, drug abuse, and Parkinson’s Disease.
Evers’ laboratory has studied NT for nearly 25 years, primarily focusing on how exactly our intestinal cells secrete the hormone, how the gene responsible for it is regulated, and its potentially damaging effects on the human body elsewhere. Their work has shown that many tumors contain receptors for NT and use it to grow. Motivated by this earlier research as well as a 2012 study in the Journal of the American Medical Association that found an association between pro-NT blood levels and breast cancer as well as cardiovascular disease and diabetes — both obesity-related conditions — his team theorized there might be a more direct connection between obesity and NT. In fact, all four conditions may be connected, since obesity leads to chronic inflammation, a risk factor for cancer.
“With our current findings showing a relationship of NT with obesity, it is interesting to speculate that increased NT levels shown with obesity could also contribute to an increased incidence of certain cancers,” said Evers.
Though that theory will require more science to validate, there could be immediate applications from this field of research. Evers noted that there are already companies like German-based Sphingotec who have developed Pro-NT tests to help patients predict their breast cancer risk. It could soon be possible to use NT as a biomarker for obesity, Evers said.
A Robust Study
“The methodology of the study is very robust,” Dr. W. Conan Mustain, a surgical oncologist at the University of Arkansas for Medical Sciences, told Medical Daily. “Obviously, anything in a mouse model requires some degree of interpretation before you apply it directly to humans, but I certainly think the science behind their findings is justified.” Mustain previously worked at the Markey Cancer Center as a research fellow but is unaffiliated with the current study.
He noted that the NT-deficient mice were on average slightly thinner than normal, a finding that adds mystery to another popular theory concerning NT and its connection to the hormone leptin. Leptin is known to turn off feelings of hunger, and some suspect that NT allows the hypothalamus to properly respond to its presence in our body. Without NT receptors, Mustain explained, the mice should have been immune to leptin and thus unable to easily control their hunger. That they became even thinner suggests that link is more complicated than it might appear and warrants further exploration.
Likewise, obesity is a complex condition with varying risk factors and causes depending on the person. And the study only looked at NT’s role in obesity triggered by a high-fat diet. “Other causes of obesity could include an overabundance of carbohydrates and it is doubtful that NT plays a role in this aspect,” said Evers.
Regardless, the future of research on NT and obesity appears plenty bright.
“Anytime we find a link like this, it’s exciting, and it should be investigated,” said Mustain. “I think there’s great potential for it. But we need to understand more.”
Source: Li J, Song J, Zaytseva N, et al. An Obligatory Role for Neurotensin in High-Fat-Diet Induced Obesity. Nature. 2016, Medical Daily
