乌鸦传媒

BOSTON -- Liraglutide (Victoza, Saxenda) may be associated with weight loss because of its effect on glucagon-like peptide 1 (GLP-1) receptors in the brain, which have been discovered for the first time in humans, according to researchers here.

In a two-part study, that liraglutide was associated with a decrease in the attractiveness of fatty foods, as as measured by functional MRI (fMRI) studies, possibly because of GLP-1 receptors in the brain, which had previously only been found in the brains of rodents and nonhuman primates, said , of Harvard Medical School in Boston, and colleagues, at a presentation at the Endocrine Society annual meeting.

In addition, the receptors were seen only in the hypothalamus in other species, but Farr and colleagues said they found evidence of GLP-1 in the medulla oblongata, parietal cortex, and hypothalamus in the 22 participants in the the first part of the study, who underwent immunohistochemistry (IHC) tests.

"Nobody has really looked closely at how liraglutide works in the brain," Farr noted.

"I think this is a great paper," commented , of Tulane University in New Orleans. "It's a very interesting concept, and it needs to be studied more."

Fonseca, who chaired the session where the study was presented, added that a greater understanding of liraglutide's mechanism in the brain may yield greater clinical application.

Injectable liraglutide is an analog of the GLP hormone that controls metabolism and appetite. Used at 1.8-mg doses, liraglutide can lead to weight loss in people with type 2 diabetes. A 3-mg dose of the drug (Saxenda) is marketed for weight management in overweight or obese people who don't have type 2 diabetes.

In the second part of the study, 18 participants with type 2 diabetes were treated with either placebo or liraglutide for a total of 17 days; they then switched groups and repeated the experiment. Those in the intervention groups were given 0.6 mg of liraglutide for 7 days, 1.2 mg for 7 days, and 1.8 mg for 3 days.

The participants visited the laboratory four times over the period of the study; they stayed overnight during their visits in part so that the researchers could ensure that they fasted prior to the fMRI scans. Metabolic changes were recorded, and researchers studied neuroimaging responses to food cues.

Vegetarians and those with significant dietary restrictions were excluded, and a panel rated the images per group so that the results wouldn't be biased toward personal food preferences. The images were shown in random order, and nonfood cues, or pictures of objects, were included as a control.

The authors found that liraglutide decreased activation of the parietal cortex in response to highly desirable foods -- usually high in fat or sugar, like french fries, sodas, cakes, and cookies -- versus less desirable foods, like fruits and vegetables.

In a secondary analysis, the authors said that they observed decreased activation in the insula and putamen, both of which are involved in the brain's reward system. "But in humans, the control of eating is very complicated," Farr said. "It's not just one system, and people eat for many more reasons than just being hungry."

The research is very preliminary, but Farr said that her impression is that the cortical systems are most interesting when it comes to food regulation by the brain. Ratings of nausea correlated to decreased brain activation in the cingulate cortex, and there were no activations in the hypothalamus when viewing the images.

Limitations of the study include its small size and the inability to determine how much of the effect of GLP-1 on the brain impacted weight loss.

"It would be difficult to say without longer term studies how much weight loss it would account for," she emphasized.

"Future studies will be needed to confirm and extend these findings in larger samples of diabetics and/or with higher doses of liraglutide (3 mg) recently approved for obesity," the group concluded.

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