Researchers at the Salk Institute for Biological Studies have developed a compound that targets the farnesoid X receptor (FXR) in the intestines and may help to reduce diet-induced weight gain, body-wide inflammation, and hepatic glucose production while enhancing thermogenesis and browning of white adipose tissue (WAT). The FXR antagonist is described in a new study published in the journal Nature Medicine.

FXR, a protein that is involved in the body’s release of bile acids from the liver, digestion of food, and storage of fats and sugars, has been the target of previous research using systemic drugs to activate FXR but these drugs usually affect several organs with a range of side effects. The scientists at the Salk Institute created a fexaramine compound that is not transported into the bloodstream and only reaches the intestines, limiting potential side effects and boosting the efficacy of the compound.

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In the study, obese mice were administered fexaramine in pill form daily once a day for five weeks; after this time, the mice stopped gaining weight and had reduced body fat, blood sugar, and cholesterol levels vs. the control mice. The mice treated with fexaramine also exhibited an increase in body temperature, signaling an increase in metabolism, and some browning of WAT.

Ronald Evans, senior author of the paper, calls the compound an “imaginary meal” because it creates a similar reaction in the body as if it has consumed calories, without eating. The researchers are preparing for human clinical trials to test the effectiveness of fexaramine to treat obesity and metabolic disease.

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