Press and Public Relations

Cortisol Controls Recycling of Bile Acids - Mice without cortisol receptor lose weight and suffer from gallstones

No. 34 | 06/07/2011 | by (Koh)

Scientists of the German Cancer Research Center (DKFZ) have made a discovery in mice whose liver cells are unable to receive cortisol signals: This hormone is responsible for a process in which the liver recycles bile acids from the blood. If this recycling is disrupted, the animals develop gallstones and lose weight because they are no longer able to digest dietary fats. They also use more energy for heat production. The researchers assume that regulation of recycling serves the purpose of conserving energy efficiently in times of need.

Three-dimensional image of a liver with blood vessels (red and blue), bile ducts and gallbladder (green). Source: Prof. Dr. Hans-Peter Meinzer, Deutsches Krebsforschungszentrum
© dkfz.de

Nature sees to it that we do not have “too much choler” (bile) in our body. A delicately equilibrated regulation system ensures that there is always exactly the right amount of bile in the gallbladder. When we are hungry, our body releases a hormone called cortisol, which is a glucocorticoid. Hepatic cells receive this hormone signal through their cortisol receptors (glucocorticoid receptors) and respond by filling the gallbladder with bile in preparation of the imminent food intake. Directly upon eating a meal, bile is secreted into the intestine.

Bile acids contained in bile are indispensable for fat digestion. They emulsify fats into minute droplets, which can be broken down. Our body recovers 95 percent of bile acids from the bowel contents. They are reabsorbed by cells of the intestinal mucosa and transported back to the liver via the blood.

“We have now found out that this recycling process is controlled by the cortisol hormone,” says Dr. Stephan Herzig. Herzig is head of the Division of Molecular Metabolic Control – a joint research department of the German Cancer Research Center (DKFZ), the Center for Molecular Biology (ZMBH) of Heidelberg University, and Heidelberg University Hospitals. The research group has published its results in the journal Cell Metabolism. To obtain proof of cortisol’s key role in bile acid recycling, the investigators used mice whose hepatic cells specifically lack the cortisol receptor. That means that cortisol signals are not received in the liver. When the modified animals were hungry, their bile contained considerably less bile acid than that of normal animals. This also led to a reduced solubility of cholesterol in the gallbladder so that an increased amount of gallstones developed. Compared to animals with intact cortisol receptor, the genetically modified mice lost weight, because they excreted fats contained in the food without digesting or using them.

The investigators also found out what causes acid levels in the bile to be reduced: In the genetically manipulated animals, transport proteins used by hepatic cells to recover bile acids from the blood have a reduced performance. As a result, bile acids remain in the blood in these mice. In the blood, however, bile acids have a hormone-like effect on various tissues. Among other things, they stimulate brown fat tissue to increase heat production.

In order to find out whether cortisol signals have an effect on bile acid recycling in humans as well, the Heidelberg scientists studied blood samples of patients suffering from a rare condition called Addison’s disease. When people are affected by this disease, their immune system destroys the adrenal gland, which produces cortisol. Patients therefore suffer from a lack of cortisol. In blood samples taken from patients before and after meals, the investigators discovered that bile acid recycling in the liver is disrupted without cortisol in humans, too.

Stephan Herzig has an idea of the possible biological purpose of the precise regulation of bile acid recycling: “The moving back of bile acid in a state of hunger is useful for protecting the body from wasting energy in times of need. If the level of bile acids in the blood is reduced under the influence of cortisol, brown fat tissue produces less heat – the body saves its energy reserves for vital functions. At the same time, this mechanism prevents gallstones from forming and ensures efficient energy intake in the intestine.”

The project was conducted in the framework of the DKFZ-ZMBH Alliance, a strategic collaboration of DKFZ and ZMBH as part of Heidelberg University’s “Concept for the Future” in the German government’s Excellence Initiative.

A picture for this press release is available on the Internet at:
http://www.dkfz.de/de/presse/pressemitteilungen/2011/images/Liver.jpg

Figure legend: Three-dimensional image of a liver with blood vessels (red and blue), bile ducts and gallbladder (green). Source: Prof. Dr. Hans-Peter Meinzer, Deutsches Krebsforschungszentrum

Adam J. Rose, Mauricio Berriel Díaz, Anja Reimann, Johanna Klement, Tessa Walcher, Anja Krones-Herzig, Oliver Strobel, Jens Werner, Achim Peters, Anna Kleyman, Jan P. Tuckermann, Alexandros Vegiopoulos and Stephan Herzig: Molecular control of systemic bile acid homeostasis by the liver glucocorticoid receptor. Cell Metabolism, 2011, DOI 10.1016/j.cmet.2011.04.010

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

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