Just where fat is deposited in the body and to what degree a person may benefit from a lifestyle intervention depends, among other things, on how sensitive the brain is to insulin. If the person’s brain responds sensitively to the hormone, a significant amount of weight can be lost, unhealthy visceral fat reduced, and the weight loss can be maintained over the long term. However, If the person’s brain responds only slightly or not at all to insulin, the person only loses some weight at the beginning of the intervention and then experiences weight regain. Over the long term, the visceral fat also increases. These are the results of a long-term study by the German Center for Diabetes Research (DZD), Helmholtz Zentrum München and Tübingen University Hospital which has now been published in Nature Communications.

To which extent body fat has an unhealthy effect depends primarily on where it is stored. If fat accumulates in the abdomen, this is particularly unfavorable. This is because the visceral fat releases numerous neurotransmitters that affect blood pressure, influence the secretion of the hormone insulin and can cause inflammation. This increases the risk of diabetes, cardiovascular disease and certain types of cancer. The subcutaneous fat which accumulates on the buttocks, thighs and hips has no adverse health effects.

However, it is still unclear why fat storage does not occur in the same place in all people. Studies in the Tübingen Lifestyle Intervention Program (TULIP) which was started over 10 years ago under the direction of Prof. Hans-Ulrich Häring [1] suggest that brain insulin responsiveness could play an important role here. They showed that people with a high insulin sensitivity in the brain benefit significantly more from a lifestyle intervention with a diet rich in fiber and exercise than people with insulin resistance in the brain. Not only did they lose more weight, they also had a healthier fat distribution.

But how does insulin sensitivity affect the distribution of body fat and weight in the long term? Researchers from the German Center for Diabetes Research (DZD), Helmholtz Zentrum München and Tübingen University Hospital investigated this question in a long-term study. For this purpose, they recorded the follow-up data of 15 participants over a period of nine years, in which the insulin sensitivity in the brain was determined by magnetoencephalography before the start of a 24-month lifestyle intervention.

High insulin sensitivity associated with reduction in visceral fat and weight
It was found that insulin action in the brain not only determines body weight, but also the distribution of fat in the body. “Subjects with high insulin sensitivity in the brain benefited from the lifestyle intervention with a pronounced reduction in weight and visceral fat. Even after the lifestyle intervention had ended, they only regained a small amount of fat during the nine-year follow-up,“  said the head of the study, Professor Martin Heni from Tübingen University Hospital. In contrast, people with brain insulin resistance only showed a slight weight loss in the first nine months of the program. "Afterwards, their body weight and visceral fat increased again during the following months of lifestyle intervention," said first author PD Dr. Stephanie Kullmann.

Since the insulin action in the hypothalamus is crucial for the regulation of peripheral energy metabolism, the researchers also investigated how insulin sensitivity in this area of the brain is related to the distribution of body fat. For this purpose, they examined a cross-sectional cohort of 112 participants. The analysis of the data showed that people with high insulin sensitivity in the hypothalamus form little visceral fat. However, insulin sensitivity has no influence on the mass of subcutaneous fat.  

Our study reveals a novel key mechanism that regulates fat distribution in humans. Insulin sensitivity in the brain determines where fat is deposited, ”said Heni, summarizing the results. Since visceral fat not only plays a role in the development of type 2 diabetes, but also increases the risk of cardiovascular disease and cancer, the study results may also open up new approaches for treatment options beyond metabolic diseases. The researchers in Tübingen are already working on new therapies to abolish insulin resistance in the brain and thus have a beneficial effect on body fat distribution.

Original publication:
Kullmann et al. (2020): Brain insulin sensitivity is linked to adiposity and body fat distribution. Nature Communications, DOI: doi.org/10.1038/s41467-020-15686-y

1) Tschritter, O. et al. High cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention. Diabetologia 55, 175–182 (2012).

Scientific contact:
Prof. Dr. med. Martin Heni
Tübingen University Hospital, Internal Medicine IV
Otfried Müller Straße 10
72076 Tübingen
Phone: +49 (0)7071 29-82714
Email: martin.heni(at)med.uni-tuebingen.de

The German Center for Diabetes Research (DZD) e.V. is one of six German Centers for Health Research. It brings together experts in the field of diabetes research and combines basic research, epidemiology and clinical application. By adopting an innovative, integrative approach to research, the DZD aims to make a substantial contribution to the successful, personalized prevention, diagnosis and treatment of diabetes mellitus. The members of the association are Helmholtz Zentrum München - German Research Center for Environmental Health, the German Diabetes Center (DDZ) in Düsseldorf, the German Institute of Human Nutrition (DIfE) in Potsdam-Rehbrücke, the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Zentrum München at the University of Tübingen, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of TU Dresden, associated partners at the universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich, and other project partners. Further information: www.dzd-ev.de/en

As German Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the diagnosis, therapy and prevention of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The head office of the center is located in Neuherberg to the north of Munich. Helmholtz Zentrum München has approximately 2300 staff members and is a member of the Helmholtz Association, a German research organization comprised of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. www.helmholtz-muenchen.de/en

Founded in 1805, Tübingen University Hospital is one of the leading centers of German university medicine. As one of the 33 university hospitals in Germany, it contributes to the successful combination of high-performance medicine, research and teaching. Well over 400,000 inpatients and outpatients from all over the world benefit annually from this combination of science and practice. The clinics, institutes and centers unite all specialists under one roof. The experts work together across disciplines and offer every patient optimal treatment based on the latest research results. Tübingen University Hospital conducts research for better diagnoses, therapies and chances of cure, many new treatment methods are clinically tested and applied here. Neurosciences, oncology, immunology, infection research, vascular medicine and diabetes research are the main areas of research in Tübingen. The University Hospital is a reliable partner in four of the six German Centers for Health Research initiated by the German government. www.medizin.uni-tuebingen.de/en