White Fat May Be Converted Into Energy Burning Brown Fat

Susanne Mandrup Professor, Department of Biochemistry and Molecular Biology Odense M · DenmarkMedicalResearch.com Interview with:
Susanne Mandrup
Professor, Department of Biochemistry and Molecular Biology
Odense M · Denmark

Medical Research: What is the background for this study? What are the main findings?

Prof. Mandrup: Obesity affects more than 1 billion adults globally and represents one of the greatest current threats to human health. Paradoxially, the fat tissues in the human body that stores excess calories might hold the key for a future obesity treatment.

Most human fat depots are white fat tissues that store energy as fat; however, humans also have small amounts of brown fat, which primarily acts as an effective fat burner for the production of heat. Recent studies have shown that it is possible to “brown” white fat tissues (e.g. by prolonged cold-exposure) leading to an increase in the energy consumption of the body. The challenge is to understand how energy storing white fat cells are reprogrammed into so-called “brite” (brown-in-white) fat cells in the white adipose tissue and thus make adipose tissue burn off excess energy as heat instead of storing it.

In this study we have for the first time investigated how the genome of white fat cells is reprogrammed during browning. We stimulated browning in human white adipocytes by a drug used to treat type II diabetes and compared white and “brite” fat cells. This showed that “brite” fat cells have distinct gene programs which, when active, make these cells particularly energy-consuming. Furthermore, we identified an important factor in the browning process – the gene regulatory protein KLF11 (Kruppel Like Factor-11).

Medical Research: What should clinicians and patients take away from your report?

Prof. Mandrup: We have obtained a greater insight into the molecular mechanism that control browning of white fat cells. Being able to control the formation and activation of brite adipocytes from white fat cells constitutes a potential strategy for future treatment of obesity.

Medical Research: What recommendations do you have for future research as a result of this study?

Prof. Mandrup: We should focus on getting an even better understanding of the browning process and the factors involved. Such research will provide potential drug targets that can be used to increase brite fat cell mass and function in humans.

Citation:
“Browning of human adipocytes requires KLF11 and reprogramming of PPAR super-enhancers”, “Genes and Development” , 1 January 2015; Vol. 29, No. 1

Anne Loft1, Isabel Forss1*, Majken Storm Siersbæk1*, Søren Fisker Schmidt1, Ann-Sofie Bøgh Larsen1, Jesper Grud Skat Madsen1,5, Didier Pisani4, Ronni Nielsen1, Mads Malik Aagaard1, Angela Mathison2, Matt J. Neville3, Raul Urrutia2, Fredrik Karpe3, Ez-Zoubir Amri4, Susanne Mandrup1#