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New answers concerning a weight-regulating hormone

Date:
February 11, 2016
Source:
University of Copenhagen The Faculty of Health and Medical Sciences
Summary:
For years, scientists have failed to locate the DNA variants that control the weight-regulating hormone, leptin. However, new research has enabled the identification of four genes associated with leptin levels, which is particularly relevant within an obesity context. The study focuses on the powerful hormone leptin, which regulates humans' long-term energy balance by informing the brain about the amount of stored body fat.
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For years, scientists have failed to locate the DNA variants that control the weight-regulating hormone, leptin. However, new research has enabled the identification of four genes associated with leptin levels, which is particularly relevant within an obesity context. The study focuses on the powerful hormone leptin, which regulates humans' long-term energy balance by informing the brain about the amount of stored body fat.

Finding genes that cause fatness either by influencing our behavior or biology allows for a deeper understanding of why some people accumulate more fat than others. The research opens new avenues for treatments to counteract the genes that make us unhealthy.

The research has just been published in the science journal, Nature Communications.

Four new genes

"By studying the genetic code of over 50,000 men and women, we identified four genes associated with leptin levels," says Assistant Professor Tuomas Oskari Kilpeläinen from the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen who directed the study "Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels."

Leptin also influences our appetite. "It is produced when we are well fed, and it signals to the brain that there is plentiful energy and therefore reduces eating," adds Kilpeläinen.

Under normal conditions, leptin is generated by fat tissue, and the amount of leptin in the blood equals the total amount of fat tissue in the body. However, as long as 20 years ago, it was discovered that rare mutations in the leptin gene could cause extreme obesity. This happens if the mutation leads to a complete lack of the leptin hormone, which makes the patients constantly hungry, and therefore they gain weight quickly at a young age.

However, such cases are very rare. Normally, the leptin gene is very functional, but it depends on the individual in terms of how much leptin circulates in the blood -- people with equal levels of body fatness may have different leptin levels. These differences could affect our body weight and health, so it was important to look for genes that regulate leptin levels.

Global collaboration

The study used data from 36 different genetic studies and involved scientists at 146 institutions worldwide. To look for genes determining leptin levels in blood, the researchers examined the links between 2.5 million DNA variants and leptin levels.

"We found that the strongest DNA-variant associated with increased leptin levels was near the leptin gene itself, but we also found leptin-increasing variants near three other genes," says co-author Niels Grarup, Assistant Professor and Group Leader from the Section for Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research.

At a closer look, the DNA variants linked to leptin levels in the blood did not seem strongly associated with body weight. Some previous studies suggest that people with low leptin levels may be more sensitive to changes in leptin levels. More studies are needed to determine whether leptin-regulating variants may be important for appetite regulation in such individuals.


Story Source:

The above post is reprinted from materials provided by University of Copenhagen The Faculty of Health and Medical Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Tuomas O. Kilpeläinen, Jayne F. Martin Carli, Alicja A. Skowronski, Qi Sun, Jennifer Kriebel, Mary F Feitosa, Åsa K. Hedman, Alexander W. Drong, James E. Hayes, Jinghua Zhao, Tune H. Pers, Ursula Schick, Niels Grarup, Zoltán Kutalik, Stella Trompet, Massimo Mangino, Kati Kristiansson, Marian Beekman, Leo-Pekka Lyytikäinen, Joel Eriksson, Peter Henneman, Jari Lahti, Toshiko Tanaka, Jian’an Luan, Fabiola Del Greco M, Dorota Pasko, Frida Renström, Sara M. Willems, Anubha Mahajan, Lynda M. Rose, Xiuqing Guo, Yongmei Liu, Marcus E. Kleber, Louis Pérusse, Tom Gaunt, Tarunveer S. Ahluwalia, Yun Ju Sung, Yolande F. Ramos, Najaf Amin, Antoinette Amuzu, Inês Barroso, Claire Bellis, John Blangero, Brendan M. Buckley, Stefan Böhringer, Yii-Der I Chen, Anton J. N. de Craen, David R. Crosslin, Caroline E. Dale, Zari Dastani, Felix R. Day, Joris Deelen, Graciela E. Delgado, Ayse Demirkan, Francis M. Finucane, Ian Ford, Melissa E. Garcia, Christian Gieger, Stefan Gustafsson, Göran Hallmans, Susan E. Hankinson, Aki S Havulinna, Christian Herder, Dena Hernandez, Andrew A. Hicks, David J. Hunter, Thomas Illig, Erik Ingelsson, Andreea Ioan-Facsinay, John-Olov Jansson, Nancy S. Jenny, Marit E. Jørgensen, Torben Jørgensen, Magnus Karlsson, Wolfgang Koenig, Peter Kraft, Joanneke Kwekkeboom, Tiina Laatikainen, Karl-Heinz Ladwig, Charles A. LeDuc, Gordon Lowe, Yingchang Lu, Pedro Marques-Vidal, Christa Meisinger, Cristina Menni, Andrew P. Morris, Richard H. Myers, Satu Männistö, Mike A. Nalls, Lavinia Paternoster, Annette Peters, Aruna D. Pradhan, Tuomo Rankinen, Laura J. Rasmussen-Torvik, Wolfgang Rathmann, Treva K. Rice, J Brent Richards, Paul M. Ridker, Naveed Sattar, David B. Savage, Stefan Söderberg, Nicholas J. Timpson, Liesbeth Vandenput, Diana van Heemst, Hae-Won Uh, Marie-Claude Vohl, Mark Walker, Heinz-Erich Wichmann, Elisabeth Widén, Andrew R. Wood, Jie Yao, Tanja Zeller, Yiying Zhang, Ingrid Meulenbelt, Margreet Kloppenburg, Arne Astrup, Thorkild I. A. Sørensen, Mark A. Sarzynski, D. C. Rao, Pekka Jousilahti, Erkki Vartiainen, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Eero Kajantie, Clive Osmond, Aarno Palotie, Johan G. Eriksson, Markku Heliövaara, Paul B. Knekt, Seppo Koskinen, Antti Jula, Markus Perola, Risto K. Huupponen, Jorma S. Viikari, Mika Kähönen, Terho Lehtimäki, Olli T. Raitakari, Dan Mellström, Mattias Lorentzon, Juan P. Casas, Stefanie Bandinelli, Winfried März, Aaron Isaacs, Ko W. van Dijk, Cornelia M. van Duijn, Tamara B. Harris, Claude Bouchard, Matthew A. Allison, Daniel I. Chasman, Claes Ohlsson, Lars Lind, Robert A. Scott, Claudia Langenberg, Nicholas J. Wareham, Luigi Ferrucci, Timothy M. Frayling, Peter P. Pramstaller, Ingrid B. Borecki, Dawn M. Waterworth, Sven Bergmann, Gérard Waeber, Peter Vollenweider, Henrik Vestergaard, Torben Hansen, Oluf Pedersen, Frank B. Hu, P Eline Slagboom, Harald Grallert, Tim D. Spector, J.W. Jukema, Robert J. Klein, Erik E Schadt, Paul W. Franks, Cecilia M. Lindgren, Rudolph L. Leibel, Ruth J. F. Loos. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels. Nature Communications, 2016; 7: 10494 DOI: 10.1038/ncomms10494

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University of Copenhagen The Faculty of Health and Medical Sciences. "New answers concerning a weight-regulating hormone." ScienceDaily. ScienceDaily, 11 February 2016. <www.sciencedaily.com/releases/2016/02/160211104805.htm>.
University of Copenhagen The Faculty of Health and Medical Sciences. (2016, February 11). New answers concerning a weight-regulating hormone. ScienceDaily. Retrieved July 23, 2016 from www.sciencedaily.com/releases/2016/02/160211104805.htm
University of Copenhagen The Faculty of Health and Medical Sciences. "New answers concerning a weight-regulating hormone." ScienceDaily. www.sciencedaily.com/releases/2016/02/160211104805.htm (accessed July 23, 2016).

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