Nav: Home

The Lypla1 gene impacts obesity in a sex-specific manner

February 15, 2019

Susceptibility to obesity, insulin resistance and other cardio-metabolic traits may also be dependent on a person's sex. An international research team of the University of California (UCLA), Helmholtz Zentrum München, a partner of the DZD, and Ludwig-Maximilians-Universität München studied sex differences and sex-specific interaction with the genetic background in cardio-metabolic phenotypes. The researchers discovered, among other things, a sex-specific obesity locus of the Lypla1 gene, which is associated with human obesity. The results of the study have now been published in Cell Metabolism.

Men and women may be differently susceptible to obesity, insulin resistance, and other cardio-metabolic traits. Women often have more advantageous metabolic profiles. This has been described for mice but also for humans. But how does sex interact with genes? What role does natural genetic variance play? And how does this affect the development of cardio-metabolic traits? In order to answer these questions, an international team of researchers used an animal model (hybrid mouse diversity panel) to search for sex-specific differences in 50 cardio-metabolic traits. The effect of sex on cardio-metabolic traits was investigated in terms of sex-specific correlations with specific disease phenotypes, their genetic architecture and the underlying expression networks in fat and liver. It was found that sex - depending on the genetic background - plays a role in gene expression and the development of cardio-metabolic traits. The research team discovered a sex-specific obesity locus for the Lyplal1 gene.

"In addition, we were able to show that there is sex-specific regulation for the "beiging" of white adipose tissue* and sex-specific interactions for mitochondrial function," said UCLA Professor Aldons J. Lusis, last author and head of the study. The study showed that females have a higher mitochondrial activity and produce more brown adipose tissue ("beiging"). This reduces fat mass and insulin resistance. In males, the interaction between genes and sex tends to lead to low mitochondrial activity and low beiging. Weight and insulin resistance increase.

"In the reference literature there are already indications of major differences in adipose biology between sexes also in humans. This study provides insights into the depth and breadth of sex differences in metabolism. We believe that our results provide compelling evidence as to why males and females in biological research should be treated as distinct organisms as a whole, rather than attempting to reconcile these differences one molecule at a time," said DZD researcher Professor Susanna Hofmann, MD of the Institute for Diabetes and Regenerative Research of the Helmholtz Diabetes Center. Her group, together with Professor Axel Walch from the Core Facility Pathology & Tissue Analytics at Helmholtz Zentrum München, examined the adipose tissue and analyzed the sex differences in the browning of white adipose tissue.

There are still many gaps in our understanding of the biology underlying these sex-specific differences. As a long-term goal, the researchers therefore want to develop a biological network model that describes the differences between men and women (the ''sex-ome'') at system level. Such a model will require identifying the primary and downstream sex-biased factors that act on the network and understanding how the sex-biased network interactions give rise to sex differences in the emergent phenotypes.

*Beiging (browning)

Brown adipose tissue can produce heat through the oxidation of fatty acids. This takes place in numerous mitochondria, which are also responsible for the brownish coloration of the tissue. If the "good" brown fat is activated, the metabolism is stimulated and the "bad" white fat deposits are reduced. The occurrence of brown or beige adipocytes in white adipose tissue is called browning or beiging, a phenomenon associated with increased energy consumption and, at least in the mouse model, with protection against obesity.
-end-
Original Publication: Norheim et al., (2019): Gene-by-Sex Interactions in Mitochondrial Functions and Cardio-Metabolic Traits. Cell Metabolism, DOI: 10.1016/j.cmet.2018.12.013

Scientific Contact:

University Professor Susanna Hofmann, MD
Helmholtz Diabetes Center
Institute for Diabetes and Regeneration Research
Helmholtz Zentrum München
German Research Center for Environmental Health, GmbH
Ingolstädter Landstrasse 1
85764 Neuherberg
Germany
Phone: ++49-89-3187-2112
e-mail: susanna.hofmann@helmholtz-muenchen.den:

Deutsches Zentrum fuer Diabetesforschung DZD

Related Obesity Articles:

Obesity is in the eye of the beholder
Doctors have a specific definition of what it means to be overweight or obese, but in the social world, gender, race and generation matter a lot for whether people are judged as 'thin enough' or 'too fat.'
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
Three in 4 don't know obesity causes cancer
Three out of four (75 percent) people in the UK are unaware of the link between obesity and cancer, according to a new Cancer Research UK report published today.
Obesity on the rise in Indonesia
Obesity is on the rise in Indonesia, one of the largest studies of the double burden of malnutrition in children has revealed.
Obesity rates are not declining in US youth
A clear and significant increase in obesity continued from 1999 through 2014, according to an analysis of data on United States children and adolescents age 2 to 19 years.
How does the environment affect obesity?
Researchers will be examining how agricultural and food processing practices may affect brown fat activity directly or indirectly.
Obesity Day to highlight growing obesity epidemic in Europe
The growing obesity epidemic, which is predicted to affect more than half of all European citizens by 2030, will be the focus of European Obesity Day to be held on May 21.
Understanding obesity from the inside out
Researchers developed a new laboratory method that allowed them to identify GABA as a key player in the complex brain processes that control appetite and metabolism.
Epigenetic switch for obesity
Obesity can sometimes be shut down.
Immunological Aspects of Obesity
This FASEB Conference focuses on the interactions between obesity and immune cells, focusing in particular on how inflammation in various organs influences obesity and obesity-related complications.

Related Obesity Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...