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Ozgene at ICI2016
The epic of type 2 diabetes
Almost 90% of people with type 2 diabetes are overweight or obese. However, not all obese individuals develop the disease. Changes in the epigenome could be a fundamental reason behind the susceptibility to type 2 diabetes. The epigenome is involved in regulating gene expression by coupling chemical flags to the DNA and to the histone proteins that constitute chromatin. While the genome itself remains quite static, the epigenome can be dynamically altered by environmental conditions and nutritional components.
Dr Eckardt Treuter from the Karolinska Institutet in Sweden and Dr Nicolas Venteclef from Institute of Health and Medical Research (INSERM) in France have studied alterations of the epigenome during the development of obesity as a possible trigger to insulin resistance and diabetes.
In a recent paper published in Nature Medicine, Drs Treuter and Venteclef found that the variation in type 2 diabetes development may relate to adipose tissue (AT) inflammation that develops as obesity progresses. The degree of AT inflammation is linked to the state of macrophage activation and driven by epigenomic alterations linked to gene expression. The paper demonstrates that a co-repressor complex containing G protein pathway suppressor 2 (GPS2) plays a key role in controlling the epigenome in macrophages as well as in adipocytes.
Obese individuals with diabetes show reduced GPS2 expression in macrophages as well as elevated systemic and AT inflammation. A macrophage- and adipocyte-specific Gps2 knockout mice, derived from floxed mice generated by Ozgene, were used to study this causality further. The mice were put on a high-fat diet, but instead of becoming obese, they developed complications such as adipose tissue inflammation, systemic insulin resistance, and fatty liver more rapidly than normal mice.
The mouse study showed that the inappropriate Gps2 gene expression influenced the function of the co-repressor complex, to the extent of adipose tissue inflammation and systemic insulin resistance. Interestingly, transplantation of bone marrow overexpressing GPS2 reduced inflammation and improved insulin sensitivity, revealing a potentially reversible disease mechanism.
Drs Treuter and Venteclef believe that alterations of the epigenome can speed up an inflammatory response under conditions of metabolic stress linked to obesity and diabetes. Their findings indicate that these alterations during the development of obesity may not just be a consequence, but a cause of insulin resistance and diabetes.
For more information on the research, please visit the Karolinska Institutet website and see the recent publication below.
For more information on Ozgene mouse models, please see Ozgene services.
Ozgene at ICI2016
Our CEO and CSO, Dr Frank Koentgen and Dr Gabi Suess, are attending the ICI2016 conference in Melbourne 21-26 August. Please let us know if you would like to have a chat with Frank and Gabi during the conference.
FEATURED - Nat Med. 2016 Jul 22.
Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.
Fan R, Toubal A, Goñi S, Drareni K, Huang Z, Alzaid F, Ballaire R, Ancel P, Liang N, Damdimopoulos A, Hainault I, Soprani A, Aron-Wisnewsky J, Foufelle F, Lawrence T, Gautier JF, Venteclef N, Treuter E. - Karolinska Institutet, Sweden. Sorbonne Universités, Université Pierre et Marie-Curie, INSERM, Institute of Cardiometabolism and Nutrition, Clinique Geoffroy Saint-Hilaire, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière, Lariboisière Hospital, University Paris-Diderot, Paris, France. INSERM, Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, Marseille, France. [read]
J Exp Med. 2016 Jul 25.
DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes.
Maul RW, MacCarthy T, Frank EG, Donigan KA, McLenigan MP, Yang W, Saribasak H, Huston DE, Lange SS, Woodgate R, Gearhart PJ. - National Institute on Aging, NIH, Baltimore, MD; State University of New York, Stony Brook, NY; National Institute of Child Health and Human Development, NIH, Rockville, MD; University of Texas MD Anderson Cancer Center Science Park, Smithville, TX, USA. [read]
Sci Rep. 2016 Jun 30.
Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice.
Philp LK, Day TK1 Butler MS, Laven-Law G, Jindal S, Hickey TE, Scher HI, Butler LM, Tilley WD. - Faculty of Health Sciences, University of Adelaide, Australia. Memorial Sloan Kettering Cancer Center, NY, USA. [read]
Frank's blog: Curiosity
I have recently found that many aspects of my life have been leading to one discovery… curiosity. But what does curiosity actually mean? This might get quite heavy so just bear with me...
When all processes produce the desired result first time, the timeline can be as short as 18 weeks.
Our fastest conditional KO project took 20 weeks from vector construction to germline transmission.
The Simple Moving Average timeline of our recently completed conditional KO projects is 31 weeks.