Genetic and biophysical investigation of the relationship between muscle characteristics and obesity
Obesity, which is an increasing incidence worldwide, produces many disorders such as insulin resistance, hypertension, hyperlipidemia, cardiovascular disorders and is the major cause generation of metabolic syndrome. Insulin resistance is the inability of insulin to exert its action on the periphery such as skeletal muscle and adipose tissue. Although there are some proposed mechanisms, the underlying mechanism of the generation of whole body insulin resistance remains unclear. Skeletal muscles, being responsible for the majority of insulin-mediated glucose disposal, comprises the major site of insulin resistance in obesity and type 2 diabetes mellitus. The mechanism of generation of insulin resistance is not totally understood. One proposed mechanism is that intramyocellular lipid (IMCL) accumulation plays a role in the generation of insulin resistance in muscles. Recent evidence points out that the determination of the localization of lipid accumulation in muscle tissues is an important determinant of obesity induced insulin resistance. In this study, the characterization of M. longissimus dorsi and Quadriceps muscles of 15 different mice strains of genetic model of obesity will be performed based on compositional, structural, functional and dynamical properties of their macromolecules. Moreover, the sites of macromolecular accumulation and the properties of these macromolecules will be determined. Furthermore, the genotypic and phenotypic characterization of the muscles of mouse strains will be performed. With the combination of the genetic and biophysical data, 15 different obese mouse strains will be differentiated regarding their muscle tissue properties.
The results of this proposed project
1. will review the relation between muscle macromolecular characteristics and obesity,
2. will generate a spectral database of skeletal muscles in obesity, some of which can be used as biosensors,
3. will support valuable information for generation of a new biosensor based approach in early diagnosis of insulin resistance
4. will help to clarify unidentified mechanism of insulin resistance in skeletal muscle and gain better insight into the genetic basis of obesity, and the information obtained can be transferred for the use in treatment of human patients in future.
Brockmann, Gudrun A. Prof. Dr. habil. rer. nat. (Details) (Breeding Biology and Molecular Animal Breeding)
Financer
BMBF
Duration of project
Start date: 01/2009
End date: 03/2012
Research Areas
Muskel, Insulinresistenz, Fettleibigkeit, FTIR, Marker
