INVOLVEMENT OF ECTOPIC FAT AND MITOCHONDRIAL FUNCTION IN TYPE 2 DIABETES
Event details
| Date | 08.11.2010 |
| Hour | 12:15 |
| Speaker | Dr Patrick Schrauwen, Dept. of Human Biology, Maastricht University Medical Center, Maastricht, The Netherlands |
| Location |
SV1717a
|
| Category | Conferences - Seminars |
Obesity is the major risk factor for the development of type 2 diabetes mellitus. In obesity, fat not only stores in white adipose tissue, but fatty acids can also accumulate in ectopic fat stores like heart, liver and muscle. Fat accumulation in skeletal muscle is strongly associated with the development of skeletal muscle insulin resistance, and the latter is a first hallmark in the development of type 2 diabetes mellitus. In the recent 5-6 years, a reduced mitochondrial function in skeletal muscle has been proposed to underlie the accumulation of fat in skeletal muscle. In fact, non-invasive in vivo magnetic resonance spectroscopy has revealed a reduced mitochondrial function combined with elevated muscular lipid content in type 2 diabetic patients and in pre-diabetic first-degree relatives. Ex vivo measurements have pointed towards reduced intrinsic mitochondrial function, reductions in mitochondrial density and alterations in mitochondrial structure. It is indeed tempting to suggest that these mitochondrial abnormalities could be responsible for the accumulation of fat in muscle and thereby be linked to the development of insulin resistance. Alternatively, however, mitochondrial dysfunction may be the consequence of insulin resistance and/or muscular fat accumulation. Thus, the acute elevation of circulating fatty acids reduces the expression of the transcriptional co-activator PGC1, an important transcription factor in mitochondrial biogenesis. Furthermore, fatty acids that accumulate in skeletal muscle cells may exert deleterious effects to mitochondrial function (lipotoxicity) via the formation of ROS-induced lipid peroxides. Indeed, increased lipid peroxidation has been reported in insulin resistant skeletal muscle. In addition, studies performed in animals fed high-fat diets tend to indicate that muscular fat accumulation precedes the development of mitochondrial dysfunction. In this presentation the current evidence for the role of mitochondrial dysfunction in the etiology of muscular insulin resistance will be discussed. Furthermore, it will be discussed if endurance training can reverse mitochondrial dysfunction.
Practical information
- General public
- Free