Obese individuals have relatively fewer Type I fibres compared to average-weight counterparts and Type I fibres are believed to confer resistance to obesity. Consistent with this, the numbers of Type I fibres decrease in response to inactivity and or a high-fat diet (HFD). Conversely, numbers of Type I fibres increase in response to exercise.
Researchers at Yale University School of Medicine have now identified MAPK phosphatase-1 (MKP-1) as a key player in the Type I/Type II shift in response to HFD. The group had previously shown that mice deficient in MKP-1 displayed increased energy expenditure and were resistant to diet-induced obesity. This new study, published in the Journal of Clinical Investigation, found that MKP-1 was overexpressed in skeletal muscle of mice in response to excess dietary fat.
MKP-1 dephosphorylates, and consequently deactivates, MAP kinases in the nucleus. In the study, MKP-1 overexpression reduced p38 MAPK-mediated phosphorylation of PPARγ coactivator 1α (PGC-1α), which plays a central role in maintaining levels of Type I myofibres. The phosphorylation of PGC-1α is believed to stabilise the protein and, consistent with this, MKP-1 deficient mice had higher levels of PGC-1α in skeletal muscle than did wild-type mice and were refractory to the loss of Type I myofibres when fed a high-fat diet.