Holmstroem 2013 Metabolism
|Holmström MH, Tom RZ, Björnholm M, Garcia-Roves PM, Zierath JR (2013) Effect of leptin treatment on mitochondrial function in obese leptin-deficient ob/ob mice. Metabolism 62:1258-67.|
Abstract: Leptin stimulates peripheral lipid oxidation, but the influence on mitochondrial function is partly unknown. We investigated tissue-specific mitochondrial function in leptin-deficient obese C57BL/6J-ob/ob mice compared to lean littermates following leptin treatment.
Lean and obese ob/ob mice were treated with saline or leptin for 5days. At day six, liver, extensor digitorum longus (EDL) and soleus muscle were dissected and mitochondrial respiration analyzed in freshly dissected tissues. Expression of key proteins in the regulation of mitochondrial function was determined.
In liver, mitochondrial respiration was reduced in ob/ob mice compared to lean mice. Expression of mitochondrial transcription factor A (TFAM) was decreased in ob/ob mice, but increased with leptin treatment. In glycolytic EDL muscle, mitochondrial respiration was increased in ob/ob mice. Protein markers of complex II, IV and ATP synthase were increased in EDL muscle from both saline- and leptin-treated ob/ob mice. TFAM protein abundance was decreased, while dynamin-1-like protein was increased in EDL muscle from saline-treated ob/ob mice and restored by leptin treatment. In oxidative soleus muscle, mitochondrial respiration and electron transport system protein abundance were unchanged, while TFAM was reduced in ob/ob mice.
In conclusion, leptin-deficient ob/ob mice display tissue-specific mitochondrial adaptations under basal conditions and in response to leptin treatment. Mitochondrial respiration was decreased in liver, increased in glycolytic muscle and unaltered in oxidative muscle from ob/ob mice. Insight into the tissue-specific regulation of mitochondrial function in response to energy supply and demand may provide new opportunities for the treatment of insulin resistance.
• Keywords: Leptin, Mitochondria, Skeletal Muscle Metabolism, Liver, Therapy Intervention
Labels: MiParea: Respiration, Genetic knockout;overexpression Pathology: Diabetes, Obesity
Organism: Mouse Tissue;cell: Skeletal muscle, Liver Preparation: Permeabilized tissue