title: Effect of leptin treatment on mitochondrial function in obese leptin-deficient ob/ob mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Lean and obese ob/ob mice were treated with saline or leptin for 5 days. 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria H
authors.initials: MH
authors.lastname: Holmström
authors.forename: Robby Zachariah
authors.initials: RZ
authors.lastname: Tom
authors.forename: Marie
authors.initials: M
authors.lastname: Björnholm
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Garcia-Roves
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006019:Glycolysis; D020738:Leptin / Q000172:deficiency / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D009928:Organ Specificity; D010085:Oxidative Phosphorylation
chemical_list: D020738:Leptin
keywords: 2-(N-morpholino)ethanesulfonic acid; AMP-activated protein kinase; AMPK; ATP synthase subunit beta; ATP5B; BIOPS; BSA; C; Complex; DNM1L; EDL; ETS; FCCP; Leptin; Liver; MES; MFN2; MRI; MTCO1; MiR05; Mitochondria; NADH-dehydrogenase 1 alpha subcomplex subunit 9; NADP; NDUFA9; OPA1; PEPCK; PPARα; PVDF; SDHA; Skeletal Muscle Metabolism; TBST; TFAM; Therapy Intervention; Tris-buffered saline with 0.1% Tween-20; UQCRC1; biopsy preservation solution; bovine serum albumin; carbonylcyanide-4-(trifluoromethoxy)-phenyl-hydrazone; cytochrome b-c1 complex subunit 1; cytochrome c oxidase subunit 1; dynamin-1-like protein; dynamin-like 120 kDa protein; electron transport system; extensor digitorum longus; magnetic resonance imaging; mitochondrial respiration medium; mitochondrial transcription factor A; mitofusin-2; nicotinamide adenine dinucleotide phosphate; peroxisome proliferator-activated receptor alpha; phosphoenolpyruvate carboxykinase; polyvinyl difluoride; succinate dehydrogenase flavoprotein subunit