Axelrod 2019 Abstract IOC141

From Bioblast
Axelrod CL, Davuluri G, Zunica ERM, Noland RC, Hoppel CL, Kirwan JP (2019) Administration of BAM15 to obese C57BL/6J mice increases skeletal muscle fatty acid oxidation independent of OXPHOS or ETC capacity. Mitochondr Physiol Network 24.02.

Link: IOC141

Axelrod CL, Davuluri G, Zunica ERM, Noland RC, Hoppel CL, Kirwan JP (2019)

Event: IOC141

Current pharmacologic strategies for the treatment of obesity remain ineffective at achieving long-term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules and biologics capable of regulating systemic nutrient homeostasis. Mitochondria present a unique opportunity for drug targeting by regulating systemic nutrient flux across tissues and cell types. However, unfavorable pharmacokinetic properties, off-target effects, and poor tolerability have limited clinical application. Herein, we evaluated the effects of BAM15 on body weight regulation and skeletal muscle mitochondrial function. 16 (n=8 per group) diet induced obese (DIO) male C57BL/6J mice were randomized to 3 weeks of high fat diet (HFD) or BAM15 (HFD + 0.01% w/w BAM15). After 3 weeks, mixed gastrocnemius muscle was harvested after euthanasia and assessed for oxidative phosphorylation (OXPHOS) and electron transport (ETC) capacity [1], as well as [1-14C]palmitate oxidation ]2], as described previously. Mice treated chronically with BAM15 were resistance to dietary weight gain, attributable to reductions in fat accrual. BAM15 treated animals displayed increased skeletal muscle fatty acid oxidation. However, OXPHOS and ETC capacity with glucose or fatty acid substrates remained unchanged between control and BAM15 treated animals. We conclude that BAM15 is tolerable and efficacious small molecule for the treatment of obesity. Importantly, chronic administration of BAM15 does not result in mitochondrial fatigue or dysfunction, warranting further investigation into pre-clinical efficacy and tolerability.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: US LA Baton Rouge Noland RC, US OH Cleveland Hoppel CL

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Skeletal muscle 

Coupling state: OXPHOS, ET  Pathway:HRR: Oxygraph-2k 


Axelrod CL(1), Davuluri G(1), Zunica ERM(1), Noland RC(2), Hoppel CL(1,3), Kirwan JP(1)
  1. Integrated Physiology Molecular Medicine Lab
  2. Skeletal Muscle Physiology Lab; Pennington Biomedical Research Center, Baton Rouge, LA, USA
  3. Dept Pharmacology, Case Western Reserve Univ, Cleveland, OH, USA


  1. Ye F, Hoppel CL (2013) Measuring oxidative phosphorylation in human skin fibroblasts. Anal Biochem 437:52-8.
  2. Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O, Bain J, Stevens R, Dyck JR, Newgard CB, Lopaschuk GD, Muoio DM (2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7:45-56.
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