Compositions and methods for increasing energy metabolism

Inventors

Zemel, Michael • Bruckbauer, Antje • Baggett, Brooke

Assignees

Nusirt Sciences Inc

Abstract

Compositions and methods useful for inducing an increase in fatty acid oxidation or mitochondrial biogenesis, reducing weight gain, inducing weight loss, or increasing Sirt1, Sirt3, or AMPK activity are provided herein. Such compositions comprise a combination of a PDE 5 inhibitor, such as sildenafil or icariin, and resveratrol, and a branched amino acid such as leucine, or its metabolite.

Core Innovation

The disclosure describes compositions and methods to increase energy metabolism by administering a synergistic combination that includes a phosphodiesterase 5 (PDE 5) inhibitor and a branched-chain amino acid, notably leucine, or leucine metabolites. The leucine metabolites include keto-isocaproic acid (KIC), alpha-hydroxy-isocaproic acid, and beta-hydroxymethylbutyrate (HMB). The approach is directed to increasing energy metabolism features associated with fatty acid oxidation and mitochondrial biogenesis.

The described synergy is supported by in vitro observations in adipocytes and myotubes, where the combination increases fatty acid oxidation, glucose utilization, nitric oxide production, and mitochondrial biogenesis. The disclosure further ties these effects to energy metabolism regulators such as PGC1-α and mitochondrial biomass, and includes associations with Sirt1, Sirt3, and AMPK in the context of mitochondrial and metabolic responses.

The disclosure also describes in vivo improvements in a diet-induced obesity/insulin resistance mouse model using the synergistic combinations. Reported outcomes include reduced post-prandial and fasting glucose, improved insulin sensitivity and insulin tolerance, reduced liver mass, and reduced C-reactive protein (CRP). The composition concepts include administering leucine and/or leucine metabolites together with a synergistically effective amount of a PDE 5 inhibitor comprising sildenafil, with optional additional agents such as resveratrol, vitamin B6, and metformin.

Claims Coverage

The provided claim set includes one independent claim. The inventive features are centered on a synergistic composition administered for obesity treatment, combining specified leucine and leucine metabolites with a PDE 5 inhibitor comprising sildenafil.

Overall, the claim coverage focuses on a single independent claim requiring obesity treatment via co-administration of specified leucine and/or leucine metabolites with a synergistically effective amount of a PDE 5 inhibitor comprising sildenafil.

Stated Advantages

Documented Applications