"Weighing in" on synergy: preclinical research on neurohormonal anti-obesity combinations.
Active weight loss and the maintenance of a weight-reduced state elicit potent counter-regulatory responses in multiple neurochemical pathways rendering monotherapy-based anti-obesity agents relatively ineffective. Herein, we highlight potential strategies for overcoming counter-regulatory responses to states of negative energy balance using combinatorial approaches. We discuss methodological and practical considerations for preclinical modeling of additive/synergistic weight loss combinations that have emerged in our translational research program aimed at identifying naturally occurring neurohormonal synergies. As an example of synergy, pharmacological and mechanistic findings with the combined administration of the beta-cell hormone amylin and the adipokine leptin are reviewed. Finally, we briefly discuss what the future landscape of neurohormonal anti-obesity combinations may hold.
Roth
Jonathan D
JD
Amylin Pharmaceuticals, Inc., San Diego, CA 92121, USA. jonathan.roth@amylin.com
Trevaskis
James L
JL
Turek
Victoria F
VF
Parkes
David G
DG
D019440:Anti-Obesity Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism / Q000627:therapeutic use*; D020738:Leptin / Q000378:metabolism / Q000627:therapeutic use*; D009765:Obesity / Q000378:metabolism / Q000628:therapy*; D015431:Weight Loss / Q000502:physiology*
D019440:Anti-Obesity Agents; D058228:Islet Amyloid Polypeptide; D020738:Leptin