A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference

Sofie Gydesen, Sara Toftegaard Hjuler, Zenia Freving, Kim Vietz Andreassen, Nina Sonne, Lars Hellgren, Morten Asser Karsdal, Kim Henriksen

Research output: Contribution to journalJournal articleResearchpeer-review

498 Downloads (Pure)

Abstract

Background and Purpose
Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges – hence, development of weight loss therapies with the ability to reduce the co-morbidities is key.

Experimental Approach
The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on bodyweight, glucose homeostasis, and fatty acid accumulation in liver and muscle tissue, food preference was investigated. Further, we elucidate weight-independent effects of KBP-089 using a weight-matched group.

Key Results
High fat diet fed rats were treated with KBP-089 s.c., at 0.625, 1.25, 2.5 µg∙kg-1 and vehicle resulting in a dose-dependent and sustained ~17% weight loss by the 2.5 µg∙kg-1 (p < 0.001). Moreover, KBP-089 reduced fat depot size and reduced lipid accumulation in muscle and liver.
In Zucker Diabetic Fatty rats, KBP-089 improved glucose homeostasis through improved insulin action.
To obtain a weight-matched group, significantly less food was offered (9% less than in the KBP-089 group). Weight-matching led to improved glucose homeostasis through lowered plasma insulin; however, these were inferior to the effect of KBP-089.
In the food preference test, normal diet rats obtained 74% of their calories from chocolate. KBP-089 administration reduced total caloric intake, and induced a relative increase in chow consumption while drastically lowering the chocolate compared to vehicle.

Conclusion
The novel DACRA, KBP-089 induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet-induced weight loss.
Original languageEnglish
JournalBritish Journal of Pharmacology
Volume174
Pages (from-to)591-602
ISSN0007-1188
DOIs
Publication statusPublished - 2017

Keywords

  • Amylin
  • DACRA
  • Obesity
  • Adiposity
  • Body composition
  • Insulin sensitivity

Fingerprint

Dive into the research topics of 'A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference'. Together they form a unique fingerprint.

Cite this