title: A novel dual amylin and calcitonin receptor agonist, KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference.
abstract: Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities.
  
  
  
  The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight-independent effects of KBP-089 using a weight-matched group.
  
  
  
  Rats fed a high-fat diet were treated, s.c., with KBP-089 0.625, 1.25, 2.5 μg·kg-1or vehicle. KB-089 induced in a dose-dependent and sustained weight loss (~17% by 2.5 μg·kg-1). 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 by reducing plasma insulin; however, these effect were inferior compared to those of KBP-089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP-089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle.
  
  
  
  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.
authors.affiliation: Nordic Bioscience, Herlev, Denmark.|Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Sofie
authors.initials: S
authors.lastname: Gydesen
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Sara Toftegaard
authors.initials: ST
authors.lastname: Hjuler
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Zenia
authors.initials: Z
authors.lastname: Freving
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Kim Vietz
authors.initials: KV
authors.lastname: Andreassen
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Sonne
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Hellgren
authors.affiliation: Nordic Bioscience, Herlev, Denmark.|KeyBioscience AG, Stans, Switzerland.
authors.forename: Morten Asser
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D050154:Adiposity / Q000187:drug effects*; D065091:Amylin Receptor Agonists / Q000494:pharmacology; D000818:Animals; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D005518:Food Preferences / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D018003:Receptors, Calcitonin / Q000819:agonists*; D058287:Receptors, Islet Amyloid Polypeptide / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D065091:Amylin Receptor Agonists; D018003:Receptors, Calcitonin; D058287:Receptors, Islet Amyloid Polypeptide; D005947:Glucose