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[PMID]: | 28109166 |
[Au] Autor: | Gydesen S; Hjuler ST; Freving Z; Andreassen KV; Sonne N; Hellgren LI; Karsdal MA; Henriksen K |
[Ad] Endereço: | Nordic Bioscience, Herlev, Denmark. |
[Ti] Título: | 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. |
[So] Source: | Br J Pharmacol;174(7):591-602, 2017 Apr. | [Is] ISSN: | 1476-5381 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: Rats fed a high-fat diet were treated, s.c., with KBP-089 0.625, 1.25, 2.5 µg·kg or vehicle. KB-089 induced in a dose-dependent and sustained weight loss (~17% by 2.5 µg·kg ). 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. CONCLUSIONS AND IMPLICATIONS: 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. |
[Mh] Termos MeSH primário: |
Tecido Adiposo/efeitos dos fármacos Adiposidade/efeitos dos fármacos Preferências Alimentares/efeitos dos fármacos Receptores da Calcitonina/agonistas Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas/metabolismo Perda de Peso/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Agonistas dos Receptores da Amilina/farmacologia Animais Dieta Hiperlipídica Relação Dose-Resposta a Droga Glucose/metabolismo Homeostase/efeitos dos fármacos Masculino Tamanho da Partícula Ratos Ratos Sprague-Dawley Ratos Zucker Relação Estrutura-Atividade
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Amylin Receptor Agonists); 0 (Receptors, Calcitonin); 0 (Receptors, Islet Amyloid Polypeptide); IY9XDZ35W2 (Glucose) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171106 |
[Lr] Data última revisão:
| 171106 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170122 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1111/bph.13723 |
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