TY - JOUR

T1 - Central control of energy balance by amylin and calcitonin receptor agonists and their potential for treatment of metabolic diseases

AU - Zakariassen, Hannah Louise

AU - John, Linu Mary

AU - Lutz, Thomas Alexander

PY - 2020

Y1 - 2020

N2 - The prevalence of obesity and associated comorbidities such as type 2 diabetes and cardiovascular disease is increasing globally. Body-weight loss reduces the risk of morbidity and mortality in obese individuals, and thus, pharmacotherapies that induce weight loss can be of great value in improving the health and well-being of people living with obesity. Treatment with amylin and calcitonin receptor agonists reduces food intake and induces weight loss in several animal models, and a number of companies have started clinical testing for peptide analogues in the treatment of obesity and/or type 2 diabetes. Studies predominantly performed in rodent models show that amylin and the dual amylin/calcitonin receptor agonist salmon calcitonin achieve their metabolic effects by engaging areas in the brain associated with regulating homeostatic energy balance. In particular, signalling via neuronal circuits in the caudal hindbrain and the hypothalamus is implicated in mediating effects on food intake and energy expenditure. We review the current literature investigating the interaction of amylin/calcitonin receptor agonists with neurocircuits that induce the observed metabolic effects. Moreover, the status of drug development of amylin and calcitonin receptor agonists for the treatment of metabolic diseases is summarized.

AB - The prevalence of obesity and associated comorbidities such as type 2 diabetes and cardiovascular disease is increasing globally. Body-weight loss reduces the risk of morbidity and mortality in obese individuals, and thus, pharmacotherapies that induce weight loss can be of great value in improving the health and well-being of people living with obesity. Treatment with amylin and calcitonin receptor agonists reduces food intake and induces weight loss in several animal models, and a number of companies have started clinical testing for peptide analogues in the treatment of obesity and/or type 2 diabetes. Studies predominantly performed in rodent models show that amylin and the dual amylin/calcitonin receptor agonist salmon calcitonin achieve their metabolic effects by engaging areas in the brain associated with regulating homeostatic energy balance. In particular, signalling via neuronal circuits in the caudal hindbrain and the hypothalamus is implicated in mediating effects on food intake and energy expenditure. We review the current literature investigating the interaction of amylin/calcitonin receptor agonists with neurocircuits that induce the observed metabolic effects. Moreover, the status of drug development of amylin and calcitonin receptor agonists for the treatment of metabolic diseases is summarized.

KW - amylin

KW - amylin receptor agonists

KW - calcitonin receptor agonists

KW - energy balance

KW - metabolic disease

KW - salmon calcitonin

U2 - 10.1111/bcpt.13427

DO - 10.1111/bcpt.13427

M3 - Review

C2 - 32363722

AN - SCOPUS:85084826679

VL - 127

SP - 163

EP - 177

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

SN - 1742-7835

IS - 3

ER -