Neuropeptide Y in the noradrenergic neurones induces obesity and inhibits sympathetic tone in mice.

L H Vähätalo, S T Ruohonen, S Mäkelä, M Kovalainen, A Huotari, K A Mäkelä, J A Määttä, I Miinalainen, R Gilsbach, L Hein, L Ailanen, M Mattila, K Eerola, M Röyttä, S Ruohonen, K-H Herzig, E Savontaus

Index: Acta Physiol. (Oxf.) 213(4) , 902-19, (2015)

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Abstract

Neuropeptide Y (NPY) co-localized with noradrenaline in central and sympathetic nervous systems seems to play a role in the control of energy metabolism. In this study, the aim was to elucidate the effects and pathophysiological mechanisms of increased NPY in catecholaminergic neurones on accumulation of body adiposity.Transgenic mice overexpressing NPY under the dopamine-beta-hydroxylase promoter (OE-NPY(DβH) ) and wild-type control mice were followed for body weight gain and body fat content. Food intake, energy expenditure, physical activity, body temperature, serum lipid content and markers of glucose homoeostasis were monitored. Thermogenic and lipolytic responses in adipose tissues, and urine catecholamine and tissue catecholamine synthesizing enzyme levels were analysed as indices of sympathetic tone.Homozygous OE-NPY(DβH) mice showed significant obesity accompanied with impaired glucose tolerance and insulin resistance. Increased adiposity was explained by neither increased food intake or fat absorption nor by decreased total energy expenditure or physical activity. Adipocyte hypertrophy and decreased circulating lipid levels suggested decreased lipolysis and increased lipid uptake. Brown adipose tissue thermogenic capacity was decreased and brown adipocytes filled with lipids. Enhanced response to adrenergic stimuli, downregulation of catecholamine synthesizing enzyme expressions in the brainstem and lower adrenaline excretion supported the notion of low basal catecholaminergic activity.Increased NPY in catecholaminergic neurones induces obesity that seems to be a result of preferential fat storage. These results support the role of NPY as a direct effector in peripheral tissues and an inhibitor of sympathetic activity in the pathogenesis of obesity.© 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.