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Diabetes. 2016 Feb;65(2):421-32. doi: 10.2337/db15-0889. Epub 2015 Nov 13.

Uroguanylin Action in the Brain Reduces Weight Gain in Obese Mice via Different Efferent Autonomic Pathways.

Author information

1
Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo, Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria, Santiago de Compostela, Travesía da Choupana s/n, Santiago de Compostela, Spain Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain CIBER Fisiopatología de la Obesidad y Nutrición, Spain.
2
Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain CIBER Fisiopatología de la Obesidad y Nutrición, Spain.
3
Laboratory of Metabolism, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
4
Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo, Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria, Santiago de Compostela, Travesía da Choupana s/n, Santiago de Compostela, Spain CIBER Fisiopatología de la Obesidad y Nutrición, Spain Department of Pediatrics, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
5
Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
6
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
7
CIBER Fisiopatología de la Obesidad y Nutrición, Spain Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.
8
Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo, Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigación Sanitaria, Santiago de Compostela, Travesía da Choupana s/n, Santiago de Compostela, Spain CIBER Fisiopatología de la Obesidad y Nutrición, Spain luisamaria.seoane@usc.es ruben.nogueiras@usc.es.
9
Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain CIBER Fisiopatología de la Obesidad y Nutrición, Spain luisamaria.seoane@usc.es ruben.nogueiras@usc.es.

Abstract

The gut-brain axis is of great importance in the control of energy homeostasis. The identification of uroguanylin (UGN), a peptide released in the intestines that is regulated by nutritional status and anorectic actions, as the endogenous ligand for the guanylyl cyclase 2C receptor has revealed a new system in the regulation of energy balance. We show that chronic central infusion of UGN reduces weight gain and adiposity in diet-induced obese mice. These effects were independent of food intake and involved specific efferent autonomic pathways. On one hand, brain UGN induces brown adipose tissue thermogenesis, as well as browning and lipid mobilization in white adipose tissue through stimulation of the sympathetic nervous system. On the other hand, brain UGN augments fecal output through the vagus nerve. These findings are of relevance as they suggest that the beneficial metabolic actions of UGN through the sympathetic nervous system do not involve nondesirable gastrointestinal adverse effects, such as diarrhea. The present work provides mechanistic insights into how UGN influences energy homeostasis and suggests that UGN action in the brain represents a feasible pharmacological target in the treatment of obesity.

PMID:
26566631
DOI:
10.2337/db15-0889
[Indexed for MEDLINE]
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