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Commentary Free access | 10.1172/JCI130755

Antiobesogenic effects of central GIPR antagonism

Jessica T. Y. Yue1 and Tony K. T. Lam2,3,4,5

1Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.

2Toronto General Hospital Research Institute, University Health Network (UHN), Toronto, Ontario, Canada.

3Department of Physiology,

4Department of Medicine, and

5Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.

Address correspondence to: Jessica Yue, 7-21 Medical Sciences Building, Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G2H7. Phone: 780.248.5804; Email: jessica.yue@ualberta.ca. Or to: Tony Lam, MaRS Centre, 101 College Street, Toronto Medical Discovery Tower, 10th floor, Room 705, Toronto, Ontario, Canada M5G1L7. Phone: 416.581.7880; Email: tony.lam@uhnres.utoronto.ca.

Find articles by Yue, J. in: JCI | PubMed | Google Scholar

1Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.

2Toronto General Hospital Research Institute, University Health Network (UHN), Toronto, Ontario, Canada.

3Department of Physiology,

4Department of Medicine, and

5Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.

Address correspondence to: Jessica Yue, 7-21 Medical Sciences Building, Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G2H7. Phone: 780.248.5804; Email: jessica.yue@ualberta.ca. Or to: Tony Lam, MaRS Centre, 101 College Street, Toronto Medical Discovery Tower, 10th floor, Room 705, Toronto, Ontario, Canada M5G1L7. Phone: 416.581.7880; Email: tony.lam@uhnres.utoronto.ca.

Find articles by Lam, T. in: JCI | PubMed | Google Scholar

Published August 12, 2019 - More info

Published in Volume 129, Issue 9 on September 3, 2019
J Clin Invest. 2019;129(9):3532–3535. https://doi.org/10.1172/JCI130755.
© 2019 American Society for Clinical Investigation
Published August 12, 2019 - Version history
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Abstract

Developing effective treatments for obesity and related metabolic disease remains a challenge. One logical strategy targets the appetite-regulating actions of gut hormones such as incretins. One of these incretins, glucose-dependent insulinotropic polypeptide (GIP), has garnered much attention as a potential target: however, whether it is beneficial to boost or block the action of GIP to promote weight loss remains an unresolved question. In this issue of the JCI, Kaneko and colleagues show that antagonizing GIP signaling in the CNS enhances the weight-reducing effects of leptin in rodents with diet-induced obesity. The authors posit that an increase in circulating intestinally derived GIP, as a consequence of overnutrition, acts in the brain to impair hypothalamic leptin action, resulting in increased food intake and body weight gain. This research advances the idea that multiple GIP signaling pathways and mechanisms exist in the obese state and offers intriguing insights into the antiobesogenic consequences of antagonizing brain GIP action.

Version history
  • Version 1 (August 12, 2019): Electronic publication
  • Version 2 (September 3, 2019): Print issue publication
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