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Glucagon and lipid signaling in the hypothalamus

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Abstract

Hyperglycemia, caused in part by elevated hepatic glucose production (GP), is a hallmark feature of diabetes and obesity. The hypothalamus responds to hormones and nutrients to regulate hepatic GP and glucose homeostasis. This invited perspective focuses on the molecular signaling and biochemical pathways involved in the gluco-regulatory action of hypothalamic glucagon signaling and lipid sensing in health and disease. Recent evidence generated via genetic, molecular and chemical experimental approaches indicates that glucagon and lipid signaling independently trigger complementary hypothalamic mechanisms to lower GP. Thus, targeting hypothalamic glucagon or lipid signaling may have therapeutic potential in diabetes and obesity.

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Acknowledgments

The work discussed in this review produced by the Lam laboratory was supported by research grants from the Canadian Diabetes Association (OG-3–13-4156-TL) and the Canadian Institute of Health Research (MOP-86554). Mary P. LaPierre is supported by an Ontario Graduate Scholarship and a UHN Unilever Graduate Fellowship in Neuroscience. Mona A. Abraham is supported by a Banting and Best Diabetes Center graduate scholarship. Jessica T. Y. Yue is supported by post-doctoral fellowships from the Canadian Institutes of Health Research and Canadian Diabetes Association. Tony K. T. Lam holds the J. K. McIvor (1915–1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity at the Toronto General Research Institute and the University of Toronto.

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Authors and Affiliations

  1. Toronto General Research Institute & Department of Medicine, University Health Network, Toronto, M5G 1L7, Canada

    Mary P. LaPierre, Mona A. Abraham, Beatrice M. Filippi, Jessica T. Y. Yue & Tony K. T. Lam

  2. Departments of Physiology, University of Toronto, Toronto, M5S 1A8, Canada

    Mary P. LaPierre, Mona A. Abraham & Tony K. T. Lam

  3. Departments of Medicine, University of Toronto, Toronto, M5S 1A8, Canada

    Tony K. T. Lam

  4. Banting and Best Diabetes Centre, University of Toronto, Toronto, M5G 2C4, Canada

    Tony K. T. Lam

  5. MaRS Centre, 101 College Street, Toronto Medical Discovery Tower, 10th floor, Room 705, Toronto, ON, M5G 1L7, Canada

    Tony K. T. Lam

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  1. Mary P. LaPierre
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  2. Mona A. Abraham
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  3. Beatrice M. Filippi
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  4. Jessica T. Y. Yue
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  5. Tony K. T. Lam
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Correspondence to Tony K. T. Lam.

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Mary P. LaPierre and Mona A. Abraham have contributed equally to this invited perspective.

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LaPierre, M.P., Abraham, M.A., Filippi, B.M. et al. Glucagon and lipid signaling in the hypothalamus. Mamm Genome 25, 434–441 (2014). https://doi.org/10.1007/s00335-014-9510-6

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