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Regulation of Hepatic Metabolism by the Mechanistic Target of Rapamycin

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Hepatic De Novo Lipogenesis and Regulation of Metabolism

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Abstract

Lipids are essential for many cellular and organismal processes, yet an excess of lipids can cause toxicity. The liver is a key organ for the maintenance of lipid homeostasis, performing lipogenesis as well as mediating the exchange of lipoproteins with peripheral tissues. In this chapter, we focus primarily on the regulation of lipogenesis in the liver by the protein kinase mTOR (mechanistic Target of Rapamycin), a central sensor of environmental cues that coordinates growth, protein synthesis and metabolism with nutrient availability. The mTOR protein kinase is found in two distinct complexes, each of which plays a role in the regulation of lipogenesis. We discuss the regulation of lipogenesis both directly by hepatic mTOR, indirectly by mTOR in other organs, and the regulation of hepatic lipogenesis by hormones and growth factors that regulate mTOR. This regulation by mTOR is an extremely complex process that we are only now beginning to fully understand.

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Acknowledgements

We would like to thank Emma Baar, Joseph Baur and Mathieu Laplante for their comments, all the members of the Lamming laboratory for their assistance and insight, and Dena Cohen for advice and consultation. We have previously explored some of the concepts and ideas in this chapter (Lamming and Sabatini 2013; Lamming 2014), and Figs. 3.2 and 3.3 are adapted from our recent publications on lipid metabolism and the regulation of the mTOR signaling pathway by the GH/IGF-1 axis (Lamming and Sabatini 2013; Lamming 2014). The Lamming lab is supported by a K99/R00 Pathway to Independence Award to D.W.L. from the National Institute of Health/National Institute on Aging (AG041765), as well as startup funds from the UW-Madison School of Medicine and Public Health and the UW-Madison Department of Medicine. This work was supported using facilities and resources at the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government.

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  1. Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison and William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, WSM VAH Room C3127 Research 151, Madison, WI, 53705, USA

    Dudley W. Lamming

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  1. Departments of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA

    James M. Ntambi

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Lamming, D.W. (2016). Regulation of Hepatic Metabolism by the Mechanistic Target of Rapamycin. In: Ntambi, J. (eds) Hepatic De Novo Lipogenesis and Regulation of Metabolism. Springer, Cham. https://doi.org/10.1007/978-3-319-25065-6_3

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