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Review
. 2020 Apr 7;31(4):679-698.
doi: 10.1016/j.cmet.2020.02.014. Epub 2020 Mar 17.

Leveraging the Gut to Treat Metabolic Disease

Ruth E Gimeno  1 , Daniel A Briere  1 , Randy J Seeley  2
Affiliations
Review

Leveraging the Gut to Treat Metabolic Disease

Ruth E Gimeno et al. Cell Metab. .

Abstract

25 years ago, the future of treating obesity and diabetes focused on end organs known to be involved in energy balance and glucose regulation, including the brain, muscle, adipose tissue, and pancreas. Today, the most effective therapies are focused around the gut. This includes surgical options, such as vertical sleeve gastrectomy and Roux-en-Y gastric bypass, that can produce sustained weight loss and diabetes remission but also extends to pharmacological treatments that simulate or amplify various signals that come from the gut. The purpose of this Review is to discuss the wealth of approaches currently under development that seek to further leverage the gut as a source of novel therapeutic opportunities with the hope that we can achieve the effects of surgical interventions with less invasive and more scalable solutions.

Keywords: bariatric surgery; gastrointestinal tract; gut peptides; obesity; type 2 diabetes.

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Conflict of interest statement

Declaration of Interests Ruth Gimeno and Daniel Briere are both employees of Eli Lilly and Company. Randy Seeley has served as a paid consultant and/or advisory board member to Novo Nordisk, Scohia, Sanofi, Kintai Therapeutics, and Ionis. He has equity or option positions in Zafgen and ReDesign Health. He has received research support from Novo Nordisk, Zafgen, Pfizer, Kintai Therapeutics, and Ionis.

Figures

Figure 1:
Figure 1:
Traditionally, therapeutic approaches to obesity and type 2 diabetes have focused on altering the actions of key effector organs such as brain, liver, pancreas, adipose tissue and muscle. Surgical alterations of the GI tract by either RYGB or VSG result in sustained weight loss and potent improvements and even remission of type 2 diabetes. Targeting the GI tract for therapies, therefore, can leverage signals from the GI tract to regulate each of these effector organs.
Figure 2:
Figure 2:
Major gut hormones that regulate metabolic function Here, we highlight some major gut peptides in terms of site of secretion, site and effort organ of action, and functions with emphasis on molecules whose therapeutic potential have been explored in clinical studies.
See this image and copyright information in PMC

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