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Signalling from the periphery to the brain that regulates energy homeostasis

Abstract

The CNS regulates body weight; however, we still lack a clear understanding of what drives decisions about when, how much and what to eat. A vast array of peripheral signals provides information to the CNS regarding fluctuations in energy status. The CNS then integrates this information to influence acute feeding behaviour and long-term energy homeostasis. Previous paradigms have delegated the control of long-term energy homeostasis to the hypothalamus and short-term changes in feeding behaviour to the hindbrain. However, recent studies have identified target hindbrain neurocircuitry that integrates the orchestration of individual bouts of ingestion with the long-term regulation of energy balance.

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Figure 1: Peripheral-to-CNS signals of energy status.
Figure 2: Endocrine and neuronal pathways to the CNS.
Figure 3: Roux-en Y gastric bypass and vertical sleeve gastrectomy.
Figure 4: The impact of bariatric surgery on intestinal signalling peptides.

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Acknowledgements

The authors' work is supported in part by US National Institutes of Health awards DK082480 (D.A.S.) and DK093848 (R.J.S.).

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D.A.S. researched data for the article, made a substantial contribution to the discussion of content and contributed to the writing, review and editing of the manuscript before submission. K.-S.K. researched data for the article, made a substantial contribution to the discussion of content and contributed to the writing of the manuscript. R.J.S. reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Darleen A. Sandoval.

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Competing interests

K.-S.K. has no competing interest. R.J.S. has received research support from Ethicon Endo-Surgery, Novo Nordisk, Sanofi and Janssen. R.J.S. has served on scientific advisory boards for Ethicon Endo-Surgery, Daiichi Sankyo, Janssen, Novartis, Nestle, Takeda, Boehringer Ingelheim, Sanofi and Novo Nordisk. R.J.S. is also a paid speaker for Ethicon Endo-Surgery. D.A.S. has received research support from Ethicon Endo-Surgery, Novo Nordisk and Boehringer Ingelheim.

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Glossary

Vagus nerve

The longest cranial nerve. It contains both motor and sensory fibres involved in the parasympathetic regulation of homeostatic processes.

Enteroendocrine cells

Specialized endocrine cells within the intestine that secrete peptides important for regulating feeding and metabolism.

Afferent neurons

Peripheral sensory neurons that carry ascending nerve impulses from peripheral organs to the brain and spinal cord.

G-Protein-coupled receptor

(GPCR). Seven-transmembrane receptor that is coupled to, and activates, a heterotrimeric G protein, which subsequently activates a series of downstream signalling cascades; this receptor class is large and diverse and binds to a variety of nutrients and hormones.

Nodose ganglion

Contains the cell bodies of neurons of the vagus nerve.

Nutrient sensing

A process by which nutrients or their by-products directly activate cell signalling cascades that, in turn, regulate metabolism.

Efferent neurons

Peripheral motor neurons that carry descending nerve impulses from the CNS to peripheral organs.

Bariatric surgery

A surgical dissection and/or reorganization of the gastrointestinal tract that is used to induce weight loss.

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Kim, KS., Seeley, R. & Sandoval, D. Signalling from the periphery to the brain that regulates energy homeostasis. Nat Rev Neurosci 19, 185–196 (2018). https://doi.org/10.1038/nrn.2018.8

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