Scientific publications

Elucidating the Role of Peripheral Neurotensin in Appetite Control

Sep 15, 2021 | Magazine: Endocrinology

Maitane Izaguirre  1 , Victoria Catalán  1 , Gema Frühbeck  1

The obesity epidemic compels researchers and the pharmaceutical industry to strive for new drugs. Although eagerly pursued for decades, obesity pharmacotherapy has thus far shown only limited success. Many new agents announced as the antiobesity solution were hurriedly withdrawn due to serious side-effects and health risks.

Therefore, new treatments for obesity that are both more effective and better tolerated are urgently needed. In this context, major recent advances in our understanding of the basic neurobiology of appetite and energy homeostasis have identified numerous targets for potential antiobesity drug development (1).

Noteworthy, our insight into the regulation of appetite and metabolism has improved considerably over the last decades stimulated, among others, by observations after bariatric surgery (2). In an elegant study, Ratner et al (3) in this issue add neurotensin (NT) to the key elements involved in the intricate energy homeostasis regulation circuitry. NT, a 13-amino acid peptide expressed in the brain as well as localized in specialized enteroendocrine cells of the small intestine, is released by fat ingestion and facilitates fatty acid translocation.

Although brain NT is known to inhibit food intake, the effects of peripheral NT have been less investigated. Ratner et al (3) show via both in vivo and ex vivo work that peripheral NT inhibits food intake (Figure 1), whereas circulating and gastrointestinal NTs are increased after gastric bypass surgery (Figure 2).

Accordingly, the authors conclude that peripheral NT should be included among the appetite-regulating gut hormones and that stable NT formulations, such as pegylated NT, which improve the pharmacokinetics of the peptide prolonging its half-life and thereby extending its anorexigenic effect, may be a useful antiobesity agent.

CITATION  Endocrinology. 2016 Sep;157(9):3391-3.  doi: 10.1210/en.2016-1542.