High-fat feeding impairs nutrient sensing and gut brain integration in the caudomedial nucleus of the solitary tract in mice

PloS One
Althea R CavanaughClémence Blouet

Abstract

Hyperphagic obesity is characterized in part by a specific increase in meal size that contributes to increased daily energy intake, but the mechanisms underlying impaired activity of meal size regulatory circuits, particularly those converging at the caudomedial nucleus of the solitary tract in the hindbrain (cmNTS), remain poorly understood. In this paper, we assessed the consequences of high-fat (HF) feeding and diet-induced obesity (DIO) on cmNTS nutrient sensing and metabolic integration in the control of meal size. Mice maintained on a standard chow diet, low-fat (LF) diet or HF diet for 2 weeks or 6 months were implanted with a bilateral brain cannula targeting the cmNTS. Feeding behavior was assessed using behavioral chambers and meal-pattern analysis following cmNTS L-leucine injections alone or together with ip CCK. Molecular mechanisms implicated in the feeding responses were assessed using western blot, immunofluorescence and pharmacological inhibition of the amino acid sensing mTORC1 pathway (mammalian target of rapamycin complex 1). We found that HF feeding blunts the anorectic consequences of cmNTS L-leucine administration. Increased baseline activity of the L-leucine sensor P70 S6 kinase 1 and impaired L-leucine-...Continue Reading

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Citations

Feb 23, 2018·Journal of Molecular Endocrinology·José Luis SoengasMaría Jesús Delgado
Oct 20, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sara ComesañaJosé L Soengas
Jun 6, 2018·Frontiers in Physiology·John K Smith
Dec 10, 2016·Frontiers in Endocrinology·Nicholas Heeley, Clemence Blouet
Feb 19, 2021·Frontiers in Neuroscience·Laurent Gautron
Feb 26, 2021·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Tiffany N BuckleyJulie S Pendergast

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Software Mentioned

cmNTS
GraphPad Prism

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