Elsevier

Physiology & Behavior

Volume 104, Issue 4, 26 September 2011, Pages 621-623
Physiology & Behavior

Gut fat sensing in the negative feedback control of energy balance — Recent advances

https://doi.org/10.1016/j.physbeh.2011.05.003Get rights and content

Abstract

Infusions of lipids into the small intestine potently suppress ongoing feeding. Prior work has identified potential roles for gut extrinsic vagal and non-vagal sensory innervation in mediating the ability of gut lipid infusions to reduce food intake, but the local biochemical processes underlying gut lipid sensing at the level of the small intestine remain unclear. This manuscript will summarize recent progress in the identification and characterization of several candidate gut lipid sensing molecules important in the negative feedback control of ingestion, including the fatty acid translocase CD36, peroxisome proliferator-activated receptor alpha (PPAR-α), and the fatty acid ethanolamide oleoylethanolamide (OEA). In addition, this manuscript addresses a larger role for gut lipid sensing in the overall control of energy availability by modulating not only food intake but also hepatic glucose production.

Highlights

► Small intestinal fat infusions suppress feeding via extrinsic gut sensory nerves. ► CD36, PPAR α , and oleoylethanolamide may mediate gut lipid sensing in feeding. ► Duodenal fat stimulates a gut -brain -liver circuit to affect glucose homeostasis.

Introduction

The infusion of lipid emulsions into the small intestine has been demonstrated to rapidly and potently suppress food intake in multiple mammalian species, including man [1]. A role for sensory gut innervation in this phenomenon was suggested by studies showing that local infusion of the anesthetic tetracaine blocked the ability of duodenal lipid infusions to suppress sham feeding, where ingested food drains from the stomach during a meal without impinging on the duodenum [2]. Subsequent work supported a role for luminal sensory innervation in transmitting gut lipid negative feedback signals, in that local luminal application of the neurotoxin capsaicin, which selectively affects a subpopulation of unmyelinated afferent fibers, blocked the ability of intestinal infusions the fatty acid sodium oleate to inhibit sham feeding [3]. Extrinsic afferent innervation of the gut from both vagal and non vagal sources has been implicated in the ability of duodenal lipid infusions to inhibit food intake in rodent models, as gut vagal deafferentation, as well as surgical transection of gut splanchnic nerves and removal of the celiac superior mesenteric ganglion, each blocked the ability of duodenal corn oil infusions to reduce food intake during a meal [4]. Intestinal lipid infusions at feeding inhibitory doses also stimulate c-fos expression, a marker of neuronal activation, in the caudal brainstem nucleus of the solitary tract (NTS), the central nervous system terminus of gut vagal afferents [5]. Vagal capsaicin treatment blocks the ability of gut lipids to activate brainstem NTS c-fos, further supporting a role for gut vagal afferents in determining the feeding inhibitory effects of duodenal fat infusions. Furthermore, vagal afferents supplying the jejunum have been reported to be directly activated by local infusion of lipids and fatty acids [24]. Taken together, these data suggest that the proximal gut senses lipids, and communicates information regarding gut lipid availability to the central nervous system sites important in the control of feeding behavior via extrinsic gut sensory nerves.

Recent advances in understanding the molecular and systems biology of the gut–brain axis have suggested novel candidate gut lipid sensors, and have revealed roles for lipid sensing in the control of nutrient availability by modulating hepatic glucose production. These advances are outlined below.

Section snippets

Molecular mediators of gut lipid sensing

While the precise biochemical bases for gut lipid sensing remain elusive, several studies have begun to identify locally released or expressed factors potentially important in the gut–brain feedback control of ingestion. One target is duodenal serotonin (5-HT) release acting via vagal serotonin 3 (5-HT3) ionotropic receptors. The ability of intestinal lipid infusions to inhibit food intake and activate brainstem NTS c-fos is blocked by administration of the selective 5-HT3 receptor antagonist

Gut lipid sensing in the control of glucose homeostasis

In terms of the neurobiological controls of feeding, gut lipid detection has largely been construed as a sensory capability important in generating neuroendocrine negative feedback signals that limit food intake. From physiological and behavioral perspectives, the delivery of energy dense lipid into the gastrointestinal tract functions in part to limit further nutrient availability by terminating an ongoing meal. More broadly, new studies suggest that gut lipid sensing may play a significant

Acknowledgements

This work was supported by NIH DK066618, DK020541 and the Skirball Institute for Nutrient Sensing.

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