Elsevier

Physiology & Behavior

Volume 105, Issue 1, 30 November 2011, Pages 27-35
Physiology & Behavior

Oral fatty acid signaling and intestinal lipid processing: Support and supposition

https://doi.org/10.1016/j.physbeh.2011.02.016Get rights and content

Abstract

There is increasing recognition that specialized processes once thought to be relatively isolated to the oral cavity (e.g., taste) and intestine (e.g., nutrient absorption) are better characterized as common and continuous. This is exemplified by accumulating evidence linking oral detection of dietary fats to their intestinal processing. This review first summarizes this literature focusing on purported gustatory signaling by free fatty acid stimulation and enterocyte lipid storage and mobilization in humans. It then willfully speculates on the possible functions of this integrated system. It is proposed that it may aid absorption of fat soluble nutrients, enhance acute energy intake, sustain intestinal function during long inter-meal intervals, modulate appetite and/or detoxify ingested compounds including free fatty acids.

Highlights

► Free fatty acids are effective signaling molecules in the oral cavity of humans though there is marked inter-individual variability in sensitivity. They are ligands for an array of putative fat receptors on taste receptor cells, but may also activate olfactory and trigeminal neurons. ► Oral fat detection influences lipid metabolism. It promotes a rapid rise in serum triacylglycerol, possibly by mobilizing lipid stored in the enterocyte from the previous eating event as well as by reducing the clearance rate through reduced adipocyte lipoprotein lipase activity. ► Oral (taste) detection thresholds for free fatty acids are not related to BMI, but there is a positive association between BMI and the post-stimulation serum triacylglycerol concentration for full-fat stimuli. This is less robust for fat-free versions of the same food. ► The functions of oral fat detection are poorly characterized, but may include, modulation of lipid trafficking in the enterocyte, detoxification of lipophilic cytotoxic compounds, appetite, energy intake and/or fat soluble nutrient absorption.

Section snippets

Gustatory detection of FFA

Dietary fats are clearly detected when in the oral cavity by tactile [30] and retronasal olfactory cues [31]. If there is a gustatory component as well, FFA are the most likely effective stimuli. There is no known or proposed receptor for triglyceride, the predominant form of lipid in the diet, as its ligand. A number of rodent studies indicate that esterified fatty acids are not effective stimuli [32], [33], [34], [35], [36]. Psychophysical studies indicate that humans can detect FFA with

Fatty acid signaling

Fatty acids are critical components of cell signaling processes through multiple mechanisms [7]. As integral components of cellular lipid membranes, they modulate cellular uptake of signaling compounds by diffusion and through channels. Additionally, the nature of fatty acids in lipid rafts determines the efficacy for docking of signaling proteins [6], [7]. Fatty acids are also precursors for hormones and substrates in signaling pathways [45]. Further, they are modulators of intracellular

Oral fat detection and lipid processing

Oral detection of dietary fats and fatty acids may be assessed by psychophysical methods, as noted above, or through measurement of biomarkers of lipid metabolism, most commonly, a change of serum triacylglycerol concentration [14], [15], [16], [18], [19], [20], [21], [22], [23], [24], [25]. It is hypothesized that oral exposure to fat leads to afferent signals carried by gustatory nerves to the nucleus of the solitary tract followed by reflexive efferent vagus activity that alters intestinal

Lipid storage in and mobilization from the GI tract

A number of studies indicate that ingestion of a high-fat meal leads to a greater post-prandial TAG concentration after ingestion of the subsequent meal; i.e., second-meal effect [15], [16], [64], [65], [66]. Increased release of pre-formed chylomicrons stored in the lamina propria, lacteals and/or lymph [15], [55], [67], [68] and increased hepatic VLDL production and secretion may be contributors [18]. However, contrary to popular views, accumulating evidence indicates that a substantive

Oral fat detection and post-prandial serum TAG concentrations

Multiple trials from different laboratories have demonstrated that oral stimulation alters post-prandial lipid concentrations [14], [15], [16], [18], [19], [20], [21], [22], [23], [24], [25], [55], [56]. An early study designed to examine the kinetics of vitamin A absorption noted that food intake after vitamin loading led to a rapid rise of plasma vitamin A concentrations [55] reflecting a rise of TAG since the vitamin is fat soluble. A follow-up controlled, modified-sham feeding trial (using

Post-prandial TAG concentration and risk for cardiovascular disease

Earlier assessments of the association between TAG concentrations and cardiovascular disease (CVD) focused on resting values, in large part, because they were viewed as less variable and more representative of lipid metabolism. Univariate analyses often revealed a positive association, but this was diminished in multivariate assessments. However, recognition that with increased eating frequency, people are effectively in a postprandial state much of the day, attention turned to the predictive

Functions of oral fat detection

One of the more perplexing questions related to the findings of enterocyte lipid storage and sensory mobilization of the pool concerns the function of this relationship. Evidence that elevated TAG is a risk factor for CVD suggests that the association poses a health risk, but this may only hold in the present environment. Beneficial roles would be predicted for the evolution and maintenance of such an integrated system. The following discussion speculates on possible functions with the intent

Intake

The first issue to address concerns the role of oral fat detection on fat ingestion as dietary fat is the likely primary source of lipid for the intestinal pool. Fat in foods may be detected by all human sensory systems, but each can lead to a different affective response. Fat is consumed in high quantity by many populations, in part, because it contributes a palatable sensory sensation. This is primarily attributable to its tactile properties (e.g., viscosity and lubricity) and delivery of

Fat soluble nutrient absorption

Vitamin A is a fat-soluble compound and is often used in clinical trials as a marker for lipid absorption. Effects of sensory stimulation on vitamin A absorption were described half a century ago through a series of studies prompted by a serendipitous observation [55]. Vitamin A palmitate mixed with corn oil was administered to 16 healthy individuals with normal vitamin A status, but five participants exhibited little absorption over the following 8 h period. During a trial, one of these

Facilitation of feeding via impaired leptin signaling

Leptin's role in appetite and feeding regulation has not been fully described. Most commonly, it is regarded as a satiety hormone that reduces eating frequency [80]. However, it is relatively ineffective in obese individuals, possibly due to limited transport across the blood brain barrier and access to its target sites [81]. This could be attributable to elevated circulating TAG which is common in the obese and inhibits such transport [82]. Alternatively, it may be that leptin functions more

Intestinal energy pool

The GI tracts of vertebrates adapt to wide variations of ingestive behavior [86]. Generally, it is an organ with high energy demands due to the rapid turnover of its cells, support of various transport systems and synthetic processes. In humans, it extracts over 25% of arterial oxygen while constituting only 5% of body weight [87]. Because of the high cost of its maintenance, down-regulation of its activity and mass between eating events could offer an adaptive advantage. This has been clearly

Appetite regulation

Although strong evidence indicates that total energy flux is the principal determinant of body weight, individual macronutrients make unique contributions [94]. Within the GI tract, fats are involved as signaling molecules and substrates. Starting in the oral cavity, isolated taste cells can act as endocrine cells and secrete an array of “satiety” hormones (e.g., GLP-1, glucagon, and PYY) following topical application of glucose [95]. Further, GLP-1 concentrations increase with glucose

Detoxification

The FFA that serve multiple vital functions in the body are also cytotoxic if not appropriately packaged and stored [117]. This is most apparent in tissues with limited fat storage capacity under conditions of high fat intake. Lipotoxicity manifests as insulin resistance in skeletal muscle, abnormalities of pancreatic insulin secretion and apoptosis in multiple organs, including the heart. Enterocytes are exposed to the greatest fluxes of fat and so are at particular risk for lipotoxicity and

Summary

Enterocytes are exposed to wide fluxes of lipids and must dampen these oscillations within themselves and for other tissues in the body, so that none is exposed to either too much or too little of a good (e.g., essential fatty acid) or bad (e.g., free fatty acid) thing. It is posited that this function is aided by an upstream signaling system, taste, that increasingly appears to be capable of detecting fatty acids of varying properties and relaying this information down the GI tract to

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