Regulation of food intake is a complex system that involves numerous physiological signals or hormones from the gastrointestinal tract and the brain. The hypothalamus and brainstem are principal targets of gastrointestinal signals—either directly or via the vagus nerve. Examples of these signals include peptide YY3-36, oxyntomodulin, glucagon-like peptide-1, and cholesystokinin (Chaudhri et al., 2008). Within the hypothalamus, these signals inhibit or increase food intake. Communication between the brainstem and hypothalamus and the vagus nerve modulates food intake and even body weight through a constellation of signals and their respective transporters and receptors (Roggee et al., 2008).
Excessive weight gain reflects a disequilibrium of energy expenditure and energy intake (Hofbauer et al., 2007). The interplay of genetics and epigenetics that, in part, influence hunger and satiety processes and the adipose-gut-brain relationships that tend to favor weight gain have contributed to the development of several models to explain this phenomenon (Mietus-Snyder and Lusting, 2008; Schwartz and Niswender, 2004). Whether it is preservation of the species, bio-chemical signaling thresholds, and/or defects (e.g., leptin and insulin dynamics), a common pathological disruption of hormone signaling remains elusive.
Five decades of research with ethanolamindes, a family of naturally occurring lipids, now suggests oleolyethanolmide (OEA), a lipid derived from phosphotidylcholine (lecithin) in the cell membrane lipid bi-layer, plays a role in signaling satiety (Lo Verme et al., 2005). Rodent models suggest that an OEA increase following a meal in a dose- and time-dependent manner contributes to decreased food intake. A hypothetical model implies that OEA accumulation, through several steps and activated receptors, ultimately communicates with the vagus nerve, thereby inducing satiety, at least in rodents. The oral and intra-peritoneal administration of OEA reduced meal frequency and increased inter-meal intervals, yet it appears that meal volume may not be impacted (Gaetani et al., 2003). Interestingly, OEA may be another factor that modulates hepatic lipogenesis and influences body weight (Fu et al., 2005).
During the deactivation of OEA in mammalian tissues, including the small intestine, oleic acid and ethanolamine are produced (Fu et al., 2007). Upon OEA deactivation or reduction, food consumption resumes, feeding frequency increases, and inter-meal intervals decrease.
Questions on the role of dietary oleic acid on satiety are of particular interest in the efforts to curb obesity, regulate food intake, and initiate meal satiety (Schwartz et al., 2008). Oleic acid (18:1, n-9) is the dominant fatty acid in olive oil (50–80%), high oleic acid soybean oil (~80%), and açai fruit pulp (~50%), and a significant component of grape seed oil (15–20%). The typical young adult (< 30 years of age) in the United States consumes nearly 13% of energy from monoenes, 93% of which is from oleic acid (Nicklas et al., 2004).
Intra-gastric perfusion studies with oleic acid among rodents indicated the presence of specific OEA transport (CD36) in the small intestine (duodenum, jejunum) mucosal cells that affect oleic acid uptake and influence enzyme activities involved in the synthesis and degradation of OEA. It is important to remember that many bioactive lipids, such as the endocannabinoids neurotransmitters anandamide and 2-arachidonolyglycerol, are derived from dietary n-6 fatty acids, which in this case is arachidonic acid (20:4, n-6). These and related compounds appear to have signaling functions involved in appetite, energy metabolism, pain perception, memory, and learning (Hansen and Artmann, 2008).
Similarly, oleic acid, when fed at pharmacological doses, may influence levels of OEA, a non-endocannabinoid acylethanolamide. Can dietary levels of oleic acid, a monoene, affect the tissue levels of OEA and ultimately impact the dysregulation of energy homeostasis and contribute to reduced body weight in humans? Evidence indicates modulation of eicosanoids and endocannabinoids may be influenced by dietary fat in short-term studies among rodents and piglets (Osei-Hyiaman et al., 2005; Berger et al., 2001).
There is one striking exception in human beings vs experimental systems. Based on our impulsive or emotional decisions, we have the capacity to override in an instant any of the regulatory mechanisms.
References for the above studies are available from the authors.
by Roger Clemens, Dr.P.H.,
Scientific Advisor, ETHorn, La Mirada, Calif.
by Peter Pressman, M.D.,
LCDR, Medical Corps, U.S. Navy