ARTICLE
Auteur(s) : Chryssanthi L Stylianopoulos1, Hiskias G
Keizer1,2
1Lipid Nutrition, BV, Nutrition & Toxicology
Department
2Lipid Nutrition, BV, Hogeweg 1, P.O. Box 4. 1520AA
Wormerveer, The Netherlands
Estimations of energy balance suggest that an increase in daily
caloric intake of 50 kcal more than energy expenditure can result
in a yearly increase in body weight of 1 to 2 kilos, contributing
to the development of obesity [1]. One potential strategy in the
fight against obesity is to reduce food intake by inducing satiety
and thus suppressing appetite.
Food intake induces a complex feedback system regulating hunger
and satiety. Intake, digestion and absorption of food are all
regulated by the nervous and the hormonal system [2].
Cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1) are two
key hormones in this system, which play an important role in
appetite regulation and are seen as major biomarkers for satiety
[3].
CCK release suppresses appetite and high concentrations of CCK
produce larger appetite-suppressing effects [4]. CCK can be induced
by fatty acids with a chain length of twelve carbons or longer [5,
6]. Long chain poly-unsaturated fatty acids (PUFA) have been shown
to produce a large increase in CCK response [6-12]. After ingestion
of long chain PUFA, free fatty acids (FFA) are hydrolyzed in the
gut lumen and CCK is secreted [13]. The effect of CCK release is
associated with a reduction in gastric motility and increase in
gastric distension, resulting in feelings of fullness and
inhibition of food intake [4]. TG hydrolysis is necessary for
induction of CCK release, and inhibition of lipase action has been
shown to markedly decrease CCK secretion [8, 13, 14].
Numerous studies have shown that exogenous CCK infusions reduce
food intake and suppress appetite [11, 15-20]. CCK antagonists
generally have the reverse effect on appetite and have been
associated with weight gain in rodents [21, 22].
GLP-1 is also known to be a potent regulator of food intake. It
has been shown that peripheral administration of GLP-1 reduces
energy intake in a dose-dependent manner in both lean and
overweight human subjects [23]. Much like CCK, GLP-1 is produced in
response to the presence of fat in the gut lumen [24]. GLP-1
release leads to a delay in gastric emptying, early satiety and a
decrease in food consumption, which serves as a negative feedback
signal to limit the amount of food consumed [14, 23-26].
Korean pine nut oil consists mainly of long chain
polyunsaturated fatty acids (PUFA) and has a uniquely high
concentration of pinolenic acid. The fatty acid profile of Korean
pine nut oil suggests a possible role on satiety hormone release.
This role is in line with the available evidence showing an
induction of satiety hormones and a consequent reduction of
appetite after ingestion of long-chain PUFA [7, 13, 27].
This report summarizes data from previously published studies to
support the role of Korean pine nut oil or PinnoThinTM
on satiety. First, in vitro data are presented to demonstrate the
stimulatory effect of PinnoThinTM on satiety hormones.
Second, data from two human randomized double-blind
placebo-controlled crossover trials are presented to show the
effect of PinnoThinTM on satiety hormones in vivo,
appetite sensations and food intake.
Effects of PinnoThin™ FFA on CCK release in vitro
Murine endocrine STC-1 cells were utilized in this study to
investigate the capacity of Korean pine nut oil or
PinnoThinTM to induce CCK compared to another type of
pine nut (Italian pine nut) and common dietary fatty acids [28].
STC-1 cells secrete CCK in response to a number of stimuli and are
a useful took for examining the pathways involved in CCK secretion
[29]. As a result to this exposure, the increase in CCK release was
measured (figure
1). Capric acid and Italian stone pine nut FFA produced
only a small amount of CCK release (46 pg/mL and 62 pg/mL
respectively). Different dietary fatty acids, namely oleic,
linoleic, and alpha-linolenic, produced an intermediate CCK release
(145 pg/mL, 138 pg/mL and 124 pg/mL respectively).
Korean pine nut oil FFA produced by far the largest CCK release
(493 pg/mL). The strong stimulating effect of Korean pine nut
FFA in vitro prompted further investigation. It was of great
interest to confirm the induction of CCK release by PinnoThin™ in a
human trial.
Effects of PinnoThin™ FFA and TG on gut satiety hormones and
appetite sensations
The effect of pine nut oil on CCK in humans was evaluated in a
randomized, double blind, placebo-controlled, cross-over trial
[28]. In this study, eighteen overweight, but otherwise healthy,
post-menopausal women participated in this study. They were given a
simple breakfast, consisting of two slices of white bread and
marmalade, along with 3G PinnoThin™ FFA, 3G PinnoThin™ TG or 3G
placebo (olive oil). Both CCK and GLP-1 release in the blood was
measured 30, 60, 90, 120, 180 and 240 minutes after the start of
the breakfast. During the same time period, subjective measures of
appetite sensations were quantified using a 100 mm visual
analogue scale (VAS). Each volunteer completed all three
interventions (PinnoThin™ FFA, PinnoThin™ TG and placebo) with 1
week wash-out in-between.
CCK release was significantly higher after PinnoThin™ TG and FFA
intake compared to placebo and (figure 2; p < 0.05). The
effect on CCK release became apparent after 60 minutes for the
PinnoThin™ TG and after 30 minutes for the PinnoThin™ FFA. The
total CCK release for PinnoThin™ TG was 22% higher compared to
placebo and 60% higher for PinnoThin™ FFA (p < 0.05). GLP-1
release was significantly higher after PinnoThin™ FFA compared to
placebo at 60 minutes (p < 0.05) (figure 3). The total GLP-1
release for PinnoThin™ FFA was 25% higher than placebo (p <
0.05).
When volunteers rated their prospective food consumption, which
is a measure of how much food the volunteers believed they could
consume, an effect of PinnoThin™ was observed. Prospective food
consumption, calculated by VAS scores, tended to be lower after
PinnoThin™ TG consumption (p = 0.06) and was significantly lower 30
minutes after PinnoThin™ FFA intake (p < 0.05).
In conclusion, this clinical trial showed that PinnoThin™
consumption is associated with increased release of the gut satiety
hormones CCK and GLP-1 and may influence feelings of satiety by
reducing prospective food intake.
Effects of PinnoThin™ FFA and TG on food intake, feeding
behaviour and appetite
The effect of PinnoThin™ TG and FFA was evaluated in a randomized
double-blinded placebo-controlled cross-over trial [30]. This trial
included 42 overweight, but otherwise healthy women. The volunteers
received a standard breakfast in the morning. Half an hour before
lunch time, they were given 2, 4, 6 g of PinnoThin™ TTG,
2 g of PinnoThin™ FFA or 2 g placebo (olive oil) in the
form of capsules with water. At lunch time, the volunteers received
an ad libitum buffet meal (containing high- and low-fat foods, both
sweet and savoury). The amount of food consumed was noted by the
difference in weight of the food plate pre- and post-lunch to the
nearest 0.1 g. In the evening, they received an ad libitum
supper, consisting of a pasta meal with ice cream dessert, which
was subsequently weighed. During the entire study day, subjective
measures of appetite and feeding behaviour were quantified using
VAS scores. Each volunteer completed all three interventions
(PinnoThin™ FFA, PinnoThin™ TG and placebo) with 1 week wash-out
in-between.
The study results found a statistically significant lower food
intake (9%) during lunch after PinnoThin™ FFA intake compared to
the placebo (p < 0.05). There was also a trend for reduction in
energy intake with PinnoThin™ FFA, 7% (p < 0.1). There was no
difference in food and energy intake between the groups for the
supper, indicating that the volunteers in the PinnoThin™ FFA group
did not overcompensate for the reduced lunch food and caloric
intake at supper. These differences found for PinnoThin™ FFA were
not observed for PinnoThin™ TG. No effects were seen on subjective
measures of appetite and feeding behaviour after PinnoThin™ FFA or
TG intake.
Previous studies have shown that PinnoThin™ TG is digested to
FFA, like similar dietary TG [31]. Furthermore, in the previous
PinnoThin™ trial [28], the effects of CCK response took longer to
develop for TG (60 minutes) compared to the FFA (30 minutes).
Consequently, insufficient time had passed between the intake of
the TG capsules and the ad libitum lunch for lipase action to
convert sufficient TG to FFA. Adequate TG hydrolysis is necessary
for induction of CCK release [8, 13, 14]. In addition, uptake of
fat from capsules could have been further delayed since there was
no simultaneous food ingestion [32]. Therefore, the differential
results seen in the case of PinnoThin™ FFA and TG are
anticipated.
In conclusion, this study showed that PinnoThin™ FFA directly
reduces food intake, without compensation during the subsequent
meal. The reduction in daily food intake observed with PinnoThin™
FFA, which corresponded to about 50 kcal, is biologically relevant.
This type of reduction on a daily basis could counteract a yearly
increase in body weight of 1 to 2 kg, which in the end leads
to overweight and obesity [1].
Conclusion
PinnoThin™ TG and FFA have been shown to increase satiety hormones,
CCK and GLP-1 and affect subjective appetite sensation scores.
Since CCK and GLP-1 are valid biomarkers of satiety and increased
levels of these hormones have been associated with reduced food
intake, PinnoThin™ TG and FFA may be effective in suppressing
appetite and a useful tool for weight management.
Acknowledgements
Many thanks to the investigators involved in the trials described
herein and to all the study volunteers.
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