One of the main concerns about the healthiness of dietary fat is related to the growing problem of obesity, insulin intolerance and cardiovascular disease, which appear interrelated and are collectively identified as metabolic syndrome. Dietary fat contributes to the development of metabolic syndrome mainly because of its role in caloric overconsumption. This is primarily due to the high caloric value of fat in combination with the sensorial attractiveness of fat-rich foods and the relatively late satiety signal produced by fat. However, there is a quickly expanding field of recent insights that identifies different roles of specific fatty acids (such as saturated fatty acids, mono-unsaturated fatty acids and the essential omega-3 and omega-6 polyunsaturated fatty acids) for general health and metabolic syndrome in particular. This presentation shortly discusses recent insights in the factors that affect gastro-intestinal digestion, intestinal absorption and distribution through the body, and health implications of different fatty acids. Special attention is given to the physiological regulation mechanisms that control fat-induced satiety and caloric intake from food emulsions. In these systems fat digestion can be affected by the emulsifier through obstruction of the digestive enzymes and by colloidal destabilization processes (aggregation and coalescence) in the stomach. Based on these insights opportunities are be identified for a healthier fat formulations.

1. How fat composition
and food formulation
affect absorption and
mediate food intake
Which way to go? George van Aken
george.vanaken@nizo.nl
Monday, September 26, 2011
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2. Key question
Fat is highly caloric, sensorially pleasant food
constituent which entices overeating
How can we avoid overeating?
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3. Origin of the study
Finalized project at TIFN:
Engineered Sensory and Dietary Functionality of Dispersed
Fat
• Project goals:
• Optimization of fat-related sensory and dietary effects.
• Main focus on satiety and food intake reduction.
• Key objectives:
• Gastro-intestinal behaviour of food emulsions in relation to physiological
responses.
• Physical-chemical and biochemical mechanisms behind this behaviour.
• Engineering rules to help control the processing, delivery and release of fat
in the digestive tract.
NOW focussing on application at NIZO food research
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4. Outline
• Fundamentals of fat digestion and absorption
• Role of fat consumption in obesity
• How can we reduce caloric intake?
• Conclusions
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5. FUNDAMENTALS OF FAT
DIGESTION AND ABSORPTION
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6. Emulsion digestion and absorption
Digestion
processes
lipases bile Regulation of
digestion and food
intake
Fatty acid
absorption Delivery of
-3, -6 and vitamins

7. Fat digestion: main enzymatic processes
Stomach
Gastric lipase
(<10%)
blood
Small Small intestinal
intestine wall Short chain and
polunsaturated FFA Serum
albumin
transporter
Pancreatic lipase
(almost complete) Fast
LCFA
chylomicron
Slow
lymph
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8. Routing of fatty acids - overview
Nerve membrane
Functional
liver
lipids FA
glucose
Portal vein
C11:0 and shorter
Main ω-3 DHA
blood
ω-6 serum VLDL stream
albumin
ω-3
glucose LDL
chylomicrons
Oleic acid
C12:0 and longer Lymph vessel
Energy
supply Muscles Adiposites

9. ROLE OF FAT CONSUMPTION
IN OBESITY
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10. Positive energy balance
METABOLIC SYNDROME:
Type II diabetes, OBESITY,
Inflammatory reactions, high
blood pressure,
atherosclerosis, CVD
Enlarged adipocytes: Ectopic fat storage in:
Fat storage exceeds • Impared adiposite • liver
differentiation and • heart
the normal storage function • pancreatic β-cells
capacity of adiposites • Modulated • skeletal muscle,
endocrine fuction • abdominal fat
Heilbron et al, Int. J. Obesity, (2004)

11. Ease of overeating of fat
Nutrient Caloric Sensory effect Ease of
value overeating
(kcal/g)
Proteins 4 Can be relatively unpleasant : small
tends to a highly viscous, tough and dry
mouthfeel
Sugars 4 Pleasant : moderate
viscous mouthfeel
sweet
Fats 9 Pleasant: high
thin mouthfeel, lubricant, smoothening
adds to flavour richness
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12. BUT: the body is designed for efficient
absorption and to control food intake
duodenum jejunum ileum
Pylorus absorptive cells
Stomach
intake Stomach Small intestine
emptying
gall
bladder pancreas
COLON
Feedback
Detailed in vivo human study to confirm these feedback mechanisms are
still ongoing at TIFN in collaboration with Maastricht University

13. Nutrient transport through the
gastrointestinal tract is regulated
Physiological restrictions:
• Vmax per unit length of small intestine
• Absorption requires transfer from polymers to monomers:
• proteins amino acids
• di-, oligo-, polysaccharides monosaccharides
• triglycerides fatty acids, monoglycerides
Regulation mechanism for efficient absorption:
• Efficient and gradual absorption of nutrients by small intestine
• > 95 % for a single shot of 650 g oil (220% of advised total daily caloric intake)
• Small intestinal transit time adjusted to avoid spill over into the colon
Regulation mechanisms for food intake:
• Feeling of a full stomach
• related to gastric distension + the detection of nutrients in the small intestine
• Feeling of hunger
• related to a low reserve of nutrient in small intestine

14. Some main feedback mechanisms
Van Aken, Food Biophysics (2010) 5(4):258–283
Full stomach
duodenum jejunum ileum
Meal
ending - Computer
intake
max
storage modelling
Pylorus Transit speed
Fed by: physiological literature
- bile vitro studies
in pancreas
GLP-1
-
Next (Belly Quintet, Symphid, TIM)
meal
- I-cells L-cells
CCK
CCK PYY,
No + GLP-1
hunger CCK-B
Large reservoir of nutrient
+ present in small intestine

15. HOW CAN WE REDUCE THE
CALORIC INTAKE?
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16. 1. Increase feeling of a full stomach during
eating by reducing the initial fast emptying
• Gastric emptying of non-nutritional liquid is fast and
dependent on the viscosity
• Gastric emptying of nutritious liquids is much slower and
regulated at a constant release of energy (~ 2 kcal/min)
• Regulation only starts after sufficient nutrients have
entered the small intestine. This may take several minutes.
• Fullness is however dependent on both gastric distension
(increased) and nutrient detection in the small intestine
(lowered)
Simulation of an
emulsion of 30 g fat
and 200 g water;
effect of a 1000x
increase in viscosity

17. 2. Keep a full stomach during eating by
control of emulsion stability
• Gastric emptying of nutritious liquids regulated at a
constant release of energy (~ 2 kcal/min)
• Bulk fat and many emulsions and are unstable in the
stomach (low pH, enzymes) and phase separate into
an energy- rich creamed layer (containing the fat)
Marciani et al. 2009 *
and an energy-poor lower phase *
• Consequence: the energy poor lower phase empties fast, quickly
reducing the volume of the stomach
• Felt as less fullness during and shortly after the meal.
Simulation of an emulsion of 30 g
fat and 200 g water; effect of fat
floating until fundus and corpus
have emptied (50 ml water)
*Marciani et al., British Journal of Nutrition (2009), 101, 919–928

18. Approach: inverted phase separation in
stomach
A number of sedimenting emulsion systems
have been identified*
5 % triolein, 1 % WPI,
1 % caseinate
CURRENTLY investigated in an in vivo human trial
(TIFN, IFR, (2) Norfolk and Norwich University hospitals NNUH)
Expectation: Gastric volume reduces slowly → more fullness
during a meal → sooner meal ending
Full fat milk
Simulation of an emulsion of
30 g fat and 200 g water;
effect of fat sedimentation until
5 ml of fat is left in the antrum
* Van Aken, G.A., Bomhof, E., Zoet, F.D., Verbeek, M., Oosterveld, A., Food Hydrocolloids (2011), 25: 781-788,
Differences in in vitro gastric behaviour between homogenized milk and emulsions stabilised by Tween 80, whey protein, or whey protein
and caseinate

19. 3. Control the rate of intestinal fat hydrolysis
Small intestinal transit time normally regulated to compensate for
a high caloric entry into the intestine or slow enzymatic hydrolysis
(“Ileal brake”)
Sugars delivered to the ileum or fat delivered to the jejunum shortly (e.g.
15 min) before a meal reduces food intake from that meal.
Compensates only; no effect on total caloric intake.
Simulation of an
emulsion of 30 g fat
and 200 g water;
effect of a 10x
slower digestion

20. 4. Reduce the rate of intestinal
absorption of fat hydrolysis products
• Oleic acid or oleic acid + monoolein intubated into the jejunum gives a
strong hunger suppressing signal
(Little et al., Am. J. Physiol.2005)
• A similarly strong effect is also found for 1,3 diglycerides
(Kristensen et al., J. Nutrition 2006; Yanai et al., Nutrition Journal, 2007)
• Stronger effect of predigested TG, oleic acid and 1,3-diglycerides also
reduces total caloric intake (overcompensation).
The excess suppression by oleic acid seems only to occur beyond a
higher level of free oleic acid intubated
(Woltman & Reidelberger, Am. J. Physiol. 1995).

21. Possible explanation of stronger effect of
predigested TG, oleic acid and 1,3-diglycerides
ENTEROCYTE
Portal
Pancreatic vein
lipase
absorption
glycerol-3-phosphate
pathway
SLOW
Fullness Fatty acid chylomicron
Food intake receptor
reduction ENTEROCYTE
absorption
monoglyceride
Pancreatic pathway
lipase Lymph
FAST
vessel
Kristensen et al., J. Nutrition 2006

22. Simulated effect of slower intestinal
absorption
Most effective fat-based way to reduce hunger and
food intake?
Replace TG by fatty acids, diglycerides,
monoglycerides, non-glyceride esters
Simulation of an
emulsion of 30 g fat
and 200 g water;
effect of a 4x
slower absorption

23. CONCLUSIONS
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24. summary
Fat is highly caloric, sensorially pleasant food
constituent which entices overeating
How can we avoid overeating?
Lipids are also satiating and can be used to
limit food intake, but it needs to be in an
appropriate form or type
Opportunities for product development!
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25. Optimized formulations of fat/lipids in food may help to
• Reduce the over-eating during a liquid meal:
• Avoid fat creaming in the stomach (acid and pepsin stable
emulsifiers) (ongoing in vivo human study)
• Induce gastric sedimentation of fat (dense fat structures)
(ongoing in vivo human study)
• Decrease hunger and suppress intake on next meal:
• Increase the viscosity (however less fullness during the 1st meal)
• Marginal effect of slower digestion (emulsifiers that slow release
of FA)
• Large effect by slower absorption:
• Replace TG by fatty acids, diglycerides,monoglycerides, non-
glyceride esters
• Release system of encapsulated fatty acids, diglycerides, non-
glyceride esters fatty acids
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26. Let’s translate:
Opportunities for product development
Belly Quintet
Animal Model
Food grade
pilot plant
Human SYMPHID
subjects
Computer
modelling
Tiny TIM
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