The Waite Research Institute

 FOODplus Research Centre

                                           Scientific Seminar Ser...
Dr Tanya Little
University of Adelaide Discipline of Medicine
NHMRC Centre of Clinical Research Excellence (CCRE) in
Nutri...
   Gastrointestinal (GI) sensing of dietary fat
     Which factors determine the GI responses to
      dietary fat?

  ...
   There is a strong positive relationship
    between the intake of dietary fat with total
    energy intake and body we...
5000

4000
                      *
                      *
3000

2000

1000

   0
       Control       Fat       Glucose
 ...
   We examine downstream effects of fat
    sensing identified in cell line and animal
    studies. For example, changes ...
isolated pyloric
                     proximal gastric
pressure waves
                    relaxation
(IPPWs)
pyloric to...
small
inhibits energy          intestinal fat
intake
                  CCK, PYY, GL
                      P-1
            ...
triacyl-        monoacyl-
   glyceride        glyceride
                                      ↓ Food intake
              ...
9               CCK                                           IPPWs
         8                                            ...
IPPWs                                         CCK
         40                 *                            6

         30
...
40
                                                           Control
                                                    ...
45
Effectiveness in slowing




                           35
    gastric emptying




                           25

    ...
Pylorus                                  Energy intake
    120                              #        6000
    100
     80 ...
CCK                                      GLP-1
         16                                           30
         12       ...
PYY                                        Ghrelin
         50                                           500
             ...
vagotomy

        CCK1 receptor
         antagonist



CCK                     ↓ Gastric   ↓   Food Intake
               ...
60       Medulla                                60   Hypothalamus
%BOLD from baseline




                                ...
CCK                                                  Ghrelin
                               2100                          ...
10000                          ^
Energy intake (kcal)

                       8000
                                       ...
CD36                                      GPR120, GPR119, GPR40
free fatty acid (>C12)                    Gut peptides (CC...
CD36                                                GPR119
mRNA copy number




                                          ...
   FFAs are required for GI and appetite
    responses to fat
   Only FFAs with a chain length ≥12 are
    effective
  ...
   Recent evidence of a sixth “taste” modality
    responsive to oral free fatty acids (Chale-Rush et
    al., Chem Sense...
Energy intake                           Fat intake
     10000                                   40                     *
 ...
Fat taste threshold             Energy intake                          Fat intake
                           12           ...
Sensory detection threshold                                                    IPPWs
Detection threshold (mmol/L)




    ...
Oral detection        Habitual fat
          threshold             intake

IPPWs     R = -0.515            R = -0.532
    ...
   Individuals are able to sense or “taste”
    FFAs in the oral cavity
   There is large inter-individual variation in
...
   FFAs have potent effects on GI
    function, which favour suppression of
    energy intake
   Oral fat sensing appear...
   Need to determine:
     whether the GI responses to fat can be restored
     in obese individuals, e.g. by energy res...
   Assoc Prof Christine Feinle-Bisset
   Radhika Seimon
   Dr Richard Young
   Assoc Prof Chris Rayner
   Lena Brandl...
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Food and Satiety - part 1

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This FOODplus seminar was held by Drs Natalie Luscombe-Marsh and Tanya Little, both post-doctoral researchers from the School of Medicine. Natalie and Tanya both have an interest in understanding how the gut senses different macronutrients, and the differential effect of different macromolecules from the diet on gut function and satiety. We learnt that fat has a more significant and prolonged appetite-suppressing effect than carbohydrate, and that this effect is also influenced by fat type; that is, properties of different fats, like chain length and degree of saturation, can alter how they affect gastrointestinal function and the release of gut peptides. Natalie’s work focused more on the gastrointestinal sensing of protein, and Natalie presented preliminary results from a trial that is currently underway which aims to better understand the impact of protein on gut function and satiety. There is no doubt that understanding more about how different foods and different food components influence satiety is important when we are trying to determine the potential health benefits of different foods. The methods that were presented by Natalie and Tanya have enormous potential for helping us to understand how the novel food products developed within FOODPlus might influence how long feelings of fullness are maintained after a meal and the release of gut peptides which are critical for the regulation of appetite.

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Food and Satiety - part 1

  1. 1. The Waite Research Institute FOODplus Research Centre Scientific Seminar Series – 2010 #3a Dr Tanya Little Life Impact | The University of Adelaide
  2. 2. Dr Tanya Little University of Adelaide Discipline of Medicine NHMRC Centre of Clinical Research Excellence (CCRE) in Nutritional Physiology, Interventions and Outcomes
  3. 3.  Gastrointestinal (GI) sensing of dietary fat  Which factors determine the GI responses to dietary fat?  Oral detection of dietary fat  Relationships between: ▪ dietary fat intake and body weight ▪ oral and GI sensitivity
  4. 4.  There is a strong positive relationship between the intake of dietary fat with total energy intake and body weight (Golay and Bobbioni, Int J Obes Relat Metab Disord, 1997)  Obese individuals have an increased preference for high-fat foods (Mela and Sacchetti, AJCN, 1991)
  5. 5. 5000 4000 * * 3000 2000 1000 0 Control Fat Glucose * P<0.01 vs. control and glucose (Chapman et al. , AJCN , 1999)
  6. 6.  We examine downstream effects of fat sensing identified in cell line and animal studies. For example, changes in:  GI motility  plasma concentrations of GI peptides  food intake  Expression of fat sensing receptors in small intestinal biopsies
  7. 7. isolated pyloric  proximal gastric pressure waves relaxation (IPPWs) pyloric tone small  antral pressure intestinal waves fat  duodenal pressure waves slowing of gastric emptying (Seimon et al., AJCN, 2010)
  8. 8. small inhibits energy intestinal fat intake CCK, PYY, GL P-1 ghrelin slows gastric emptying (Seimon et al., AJCN, 2010)
  9. 9. triacyl- monoacyl- glyceride glyceride ↓ Food intake ↓ food intake + lipase inhibition (Orlistat) FFAs ↑ CCK, GLP-1, ↑ CCK, GLP- PYY 1, PYY ↓ gastric ↓ ghrelin ↓ ghrelin emptying Pancreatic and pancreatic and gallbladder gallbladder secretion secretion
  10. 10. 9 CCK IPPWs 8 90 7 A 70 6 pmol/l 5 50 P 4 30 3 10 2 D 1 * -10 mmHg 0 Fat Fat+orlistat 0 15 30 45 60 75 90 105 120 Time (min) Energy intake 6400 * 5600 Fat 4800 Fat+Orlistat (kJ) 4000 * P<0.05 vs. Fat kJ 3200 2400 1600 800 0 (Feinle et al., Am J Physiol Gastrointest Liver Physiol, 2003)
  11. 11. IPPWs CCK 40 * 6 30 4 Number pmol/l 20 * 2 10 0 0 -15 0 30 60 90 120 0 30 60 90 120 Time (min) Time (min) Control LE-0.26 µm * P < 0.05, LE-0.26 vs. control LE-30 µm LE-170 µm (Seimon et al., AJCN, 2009)
  12. 12. 40 Control LE-0.26 µm LE-30 µm Score (mm) 20 LE-170 µm 0 * -20 0 30 60 90 120 Time (min) * P < 0.05, LE-0.26 vs. control (Seimon et al., AJCN, 2009)
  13. 13. 45 Effectiveness in slowing 35 gastric emptying 25 15 5 -5 0 2 4 6 8 10 12 14 16 18 Number of carbon atoms in chain (Hunt & Knox, J Physiol, 1968)
  14. 14. Pylorus Energy intake 120 # 6000 100 80 4000 Total * 60 No. 40 2000 20 0 0 Control C10 C12 Control C10 C12 # vs control: P < 0.05 * vs control/C10: P < 0.05 (Feltrin et al., Am J Physiol Regul Integr Comp Physiol, 2004)
  15. 15. CCK GLP-1 16 30 12 * 20 * pmol/l 8 # 10 4 0 0 0 15 30 45 60 75 90 0 15 30 45 60 75 90 Time (min) Time (min) Control * vs. control/C10: P < 0.05 # vs. control P < 0.01 C10 C12 (Feltrin et al., Am J Physiol Regul Integr Comp Physiol, 2004)
  16. 16. PYY Ghrelin 50 500 450 40 * 400 pmol/l 30 350 300 20 250 * 10 200 0 15 30 45 60 75 90 0 15 30 45 60 75 90 Time (min) Time (min) Control * vs. control/C10: P < 0.05 C10 C12 (Feltrin et al., Peptides, 2006)
  17. 17. vagotomy CCK1 receptor antagonist CCK ↓ Gastric ↓ Food Intake emptying Small intestinal fat
  18. 18. 60 Medulla 60 Hypothalamus %BOLD from baseline %BOLD from baseline 50 50 40 40 30 30 20 20 10 10 0 0 Lipid + - + - Lipid + - + - Dex - - + + Dex - - + + (Lassman et al., Gastroenterology, 2010)
  19. 19. CCK Ghrelin 2100 ^ 270000 (pmol/l*180min) (pg/ml*180min) 1575 202500 * AUC AUC 1050 135000 525 * 67500 0 0 Saline LCFA LCFA Saline LCFA LCFA + Dex + Dex PYY 32000 * (pg/ml*180min) 24000 AUC 16000 8000 0 ^ P<0.05 ,LCFA+DEX vs. saline Saline LCFA LCFA * P<0.05, LCFA vs. saline + Dex (Degen et al. Am J Physiol Regul Integr Comp Physiol, 2007)
  20. 20. 10000 ^ Energy intake (kcal) 8000 * 6000 4000 2000 0 Saline C18 C18+Lox Treatment (Matzinger et al., Gut, 2000)
  21. 21. CD36 GPR120, GPR119, GPR40 free fatty acid (>C12) Gut peptides (CCK/GLP-1) apo A-IV/chylomicron Gut peptide receptors (e.g. CCK/GLP-1) lumen OA OEA ? PPAR-ɑ ? intestinal L-cell enterocyte intestinal I-cell vagal afferent vagal afferent (from Richard Young)
  22. 22. CD36 GPR119 mRNA copy number mRNA copy number 1.0 R2 = 0.59 0.0003 R2 = 0.34 0.8 P = 0.02 P = NS 0.0002 0.6 0.4 0.0001 0.2 0.0 0.0000 20 25 30 35 40 20 25 30 35 40 BMI (kg/m2) BMI (kg/m2) (Little et al., unpublished observations)
  23. 23.  FFAs are required for GI and appetite responses to fat  Only FFAs with a chain length ≥12 are effective  FFAs effects on GI function and energy intake are dependent on the CCK1 receptor  Expression of FA sensing receptors in the human SI may be related to BMI
  24. 24.  Recent evidence of a sixth “taste” modality responsive to oral free fatty acids (Chale-Rush et al., Chem Senses, 2007 et al.; Chale-Rush et al., AJP , 2007)  FA taste mechanisms analogous to those involved in intestinal fat sensing, e.g. CD36, GPR119, GPR120  Animal studies have revealed a relationship between oral sensing of dietary fat with fat preference (Pittman et al., Chem Senses, 2008; Gilbertson et al., Ann NY Acad Sci, 1998)
  25. 25. Energy intake Fat intake 10000 40 * 8000 * 30 6000 kJ % 20 4000 2000 10 0 0 Hyper Hypo Hyper Hypo Taste sensitivity Taste sensitivity N = 54 (12 hyper sensitive, 42 hyposensitive Mean BMI: 22.8 (0.8), range 16.8 – 29, kg/m2 * P < 0.05 vs. hypersensitive (Stewart et al., Br J Nutr, 2010)
  26. 26. Fat taste threshold Energy intake Fat intake 12 14000 120 * * Concentration C18:1 (mM) * * 10 12000 100 10000 8 80 Weight (g) 8000 kJ 6 60 g 6000 4 40 4000 2 2000 20 0 0 0 Lean Obese Lean Obese Lean Obese Lean Obese (Seimon et al., unpublished observations)
  27. 27. Sensory detection threshold IPPWs Detection threshold (mmol/L) Total no. IPPWs/90 min 15 80 R = -0.615 P = 0.00 60 10 40 5 20 R = 0.669 P = 0.002 0 0 20 25 30 35 40 20 25 30 35 40 BMI (kg/m2) BMI (kg/m2) N = 19 (10 lean, 9 obese) (Seimon et al., unpublished observations)
  28. 28. Oral detection Habitual fat threshold intake IPPWs R = -0.515 R = -0.532 P = 0.029 P = 0.028 CCK R = -0.430 R = -0.538 P = 0.075 P = 0.015 PYY R = -0.478, P = 0.045 (Seimon et al., unpublished observations)
  29. 29.  Individuals are able to sense or “taste” FFAs in the oral cavity  There is large inter-individual variation in taste thresholds for oleic acid  Individuals with lower sensitivity to oral fat have :  increased BMI  increased energy and fat intakes  impaired GI responses to intestinal fat infusion
  30. 30.  FFAs have potent effects on GI function, which favour suppression of energy intake  Oral fat sensing appears important in mediating dietary fat intake  Individuals who are less sensitive to oral FFAs have higher habitual fat, and energy, intakes and BMI  Individuals with decreased oral sensitivity to FFAs also appear to have impaired GI sensitivity
  31. 31.  Need to determine:  whether the GI responses to fat can be restored in obese individuals, e.g. by energy restriction  relationships between intestinal expression of fat sensing receptors with body weight, and acute and chronic nutrient exposure
  32. 32.  Assoc Prof Christine Feinle-Bisset  Radhika Seimon  Dr Richard Young  Assoc Prof Chris Rayner  Lena Brandlhuber Deakin University  Jessica Stewart  Dr Russell Keast

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