Investigations Into The Gastrointestinal Control Of Appetite And Food Intake

266 Pages·2015·14.39 MB·English

by  Rosalie Vozzo

t
r-.rr
INVESTIGATIONS INTO THE GASTROINTESTIN
CONTROL OF APPETITE AND FOOD INTAKE
A thesis submitted by
Rosalie Yozzo
For the degree of
Doctor of PhilosoPhy
Department of Medicine
University of Adelaide
June 2002
TABLE OF CONTENTS
xvl
Thesis summary
Statement of originalitY xlx
Dedication XX
xxi
Acknowledgements
xxiv
Publications
1
Chapter APPETITE AND DISEASE
1.1 Introduction 1
I
1,2 Obesity
1.2.I Epidemiology 2
L.2.2 Etiology of overweight and obesity J
L.2.3 Obesity and associated health risks t2
1.3 Anorexia nervosa T3
1.3.1 Definition and epidemiology L4
1.3.2 Perceptions of food in anorexia nervosa T4
1.3.3 Appetite-related symptoms in anorexia nervosa 15
I.3.4 Appetite-regulating peptides 15
1.4 Anorexia of ageing 16
1.4.I Epidemiology t7
L.4.2 Sensory percePtion I7
1.4.3 Gut-peptide release 18
I.4.4 læptin T9
L4.5 Central appetite-regulating pathways 19
1.5 Conclusion 19
chaprer 2 REGIILATION OF APPETITE AND FOOD INTAKE
2.r Introduction 2T
2.2 Central mechanisms controlling food intake 2T
2.2.I Neuroanatomical sites 22
ll
2.2.2 Chemical mediators 23
2.3 Peripheral mechanisms 26
2.3.1 Common gastrointestinal tract anatomy 2l
2.3.2 Stomach 29
2.3.3 Pylorus 33
2.3.4 Small intestine 34
2.3.5 Gastrointestinal PePtides 38
2.4 Conclusion 46
Chapter 3 DIETARY MACRONUTRIENTS AND THEIR COMPARATIVE
EFFECTS ON APPETITE AND FOOD INTAKE
3.1 Introduction 48
3.¿ Macronutrient satiating hierarchy 49
3.2.L Dietary interventions and pre-loading studies 49
3.2.2 Time course of effects 50
3.2.3 Implications for weight loss 52
3.3 Characteristics of foods affecting satiety 53
3.3.I Sensory properties of food 53
3.3.2 Volume and weight 54
3.3.3 Energy density 55
3.3.3 Frequency of feeding 56
3.4 Conclusion 59
Chapter 4 EFFECTS OF MONOSACCHARIDES ON GLYCEMIC
CONTROL AND APPETITE RE,GULATION IN HEALTHY
INDIVIDUALS AND IN PATIENTS WITH NON.INST]LIN
DEPENDENT DIABETES MELLITUS
4.I Introduction 60
4.2 Fructose in the diabetic diet 6T
4.2.I Glycemic control 6t
4.3 Monosaccharide absorPtion 62
lll
4.3.I Monosaccharide transporters 62
4.3.2 Glucose transPort 64
4.3.3 Fructose transPort 64
4.4 Effects of monosaccharides on appetite 65
4.4.1 Comparative satiating efficiencies of monosaccharides 65
4.4.2 Peptide hormones 61
4.5 Metabolic responses to monosaccharide ingestion 68
4.5.T Blood glucose 68
4.5.2 Peptide hormones 68
4.6 Conclusion 70
Chapter 5 THE ROLE OF NITRIC OXIDE MECHANISMS IN TIIE
REGULATION OF MAMMALIAN FEEDING BEHAYIOUR
7I
5.1 Introduction
7l
5.2 Nitric oxide physiologY
5.2.I Endogenous NO Production 7l
5.2.2 Nitric oxide synthase localisation 72
5.2.3 Cellular targets of NO 73
5.2.4 Physiological functions of NO 74
5.3 Nitric oxide and food intake 14
5.3.1 Nitric oxide antagonists and food intake 74
5.3.2 Nitric oxide synthase inhibition in genetically obese animals 75
5.3.3 Effects of food deprivation on NO production 75
5.3.4 Non-specific effects of NOS antagonists 76
5.4 Mechanisms regulating NO synthase inhibition-induced anorexia 76
5.4.1 Central mechanisms 16
5.4.2 Peripheral mechanisms 77
79
5.5 Conclusion
6
Chapter COMMON METHODOLOGIES
6.1 Introduction 81
lv
6.2 Subjects 81
6.3 Ethics approval 82
6.4 Study environment 82
6.5 Drug preparation and administration 83
6.6 Preload preparation and administration 83
6.6.I Yoghurt Pre-loads 83
6.6.2 Triglyceride emulsion 84
84
6.1 Techniques
6.1 J Assessment of feeding behaviour 84
6.7.2 Blood samPling 88
6.7.3 Haemodynamic variables 88
6.7 .4 Biochemical variables 89
6.7.5 ManometrY 90
92
6.8 Statistical analyses
Chapter 7 THE EFFECTS OF INCREASED DIETARY PROTEIN ON
SATIETY ARE ATTENUATED BY FAT
94
7.1 Summary
94
7.2 Introduction
95
7.3 Method
7.3.1 Subjects 95
7.3.2 Protocol 96
7.3.3 Macronutrient preloads and buffet meal 97
7.3.4 Appetite sensations 91
.3.5 Biochemical variables 91
7
7.3.6 Statistical analYses 97
97
1.4 Results
7.4.I Subjects, baseline diets and blinding of preloads 98
7.4.2 Appetite sensations 98
7.4.3 Energy and macronutrient intakes 99
7.4.4 Plasma glucose and insulin 99
7.4.5 Plasma free fattY acids 100
100
7.5 Discussion
Chapter 8 HIGH PROTEIN, HIGH CARBOHYDRATE AND HIGH FAT
YOGHIJRT PRE.LOADS AND THEIR EFFECT ON
SI.]BSEQI.IENT SPONTANEOUS FOOD INTAKE IN HEALTHY
ST]BJECTS
8.1 Summary 108
8.2 Introduction 108
8.3 Methods r09
8.3.1 Subjects 109
8.3.2 Protocol 109
8.3.3 Yoghurt preJoads 110
8.3.4 Buffet meal 110
8.3.5 StatisticalAnalyses 110
8.4 Results 111
8.4.1 Yoghurtpre-loads 111
tt2
8.4.2 Food intake
8.4.3 Timing and size of eating episodes t12
8.4.4 Macronutrient intake 113
tt3
8.4.5 Appetitesensations
8.5 Discussion 113
chaprer 9 EFFECT OF MEAL FREQUENCY ON FOOD INTAKE
r22
9.1 Summary
9.2 Introduction r22
t23
9.3 Methods
9.3.1 Subjects 123
9.3.2 Protocol t23
9.3.3 Pre-loading schedule t24
9.3.4 Pre-load composition t24
9.3.5 Test meals t25
9.3.6 Statistics t25
vl
9.4 Results 126
9.4.L Blood glucose 126
9.4.2 Appetite sensations 126
9.4.3 Food intake 127
9.5 Discussion 727
Chapter 10 ANTROPYLORODUODENAL, CHOLECYSTOKININ AND
FEEDING RESPONSES TO PI]LSATILE AND NON.PULSATILE
INTRADUODENAL LIPID INFUSION
t37
10.1 Summary
ro.2 Introduction 138
r39
10.3 Methods
r39
10.3.1 Subjects
r39
IO.3.2 Protocol
10.3.3 Measurement of antropyloroduodenal pressures t40
lO -3.4 Quantification of plasma cholecystokinin 140
10.3.5 Assessment of appetite and food intake 140
t40
10.3.6 Statistical analyses
141
ro.4 Results
10.4. 1 Antropyloroduodenal pressures 141
tO.4.2 Plasma cholecYstokinin 742
t42
IO.4.3 Appetite and food intake
t43
10.5 Discussion
Chapter 1L GLYCEMIC, HORMONE AND APPETITE RESPONSES TO
MONOSACCHARIDE INGESTION IN PATIENTS WITH TYPE 2
DIABETES
t52
1 1.1 Summary
tL.2 Introduction 153
1 1.3 Methods 154
t54
11.3.1 Subjects
vll
LL3.2 Protocol 154
LL.3.3 Biochemical measurements 155
LL.3.4 Assessment of aPPetite 155
11.3.5 Statistical analYsis 155
II.4 Results t56
LI. .I Biochemical measurements 156
L7.4.2 Appetite and food intake 158
11.5 Discussion 159
Chapter 12 EFFECT OF INTRAVENOUS ADMINISTRATION OF NITRIC
oxIDE (NO) SYNTHASE rI\HIBITORS, L-NMMA AND L-
NAME, ON SHORT-TERM APPETITE AND FOOD INTAKE IN
HT]MANS
t2.l Summary 771
t72
t2.2 Introduction
t2.3 Methods 172
12.3.1 Subjects 172
t72
L3.3.2 Protocol
13.3.3 Statistical AnalYses 174
t74
12.4 Results
12.4.1 Effects of L-NMMA and L-NAME on blood pressure and heart rate 174
fl6
12.4.2 Effect of L-NMMA and L-NAME on sensations of appetite and on
food intake
t2.5 Discussion 176
Chapter 13 EFFECTS OF NITRIC OXIDE SYNTHASE INHIBITOR NG.
NrTRO-L-ARGINTNE (L-NAME) ON
ANTROPYLORODUODENAL MOTILITY AND APPETITE IN
RESPONSE TO INTRADUODENAL LIPID INFUSION IN
HUMANS
L3.I Summary 185
viii
13.2 Introduction 186
13.3 Methods 187
r87
13.3.1 Subjects
13.3.2 Protocol 187
13 .3 .3 Measurement of antrop yloroduodenal pre s sures 188
13.3.4 Statistical analYsis 188
13.4 Results 188
13.4.L Antropyloroduodenal pressures 188
13.4.2 Appetite and food intake 189
13.5 Discussion 189
14
Chapter CONCLUSION 198
APPENDIX
A 1 Three-daY diet diarY 202
A2 questionnaires 206
Visual analogue
A 3 Energy content and macronutrient composition of foods served as buffet lunch 208
4 placement 209
A Manometric catheter and
2r0
REFERBNCES
lx
LIST OF FIGURES
2.r Central sites involved in the regulation of appetite and food 22
intake
2.2 Peripheral factors affecting appetite and food intake 28
30
2.3 Stomach anatomY
7.1 Hunger, fullness and desire to eat following ingestion of 103
yoghurt high in fat, protein, carbohydrate and protein / fat
1.2 Energy intake at a buffet meal following ingestion of yoghurt 105
high in fat, protein, carbohydrate and protein / fat
LJ Plasma glucose and insulin concentrations following 106
ingestion of yoghurt high in fat, protein, carbohydrate and protein / fat
7.4 Plasma free fatty acid concentrations following ingestion of 107
yoghurt high in fat, protein, carbohydrate and protein / fat
8.1 Spontaneous energy intake following ingestion of yoghurt 120
high in fat, protein and carbohydrate
8.2 Energy intake per eating episode and number of eating Lzt
episodes following ingestion of yoghurt high in fat, protein and
carbohydrate
9.1 Blood glucose concentrations following mixed-nutrients pre- 135
loads differing in frequency of administration
9.2 Hunger and nausea following mixed-nutrients pre-loads t36
differing in frequency of administration
10.1 Antropyloroduodenal pressure wave activity following t48
pulsatile intraduodenal lipid infusions
ro.2 Antropyloroduodenal pressure wave amplitudes following 149
pulsatile intraduodenal lipid infusions
10.3 Plasma cholecystokinin concentrations following pulsatile 150
intraduodenal lipid infusions
70.4 Fullness, hunger and nausea following pulsatile 151
intraduodenal liPid infusions
1 1.1 Blood glucose concentrations following fructose ingestion in 165
diabetics
It.2 Plasma insulin concentrations following fructose ingestion in r66
diabetics
x