Feeding behaviour Flashcards
(156 cards)
1
Q
How is Body Mass Index BMI defined
A
Mass (kg) /(height (m))^2
2
Q
What BMI range is considered obese
A
BMI>30kg/m2
3
Q
What is body mass a balance between
A
Energy intake and energy expenditure
4
Q
How can weight loss be achieved
A
Reducing food intake and increasing energy expenditure
5
Q
What are potential strategies to reduce energy intake for anti-obesity treatment
A
Diet- reducing amounts, non-nutritious food, targeting the urge to eat, inhibiting fat nutrient absorption, reducing capacity to eat
6
Q
What are potential strategies to enhance energy expenditure for anti-obesity treatment
A
Exercise- burning energy at a cellular level, stimulating BAT thermogenesis, stimulating fat mobilization
7
Q
What is Basal Metabolic Rate BMR
A
A measure of energy expenditure including calories needed to stay alive
8
Q
When is BMR recorded
A
In the fasted state at rest
9
Q
Why is male BMR higher than female BMR
A
Due to higher muscle mass
10
Q
What historical method targeted BMR in the 19th century to increase it
A
Thyroid hormone
11
Q
What historical method targeted BMR in the early 20th century by producing heat from mitochondria
A
Dinitrophenol DNP
12
Q
What historical method activated metabolism enhanced expenditure and reduced intake
A
Sympathicomimetics like Amphetamines
13
Q
What triggers energy intake
A
Negative energy balance habit palatability social pressure
14
Q
What determines meal size
A
Portion size available satiation signals cognitive restraint
15
Q
What are potential drug effects on energy intake
A
Delaying initiation of a meal reducing portion size eating slower inducing nausea
16
Q
Most anti-obesity drugs to date have targeted which system
A
The monoamine systems mainly 5-HTR
17
Q
How did many anti-obesity drugs originate
A
From side effects observed with psychotropic drugs
18
Q
What is the mechanism of Thyroid extract as an anti-obesity drug
A
Increased energy expenditure
19
Q
What is the mechanism of Dinitrophenol as an anti-obesity drug
A
Mitochondrial uncoupler
20
Q
What is the mechanism of Amphetamine as an anti-obesity drug
A
Sympathicomimetic
21
Q
What is the mechanism of Fenfluramine as an anti-obesity drug
A
Increases 5-HT release and reduces reuptake
22
Q
What is the mechanism of Orlistat as an anti-obesity drug
A
Gastric lipase inhibitor affecting nutrient uptake
23
Q
What is the mechanism of Rimonabant as an anti-obesity drug
A
Cannabinoid CB1 receptor antagonist acting on hunger receptors
24
Q
What is the mechanism of Lorcaserin as an anti-obesity drug
A
5-HT2c receptor agonist
25
What is the mechanism of Bupropion as an anti-obesity drug
NA and DA reuptake inhibitor
26
What new approach is needed for anti-obesity treatment
Combination drugs
27
What is an advantage of combination drugs for anti-obesity treatment
Can target two systems delivering larger effects lower individual doses reduce side effects
28
What is an example of a combination drug approach mentioned
Bupropion with a µ κ opioid receptor antagonist
29
Until recently what was the only anti-obesity drug not withdrawn from the market due to side effects
Orlistat
30
What is a reason for low compliance with Orlistat
Unpleasant gastric effects
31
What are major risks associated with anti-obesity drugs
Cardiovascular risks increased risk of cancer unpleasant gastric effects
32
What is a key issue with anti-obesity drugs leading to withdrawals
Insufficient selectivity
33
Which drug caused Valvulopathy due to 5-HT action on 5-HT2b receptors leading to its withdrawal
Fenfluramine
34
How is energy homeostasis regulated
By the brain integrating signals from long-term energy stores and short-term meal-related signals
35
What do these brain inputs modulate
The reward value assigned to food and determining intake and risk taken to obtain food
36
What did lesion of the ventromedial hypothalamus suggest in early animal experiments
Hyperphagia and obesity suggesting it was a satiety center
37
What did lesion of the lateral hypothalamus suggest in early animal experiments
Reduced food intake and bodyweight suggesting it was a feeding center
38
What did injection of glucose antimetabolites into the 4th ventricle induce suggesting brainstem involvement
Feeding
39
Which peripheral mediator signals adipose tissue energy stores
Leptin
40
How does Leptin act via adiposity feedback
Stimulates POMC neurons inhibits NPY neurons in the hypothalamus stimulates GLP-1 neurons in the brainstem
41
Which peripheral mediator is a meal termination signal caused by enlargement of the stomach
Gastric distention via vagal nerve activation
42
Which peripheral mediator is a meal termination signal released in the gut
Cholecystokinin CCK
43
Which peripheral mediator is an incretin
Glucagon-like peptide-1 GLP-1
44
Which peripheral mediator is released from β-cells and acts on AP to increase satiation
Amylin
45
Which peripheral mediator decreases food intake by acting on Y2 receptors
Peptide YY PYY
46
Which mediators or signals increase food intake
Ghrelin and Hypoglycaemia
47
Which orexigenic factors inhibit POMC neurons and act as agonists on Y1 and Y5 receptors reducing energy expenditure reducing satiety and increasing lipogenesis
Neuropeptide Y NPY and Agouti-Related Peptide AgRP where NPY is the agonist on Y1 and Y5
48
Which orexigenic factor is an inverse agonist on melanocortin receptors and reduces energy expenditure
AgRP
49
What are other orexigenic factors mentioned
Endocannabinoids Orexin Hypoglycaemia
50
Which anorexigenic factor acts on 5-HT2c receptors 5-HT1b receptors and 5-HT3 receptors
Serotonin 5-HT
51
How do Melanocortins from POMC neurons affect food intake and energy expenditure
αMSH reduces food intake increases energy expenditure
52
Activation of which receptors in various brain regions reduces intake and is supported by GWAS findings
MC4 receptors
53
What effect was seen with MC4 agonists in clinical trials and what was a side effect
Modest weight reduction and stimulating the sympathetic nervous system affecting blood pressure
54
What effect does Baclofen a GABAB agonist have on weight in humans
Causes modest weight loss
55
What is crucial to prevent anorexia regarding GABAergic input
GABAergic input from NPY neurons onto PBN
56
What are other anorexigenic factors mentioned
Noradrenaline NA Nicotine GLP-1 Dopamine DA
57
How does Dopamine D1 receptor in striatum affect intake
Increases intake of palatable food
58
How does Dopamine D2 receptor stimulation affect intake
Reduces intake
59
What type of drugs are desired for an ideal central anti-obesity treatment
Pathway-specific drugs
60
Why are pathway-specific drugs desired
To minimize peripheral side-effects
61
What are potential central drug targets mentioned
GLP1 analogue CCK receptor agonists 5-HT1b agonist 5-HT2c agonist MC4 receptor agonists
62
What was observed in a rat experiment with automated infusion of CCK-8 at the beginning of each meal
Meal sizes reduced but the number of meals increased
63
What did the CCK-8 rat experiment imply
That another signal counteracts CCK-8 to obtain necessary intake
64
What effect was observed in the Orlistat study in the first 4 weeks for all groups
Strong placebo effect
65
What did the strong placebo effect in the Orlistat study show
Motivation to lose weight
66
When was the weight loss effect of Orlistat seen after the placebo effect
After 4 weeks until week 36
67
What happened to the weight of the Orlistat group after reaching maximum weight loss at week 36
It increased from the maximum loss achieved
68
What might the weight increase after maximum loss in the Orlistat group represent
A decline in motivation and change in lifestyle
69
What is important for anti-obesity treatment regarding patient progress
Motivation and positive feedback after seeing weight loss
70
What happened to the weight of the Lorcaserin group that switched to placebo in year 2
The weight went back up to match the placebo group
71
What did the Lorcaserin study show regarding the cause of weight loss
The weight loss was due to the drug
72
Even with the drug Lorcaserin what is seen emphasizing motivation and reward
Some rebound
73
What percentage of weight loss is usually achieved by anti-obesity medication
0.05
74
What question is raised about the weight loss achieved by medication
If it meets patient expectations
75
What is an alternative to drugs usually for morbidly obese patients
Gastric bypass surgery
76
What are the mechanisms of gastric bypass surgery
Restrictive malabsorptive endocrine effects
77
How does Roux-en-Y gastric bypass surgery work
Part of the stomach and duodenum removed from pathway alimentary limb connected to mid-jejunum absorption reduced
78
How does Sleeve gastrectomy surgery work
Part of the stomach removed unaltered route for nutrients less food consumed
79
How does gastric bypass compare in effectiveness to sleeve gastrectomy and drugs
Less effective than sleeve gastrectomy but more effective than drugs
80
Are fasting GLP-1 levels altered after gastric bypass procedures compared to obese patients with similar weight loss from diet or gastric band
No they are not altered
81
When are enhanced postprandial GLP-1 responses observed after gastric bypass surgery
As early as 1 to 3 days postoperatively
82
Which type of gastric bypass has a greater enhancement of postprandial GLP-1 response
Roux-en-Y gastric bypass approximately x5 enhancement
83
How much is the postprandial GLP-1 response enhanced after sleeve gastrectomy
Approximately x3 enhancement of preoperative response
84
Was the enhanced GLP-1 response observed in obese patients who were calorically restricted
No this was not observed
85
What happens to the GLP-1 response during the first postoperative year after gastric bypass
There is usually a progressive increase
86
Do the enhanced GLP-1 responses persist in the long term after gastric bypass
Yes they persist
87
How do these changes in GLP-1 secretion contrast with GIP secretion after gastric bypass
GIP secretion is relatively unaltered
88
What are examples of incretin mimetics or GLP-1 analogues used as treatments
Liraglutide and semaglutide
89
Why do GLP-1 analogues need to be injected
These peptides would be digested in the digestive systems
90
What are advantages of GLP-1 analogues
Improve glycaemic control low risk of hypoglycaemia cause sustained weight loss
91
What is a common side effect of GLP-1 analogues
Nausea
92
What are DPP-4 inhibitors also called
Gliptins
93
What does the enzyme DPP-4 do
It inactivates GLP-1
94
How do DPP-4 inhibitors like Sitagliptin and Saxagliptin work
They increase the half-life of gut-released GLP-1 in the circulation
95
What are advantages of DPP-4 inhibitors over Incretin mimetics
Good effect on diabetes oral drugs fewer side effects difficult to overdose
96
What are differences between DPP-4 inhibitors and Incretin mimetics regarding effects
DPP-4 inhibitors have no effect on gastric emptying no effect on satiety no weight loss
97
Are DPP-4 inhibitors specific for GLP-1
No they are not specific for GLP-1
98
What do treatments with GLP-1 analogues appear to mimic
Some effects of gastric bypass surgery
99
As of 2022 what did NICE draft guidance recommend Semaglutide for
Anti-obesity treatment for those with BMI 35kg m2
100
What is a main conclusion about using neurotransmitters or their receptors as targets for weight-loss drugs
It is difficult because of side effects
101
What is a main conclusion about the amount of weight-loss achieved by pharmaceutical intervention
It is usually small
102
What is concluded about the placebo effect in weight loss interventions
The placebo effect is significant
103
What is currently the most effective procedure to achieve sustained substantial weight-loss
Gastric bypass
104
How does a maintained calorie-restricted diet compare to surgery for weight loss
It achieves the same weight loss as surgery
105
What might targeting circulating factors involved in appetite control mimic
Some effects of bariatric surgery
106
What are currently the most effective options among targeted circulating factors
GLP-1 mimetics
107
What development would be useful for GLP-1 based treatments
Development of non-peptide oral GLP-1R agonists
108
How is the field of anti-obesity treatment evolving rapidly
With combination treatments
109
What must all anti-obesity interventions be combined with to achieve and maintain a healthy weight and life
Sustained life-style changes increased exercise calorie balanced diet
110
What does the common side effect of nausea with GLP-1 analogues raise questions about
How these drugs achieve reduced food intake
111
What distinction is important when considering reduced food intake
Distinguishing between reduced appetite and malaise
112
What do satiety signals integrate with
Hunger and reward
113
What is stress-induced anorexia
A phenomenon where factors like threat noxious substances cancer cachexia or neophobia override homeostatic control of food intake
114
What is an example of stress-induced anorexia mentioned
Conditioned taste aversion CTA
115
Which neurons act like an off-switch and mediate stress-induced anorexia
CGRP neurons
116
What is a potential issue with targeting stress-induced anorexia mechanisms
It might have other unwanted side effects via the adrenergic system
117
Where do pitfalls exist in pre-clinical research regarding feeding behaviour
When translating findings from animals to humans
118
How do humans and rodents consume most food
In discrete episodes called meals
119
How many meals do humans typically eat per day and during which phase
3-4 meals during the day light phase
120
How do mice rats consume meals
More frequent smaller meals ~70% during the night dark phase
121
Can rodent meal patterns be entrained to mimic humans
Yes mice can be easily meal-entrained
122
What is the predictive validity of rodent feeding studies for human behaviour
Relatively high
123
What is important for elucidating the neurobiology of feeding using modern neuroscience techniques in rodents
Using appropriate behavioural analyses
124
How is a meal defined in feeding studies
A cluster of feeding events separated by short non-feeding intervals with clusters separated by longer inter-meal intervals and a minimum cluster size
125
What are methods to measure feeding behaviour
Quantification of Food Intake and Observational Analysis
126
What are methods for quantifying food intake
Manual food weighing automated scales pellet dispensers
127
What are methods for observational analysis of feeding behaviour
Behavioural Satiety Sequence BSS Conditioned Taste Aversion CTA
128
What are pros of Manual Food Weighing
Cheap and easy objective consistent
129
What are cons of Manual Food Weighing
No meal pattern data hourly weighing is disruptive requires presence during the dark phase
130
What information is missed by total or hourly manual weighing
Important details measuring just the endpoint
131
What are pros of Automated Scales
Automated recording calculation of meal pattern data can use normal chow can combine with calorimetry activity good for long-term phenotyping
132
What are cons of Automated Scales
Very expensive false positives from hopper interactions common temporal resolution not very good
133
What are pros of Pellet Dispensers
Very precise temporal and quantity data for meal pattern analysis open-source versions can be built cheaply placed in home cage easily combined with video analysis
134
What are cons of Pellet Dispensers
Special pellets needed regular maintenance for reliability
135
What is the Behavioural Satiety Sequence BSS
Species-specific behavioural sequence of natural satiation satiety eating grooming resting
136
How does BSS help distinguish primary anorexia from secondary behavioural effects
Primary anorexia accelerates transition but maintains sequence secondary effects disrupt sequence
137
What are examples of secondary effects that suppress intake and disrupt the BSS sequence
Sedation nausea malaise hyperactivity
138
Is BSS valuable for chemo or optogenetic manipulations of satiety circuits
Yes it is valuable
139
What are cons of BSS observational analysis
Labour-intensive needs highly skilled observer
140
What is the ideal combination of methods for rich behavioural data including meal pattern analysis and BSS
Pellet dispenser automated scales with observational analysis BSS
141
Where can peripherally injected radiolabelled GLP-1 be detected in the rat brain
Only in the subfornical organ SFO and area postrema AP
142
Why is peripherally injected GLP-1 detected only in SFO and AP
These are parts where the BBB does not function properly
143
What question does the limited detection of peripherally injected GLP-1 raise
If other brain GLP-1 receptors are only reached by GLP-1 released from PPG neurons
144
What does fluorescently labelled liraglutide show regarding binding sites
Shows further binding sites beyond SFO and AP
145
Does systemic liraglutide elicit neuronal activity cFos only in brain areas with GLP-1 receptors
No in many parts of the brain not just those with GLP-1 receptors
146
In which specific brain area do all cells with cFos show presence of GLP-R after systemic liraglutide
Only in the AP
147
What is the anorectic action of GLP-1 producing PreProGlucagon PPG neurons
DREADD chemogenetic activation reduces food intake
148
Does the anorectic effect of PPG neurons appear primary or secondary
It appears primary as BSS is maintained with no indication of nausea
149
Do GLP-1 produced by PPG neurons and GLP-1 agonists act on the same receptors in the same way
Research suggests they might not
150
Did semaglutide and liraglutide decrease food intake independently of PPG neurons in a study
Yes they did
151
What happened when chemogenetically increasing the activation of PPG neurons was combined with semaglutide administration
Food intake was further decreased
152
What does the finding that combining PPG neuron activation and semaglutide further decreased food intake suggest
Combination therapy might be feasible to increase scope or decrease unwanted side-effects
153
What combination drug example is given that suppresses food intake more than either drug alone
Combination of Lorcaserin and Liraglutide
154
What does the differential action suggest about GLP-1RAs entering the brain
They might not be acting on all central GLP-1 receptors in the same way as endogenous central GLP-1
155
What abolishes lorcaserin hypophagia according to a study
PPG-NTS neuron ablation
156
What does PPG-NTS neuron ablation abolishing lorcaserin hypophagia indicate about lorcaserin action
Lorcaserin partially acts via PPG neurons
