Food intake Flashcards
1
Q
why are we becoming obese
A
failure to maintain balance between energy intake and energy expenditure
2
Q
development of an obesogenic environment
A
- rapid environmental change
- rapid behavioural change
- slow evoluationary adaptation to obesogenic environment
3
Q
treatments for obesity
A
surgical (gastric sleeve, bypass and band)
pharmacological (orlistat)
4
Q
how is appetite regulated
A
peripheral signals
5
Q
what internal signals act on the hypothalamus to regualte appetite
A
- hormonal
- metabolic
- neural
6
Q
what hormonal signals act on hypothalamus to regualte appetite
A
leptin, insulin & GI
7
Q
what neural signals act on hypothalamus to regualte appetite
A
gastric distention
8
Q
what metabolic signals act on hypothalamus to regualte appetite
A
glucose, lipid and AA metabolism
9
Q
what do metabolic, hormonal and neural signals act on to regulate appetite
A
hypothalamus
10
Q
how does the environemtn affect appetite?
A
palatabilty of food & adverse food behaviours act on the cortical which signal to hypothalamus
11
Q
hungery & satiety are regualted by the
A
hypothalamus
12
Q
where does the hypothalamus recieve information from on energy status
A
the adipose tissue, becuse it is the major energy depot.
signals travel to the brain via blood stream as endocrine signal
13
Q
how does energy status reach the brain
A
signal travesl from adipose tissue to the brain, as an endocrine signal - via the blood
14
Q
what does the ob gene encode
A
leptin
15
Q
what gene encodes leptin
A
ob
16
Q
ob/ob mouse
A
produces inactive leptin and so continuous feeding occurs leading to obesity, hyperphagia, hyperglycaemia etc
17
Q
what does the db gene encode
A
leptin receptor
18
Q
what gene encodes leptin receptor
A
db
19
Q
db/db mouse
A
produces defective leptin receptor so the hypothalamus does not get signal to reduce feeding = obesity
20
Q
liposatic/adipostatic theory
A
total body weight maintained by regualting fat contetn.
hypothalamus senses [circulating factor] which provides info on size of fat stores
21
Q
what is circulating factor
A
leptin
22
Q
do ob/ob mice have circulating factor?
A
no
23
Q
do db/db mice have circlating factor?
A
yes, but they don’t have the receptor for it and so are unresponsive to it
24
Q
set point hypothesis
A
blood borne factor controls b.weight at a defined set point by interaction with the hypothalamus. depletion f energy stores increases food intake to maintan energy homeostasis
25
is leptin a long or short term signal
long term
26
what type of hormone is leptin
polypeptide hormone
27
where is leptin mainly expressed
adipose tissue
28
circulating levels of leptin are proprtional to
total fat mass
29
when do levels of leptin decrease
after feeding
30
how do leptin levels change
in humans; they will increase after several days with over feeding but rapidly decrease with food restriction
31
could leptin treat obesity?
probably not. Leptin is more responsive to food restriction than it is over-eating. Thought to be a survival trait for starvation
32
how does leptin causes weight loss
- decreases food intake
| - increases energy expenditure via sympathetic innervation
33
what are leptin levels like in the obese
higher than usual (not expected) hence can't be used to treat obesity q
34
when can leptin be effective weight loss treatment?
extremely rare cases where people are leptin deficientbecuase of a defective Ob gene
35
potential way for leptin to be effective
increase the body's sensitivity to leptin
36
what is the leptin receptor
member of the cytokine family
37
where are leptin receptors expressed
mostly in the hypothalamus, also in liver muscle, adipose & other tissues
38
summary of how leptin resistance develops in obesity
- expansion of adipose tissue
- increased leptin secretion
- increased serum [leptin]
-continuous stimulation of leptin receptors
- down regualtion of leptin receptor signalling
= leptin resistance
39
what does falling serum leptin levels signal
tells the brain body is starving
40
what does leptin deficiency drive
hunger & surpasses energy expenditure
41
how does leptin reduce appetite
leptin binds to leptin receptor in the hypothalmus to cause a neuronal signal to the regionof brain that reduces appetite
42
how does leptin increase energy expenditreu
leptin stimulates the hypothalamus which directs signals via the sympathetic neuron to increase thermogenesis in adipose
43
what does increased leptin cause
reduced appetite
| increased energy expenditure
44
what dissipates heat in thermogenesis
UCP-1 uncoupling protein
45
how does UCP-1 work
in thermogenesis, UCP1 dissipates heat by causing heat loss as energy in the proton gradient without energy being stored in reactive moleucles such as ATP
46
leptin binding to leptin receptor causes increased release of
anorexigenic peptides
| POMC and CART
47
leptin binding to leptin receptor causes downregulated release of
orexigenic peptides
| NPY and AGRP
48
orexigenic peptides
NPY and AGRP
49
anorexigenic peptides
POMC and CART
50
POMC and CART are what kind of petides
anorexigenic
51
NPY and AGRP are what kind of peptides
orexigenic
52
when are POMC and CART increased
when leptin binds to leptin receptor
53
when are NPY and AGRP reduced
when leptin binds to leptin receptor
54
what do POMC and CART do
decrease food intake
incease EE via increased sympathetic tone
increase fat oxidation
55
what do NPY and AGRP do
increase food intake
decrease EE via reduced sympathetic tone
decrease fat oxidation
56
hypothalamic peptides that regulate food intake
POMC and CART (anorexigenic)
| NPY and AGRP (orexigenic)
57
POMC is not actually a
peptide
58
ARC
arcuate nucleus
59
PVN
paraventricular nuclues
60
LHA
Lateral hypothalamic area
61
gene that produces anoreixic peptide
POMC
62
1st order signal example
leptin binding to receptor initiaites production of POMC from the ARC nucleus
63
where is POMC produced
ARC nucleus
64
what does POMC produce
alpha-MSH
65
where does alpha MSH come from
POMC
66
what does alpha MSH do
Alpha-MSH binds to MC4 receptor on the PVN to decrease appetite
67
how does POMC decrease appetite
POMC prouces alpha MSH which binds to MC4 receptor on the PVN to decrease apptite
68
how does alpha MSH reduced appetite
binds to MC4 receptor on the PVN to decrease apptite
69
what is coexpressed with POMC in ARC neurons
CART
70
where are POMC and CART coexpressed
ARC
71
what is AGRP
orexigenic peptide that is similar to the agouti protein responsible for yellow hair pigment in mice
72
what is AGRP coexpressed with
NPY
73
where is AGRP expressed
ARC nucuels of the hypothalamus
74
Where is NPY expressed
ARC nucuels of the hypothalamus
75
What is NPY
powerful orexigenic peptide
76
what is NPY co expressed with
AGRP
77
how does NPY work
binds to Y1 receptors on the POMC neuron to prevent anorexigenic action
binds to LHA neurones to stimulate orexigenic action
78
which peptide prevents anorexigenic action and stimulates orexigenic action
NPY
79
where does NPY bind
Y1 receptor on POMC neuron and LHA neurons
80
what are AGRP and NPY inhibited by
high leptin
81
when are POMC and alpha MSH present
high leptin
82
satiey signal
POMC and alpha MSH
83
hunger signal
NPY and AGRP
84
what does leptin mediate
an adipostat feedback loop from fat cells to the brain to suppress appetite and cause peripheral lipolysis and FA oxidation
85
what does a mutated POMC gene cause
hyperphagia
obesity
red hair
86
what does POMC knockout in mice cause
obesity
| impaired pigment
87
what are involved in 2nd order signalling
MCH and orexin = orexigenic
CRH and TRH - anorexigenic
melanocortin receptos
88
how many melancortin receptors are there
4
89
what are the functions of melanocrotin receptors
MC1 skin and hair
MC2 adrenal
MC3 hypothalamus
MC4 hypothalmus
90
which melanocortin receptor controls food intake
MC4
91
agonist of MC4
alpha MSH
92
antagonosit of MC4
AGRP
93
What determines how active MC4R is
balance of alpha MSH (stimulates) and AGRP (inhibits)
94
how does leptin influence MC4
leptin stimulates POMC which produces alpha MSH which stimulates MC4R
95
what does effect does active MC4R have on food intake
reduces food intake
96
MC4R mutations
associated with morbid obesity
97
most common monogenic cause of inherited morbid obesty
MC4R mutations
98
% of morbidly obese children with mutation of one MC4R allele
4%
99
phenotype of MC4R obesity
- hyperphagia starts ~8mnths
- tendency towards tall stature
- hyperinsulinemia
100
effect of agouti on alpha MSH
agouti blocks the action of apha MSH at:
MC1R inhair follicles resulting in yellow pigmentation
MC3R and MC4R in the hypothalamus, resulting in obesisty
101
MCR are blocked by what
agouti like proteins
102
MCR are essentil for the control of
body weight
103
anorexigenic peptides in 2nd order signalling
CRH and TRH
104
orexigenic peptides in 2nd order signalling
MCH and orexin
105
what are CRH and TRH
anorexigenic peptides in 2nd order signalling
106
what are MCH and orexin
orexigenic peptides in 2nd order signalling
107
where is CRH secreted
PVN
108
CRH
corticotropin-releasing hormone
109
TRH
thyrotropin-releasing hormone
110
where is TRH secreted
PVN
111
What does CRH do
acts on the anterior pituiaty to realse ACTH which stimulates cortisol release from adrenal cortex which reduces appeptire
112
what does ACTH stimulate
cortisol release from the adrenal cortex
113
where is cortisol released
adrenal cortex
114
effect of cortisol on appeitte
reduces appetite
115
what is cortisol
stress hormone
116
ACTH
adrenocorticotropic hormone
117
where is ACTH released
anterior pituitary
118
when is TRH down-regualted
fasting
119
how is TRH release stimulated
leptin increases production of alpha MSH which stimulates TRH release
120
what does TRH do
TRH acts on the anterior pituitary to release TSH which stimulates release of TH from the thyroid gland which stimulates metabolic rate
121
what does TRH act on
anterior pituitary
122
where is TSH release from
anterior pituitary
123
what does anterior pituitary release in 2nd order signalling
ACTH and TSH
124
What does TSH stimulate
release of TH from thyroid gland
125
where is TH released
thyroid gland
126
MCH
melanin concentrating hormone
127
where is MCH over expressed
ob/ob mouse hypothalamus
128
when is MCH increased
fasting in both obese and normal
129
Where are orexins produced
exclusively inthe lateral hypothalamic area LHA
130
What does the LHA exclusively produce
orexins A and B
131
what can cause narcolepsy
Orexin deficiency
132
orexin deficieny can cause
narcolepsy
133
why does orexin deficieny cause narcolepsy
possible survival link between energy homeostaisi and wakefullness
