Feeding Behaviour Flashcards
1
Q
BMI
A
- BMI=weight (kg)/height (m)
- 600million clinically obese
- 1.9 billion overweight adults globally (26%)
- 62% of Canadians overweight or obese
- continuing BMI increase is being observed in many countries and all age groups
- BMI not perfect indication
- abdominal fat thickness better indicator
2
Q
Obesity causes and consequences
A
- lifestyle
- reduced physical activity
- choice of high fat foods
- quitting tobacco smoking
- use of drugs (cannabis)
- diseases
- Cushings
- growth hormone deficiency
- hypothyroidism
- psychiatric disorders
- cohens
- genes
- polymorphism and mutations of genes involved in energy homeostasis
- consequences
- increase BP, high cholesterol
- diabetes
- non-alcoholic fatty liver
- CV disease
- strokes/cancers etc
3
Q
Energy on request
A
- brain constitutes 2% of body mass but uses 50% of body glucose
- brain burns average of 100g of glucose per day
- discrepancy between brain energy needs and rest body energy needs require precise balancing mechanisms
- these can be disrupted by disorders or stress
4
Q
Central control of feeding
A
- AArcuate nucleus (ARC) in hypothalamus controls feeding
- ARC contains neuropeptide Y (NPY/AgRP) which activate feeding
- ARC also contains POMC neurons which reduce feeding
- inhibitory hormones are leptin and insulin, which stimulate POMC and inhibit NPY/AgRP signalling
- activation of neurons in PVH reduce food intake
- activation of lateral hypothalamic area/perfornical area stimulate food intake
- neurons from all structure project to nucleus tractus solitary (NTS in hindbrain
-obesity is a disruption of neuronal and neuro-hormonal regulation of energy balance and accumulation of adipose tissue
5
Q
Hunger-satiety signalling molecules
A
Inhibitory
- POMC/MSH
- serotonin
- histamine
- leptin
- insulin
- CCK
- Stimulatory
- NPY
- orexins
- endocannabinoids
- ghrelin
- GIP
6
Q
Central factors in feeding
A
- POMC/melanocortin neurons are inhibitory
- AgRP and NPY stimulate feeding
7
Q
Peripheral factors in feeding
A
- inhibitory
- CCK and PYY are acute peripheral signals (released on demand)
- leptin and insulin are chronic inhibitory peripheral factors (reflect long term nutrition state)
- stimulatory
- ghrelin is an acute peripheral factor
-PYY and ghrelin also synthesized by some neurons in brain
8
Q
Melanocortin
A
Agonists increase energy expenditure as measured by indirect calorimeters
-antagonists induce opposite effects
9
Q
Adipose tissue
A
- build up supports inflammation
- high fat diet and obesity induces activation of pro-inflammatory mediators
- counteracts satiety signalling in hypothalamus
10
Q
Maintaining energy balance
A
- thermogenesis
- shivering
- non shivering (brown fat)
- heat is mostly produced in mitochondria by uncoupling proteins
- mitochondrial ATP metabolism and thermogenesis
- fatty acids and glucose oxidized to generate NADH and FADH2 which donate to ETC
- energy from electrochemical gradient of protons can be involved in ATP synthesis or leaks as heat by action of UCP
-mice lacking UCP1 are not hyperphagic and obese byt are extremely sensitive to cold
11
Q
Brown adipocytes
A
- white adipose tissue is responsible for energy storage
- brown adipose tissue involved in energy spending
- BAT contain small lipid granules
- high conc of mitochondria (give brown colour)
- high density of UCPs
- non shivering thermogenesis
- innervated by adrenergic sympathetic neurons (B3 neurons)
- WAT contain single fat droplets that constitute that majority of cell volume
12
Q
B3 knockout mice
A
- survive prolonged cold by compensation mechanisms
- increased shivering
- increase B1 adrenergic signalling
- B3 adrenergic agonist inhibits weight gain in rodents kept on high fat diet
13
Q
WAT can become BAT
A
- transdifferentiation of WAT into BAT was shown in rodents exposed to prolonged cold (6 degrees for 10 days)
- not observed in B3 knockout mice
- B3 agonist induced white adipose differentiation
- indicated that differentiation process depends on B3 adrenoreceptor activation
14
Q
Corticosteroids and obesity
A
-HPA axis and regulation of feeding controlled within hypothalamus
- cortisol availability is dependent on activity of 11B-hydroxysteroid dehydrogenase (11B-HSD)
- 11BHSD1 isoform converts inactive cortisone to cortisol
- 11BHSD2 isoform converts cortisol to cortisone
- cortisone induces adipose cell differentiation
15
Q
Cushing’s syndrome
A
- pathological hypercortisolemia
- associated with obesity, glucose intolerance, hypertension
- adrenalectomy in cushings patients reverses glucose intolerance and obesity
- genetically obese mice demonstrate hypercorticosteronemia
- adrenalectomy in rodents reduces food intake and can be reverse by glucocorticoids
16
Q
Addison’s disease
A
- hypoactivity of adrenal cortex
- associated with low body weight and hypotension
17
Q
Low birth weight and obesity - HPA axis
A
- blood cortisol levels are reversely proportional to birth weight
- antenatal betamethasone (steroid) increases insulin resistance
- in rodents, administration of dexamethasone or inhibition of 11BHSD2 increases fetal glucocorticoid load
- results in diabetes in offspring
- blood cortisol levels increase naturally in late pregnancy and glucocorticoids are require to induce lung maturation
- low birth weight can be associated with increased risk of type 2 diabetes and dyslipidemia and hypertension
18
Q
Link between anxiety and feeding
A
- anorectic peptides (inhibit feeding) —> anxiogenic factors (increase anxiety)
- orexigenic peptides (stimulate feeding) —> anxiolytics factors (decrease anxiety
19
Q
Central inhibitory melanocortins
A
- melanocortins
- a POMC derived agonist of MC1-5 receptors
- mice lacking POMC or MC4-R are hyperpagic (excessive hunger), obese, hyperglycemic, hyperinsulinemia
- 6 week treatment with intranasal a-MSH4-10 in healthy volunteers reduced body fat by 1.68kg
- MC3-R knockouts have increased adipocity but normal body weight
- AgRP is an antagonist of melanocortin receptors
20
Q
Stimulatory NPY
A
- discovered as a peptide inducing vasoconstriction
- highest density of NPY neurons in PVN in hypothalamus
- high levels found in post mortem in CSF of anorexic patients
- repeated stress and high-fat/carb diet stimulate release of NPY in rat hypothalamus
- NPY receptor subtypes Y1 and Y5 stimulate feeding
- Y2 and Y4 inhibit appetite
- PYY and PP act on same Y receptors
21
Q
Inhibitory leptin
A
- primarily produced in WAT but some in other tissues
- possible mutation in mouse LEP gene
- ob/ob obese moulds shows nonsense mutation in codon 105 resulting in a sense of leptin production
- mutation causes obesity, hyperphagia, hypothermia, extreme insulin resistance, infertility
- administration of leptin resorts wild-type phenotype
- db/db mouse (lacks leptin receptor) also obese
- Some human mutations within LEP gene also associated with hyperphagia and obesity
22
Q
Cytokines
A
- some act as anorectic mediators
- adipose produces adipocytokines that may influence energy balance
- adiponectin-deficient mice develope insulin resistance, glucose intolerance, dylipidemia etc
- central injection of adiponectin in rats increases energy loss and decreases fat mass without affecting food intake
- adiponectin associated with energy expenditure and to protect against insulin resistance
23
Q
Cytokines continued
A
- resistin
- peptide produced by adipocytes that increase insulin resistance
- serum levels of resistin are increased in obesity
- Tumor necrosis factor-a serum conc is correlated with amount of body fat
- TFNa inhibits feeding, increases metabolic rate, and induces cachexia (los of body mass that cannot be revered nutritionally)
- possible that TNFa helps trigger weight loss
- IL-6 administered intracerebrally increases energy expenditure
- CSF IL6 negatively correlated with fat mass
- IL6 knock out mice develop obesity in adulthood
24
Q
Stimulatory ghrelin
A
- gastrointestinal hormone
- stimulates growth hormone release
- called growth hormone secretagogue receptor (GHS-R)
- arcuate nucleus in hypothalamus has highest density of GHS-R
- gremlin stimulated food intake but also dopamine release
- induces locomotor activity
25
Ghrelin knockouts
- ghrelin injected significantly increases food intake in wild type mice
- ghrelin doesnt increase food intake in mice with knockout of growth hormone secretagogue receptor (Ghsr-/-)
-ghrelin doesnt increase food intake in mice lacking AgRP and NPY
26
Nesfatin-1
- elevated in some neurological and psychiatric disorders
- patients with newly diagnosed epilepsy have hundreds-fold higher nesfatin1
- normalized after epilepsy treatment
- patients with major depressive disorder have elevated plasma nesfatin1
- plasma nefatin1 also correlated positively with Hamilton depression rating scale in depressed patients and healthy controls
27
Sleep deprivation augments obesity
- sleep deprivation
- decreases leptin
- increases ghrelin
- increases hunger
- chronic HPA axis dysregulation can cause changes in feeding behaviour
- possible increase of sugar to sustain brain during active state
28
Inhibitory PYY
- synthesized by L cells of gastrointestinal tract
- blood PYY dependent on volume and kind of food
- dietary fat is most potent releases of PYY
- 2 endogenous PYYs:
- PYY1-36 (long)
- PYY3-36 (short)
- in fasting, PYY1-36 predominated
- after meal PYY3-36 is height
- both bind to same Y receptor
- PYY3-36 binds to Y2R receptors which are most dense in hypothalamic arcuate nucleus
- knockout is insensitive to exogenous PYY anorexic effect
29
PYY effects
- rats injects with PYY3-36 or agonist of Y2A in PVN or ARC
| - PYY3-36 injected mice significantly reduced caloric intake\
30
Serotonin
- inhibits food intake
- serotonin transporter over-expressing mice are lighter and shorter than wild type
- serotonin transporter knockout mice develop obesity (no hyperphagia)
- mice lacking serotonin receptors exhibit hyperphagia and obesity
31
Histamine
- reduces food intake
- H1 knockout mice develop age related obesity/hyperphagia
- disruption of sleep/wake cycle (especially orexin)
- administration of H3 antagonist surprises food intake
- H1 receptor agonist decrease food intake
- histamine increases expression of UCP mRNA in adipose (increase energy expenditure)
32
Orexins and obesity
- orexin A and B
- orexinergic neurons act as sensor for nutritional status of body
- glucose, ghrelin, AgRP most important mediators for orexin neurons
- adminitration of anti-orexin antibody or OX1R selective antagonist reduced food intake
- mice lacking orexin neurons ate less than control wild type
- OX2R selective agonists suppresses food intake in mice on high-fat diet
- orexin knockouts show cataplexy, fragmented sleep-wake cycles
33
Obesity treatment
- most effective treatment is bariatric surgery
- Orlistat is most common medication (inhibit pancreatic lipase)
- liraglutide
34
Muscles
-skeletal muscles produce and secrete myokines (involved in adipose tissue build up)
35
Beneficial effects of runnning
- runners has 30% lower risk of death from CVD and artery disease
- 45% lower risk of death from heart disease or stroke
- lived bag 3 years longer
- people who ran for less that an hour a week benefited as much as those running more than three hours a week
36
HSP70 and obesity
- hot tub bath (6 days/week for 21 day reduces blood glucose levels and induces weight loss in diabetes patients
- possibly due to increased HSP7
37
Water preloading
-decreases caloric intake
38
Bacteria and obesity
- mice receiving the obese twin microbiota showed increase in adiposity
- those receiving lean twin microbiota remained lean
- mice inoculated with obese microbiota were co-housed with mice with lean microbiota
- lean bacteria invaded obese infected animals preventing weight gain
