Feeding and Satiety Flashcards
What are the BMI ranges for normal, overweight, obese and morbidly obese?
Normal - up to 25.
Overweight - 25-29.9.
Obese - 30-39.9.
Morbidly obese - >40.
What other conditions can obesity contribute to?
Stroke (hypertension), resp disease (sleep apnoea), heart disease (lipids, diabetes, hypertension), gallbladder disease, osteoarthritis, dementia, NAFLD, diabetes, cancer, hyperuricaemia and gout.
What are 3 functions of fat in our bodies?
Energy storage, prevention of starvation and energy buffer during prolonged illness.
What is the result of the brain re-programming after long-term obesity?
Your brain views the extra weight as normal and dieting as threat to body survival i.e. defends new weight.
What are the 3 ways that the CNS influences energy balance and body weight?
- Behaviour - feeding and physical activity.
- ANS activity - regulates energy expenditure.
- Neuroendocrine system - secretion of hormones.
What is the neural centre responsible for controlling energy intake and body weight?
The hypothalamus.
What are the 3 basic concepts that underlie the hypothalamuses control of body weight?
- Satiety signalling.
- Adiposity negative feedback signalling.
- Food reward.
Define satiation, stiety and adiposity.
Satiation: sensation of fullness generated during a meal.
Satiety: period of time between termination of one meal and the initiation of the next.
Adiposity: state of being obese.
What regulates meal initiation, termination and inter-meal frequency?
Short term processes.
What do satiation signals do during meals and why?
Increase to limit meal size.
List the proteins involved in satiety signals and what effect do they have?
Cholecytokinin (CKK), peptide YY (PYY3-36), glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), obestatin. They make you feel full.
What is the hunger signalling protein called?
Ghrelin.
What type of peptide is ghrelin?
An octanoylated peptide.
Where is ghrelin produced and secreted?
Oxyntic cells in stomach.
What are the functions of ghrelin?
Stimulates food intake (hypothalamus), decreases fat utilisation (helps control fat metabolism, increased lipogenesis in liver and adipose tissue).
What hormones are produced in peripheral tissues to act on hypothalamic neurones to communicate the status of fat stores in the brain?
Leptin (made and released from fat cells) and insulin (made and released from pancreatic cells).
What happens to the levels of leptin and insulin in blood as more fat is stored?
They increase.
What gene mutation caused obesity in mice (mimics starvation, causes unrestrained appetite and obesity)?
Ob/Ob spontaneous mutation (the gene that codes for leptin).
What other gene mutation causes obesity in mice and what other effects did this have?
Having no functional leptin receptor (db/db mutation). Also became hyperglycaemic, hyperinsulinaemic and insulin resistant.
What other gene mutations can cause obesity in humans?
POMC and MC4-R.
Where are there high levels of leptin receptors (Ob-Rb)?
In the hypothalamus.
What effect does intracereberoventricular (ICV) leptin and insulin have on rodents?
Inhibits food intake and decreases body weight.
What are the functions of leptin?
Food intake/energy expenditure/fat deposition, peripheral glucose homeostasis/insulin sensitivity, maintenance of immune system, maintenance of reproductive system, angiogenesis, tumourigenesis, bone formation.
How do the peripheral and hypothalamic actions of insulin differ?
They are opposite (peripheral insulin is anabolic).
What pathways cause the food reward and what else are they implicated in?
Dopamine pathways. Substance abuse and drug addiction.
Why can leptin not be used therapeutically in common obesity?
Most obese individuals have severe leptin resistance.
Why does diet-induced obesity result in leptin resistance?
- Defective leptin transport into brain. 2. Altered signal transduction following leptin binding to its receptor.
What previous anti-obesity drugs have been withdrawn due to side effects?
Noradrenergics, serotonergics, Fen-phen.
What system did rimonabant target and what were the side effects of this drug?
The endocannabinoid system. Severe depression, promotes development of neurodegenerative disease.
What used to be the only drug prescribed to treat obesity?
Orlistat.
What is the mechanism of orlistat and what are the side effects?
Inhibits pancreatic lipase decreasing triglyceride absorption (reduces efficiency of fat absorption).
Side effects: cramping, severe diarrhoea.
Other than the side effects, what are the downsides of orlistat?
You need to take vitamin supplements (fat-soluble vitamins), may not be particularly effective over long term.
Name a drug that is going to be marketed in the UK soon.
Contrave.
Name a new anti-obesity drug coming.
Liraglutide (Saxenda).
What type of drug is liraglutide and how is it taken?
Glucagon-like peptide 1 receptor antagonist. Has to be injected.
What side effects are still to be ruled out with liraglutide?
Thyroid and pancreatic cancer.
What are the benefits of bariatric surgery?
Produces substantial weight loss that is also sustainable, induces high level of complete resolution of type 2 diabetes.
How may bariatric surgery resolve type II diabetes?
Altered secretion of peptides from stomach and gut that affect beta cells and hypothalamus e.g. GLP-1, PYY3-36, ghrelin.
How may brown adipose tissue help with obesity?
Increases energy expenditure by uncoupling of oxidative metabolism from ATP production.
What is the protein in brown adipose tissue that causes the uncoupling?
Uncoupling protein 1 (UCP1).
Can white adipose tissue be changed to brown adipose tissue?
Some can.
What causes more activity of brown adipose tissue and why is this not widely used?
2,4-dinitrophenol (DNP), can kill people due to hyperthermia.
