SUZANNES SVAR PÅ TENTAMENSFRÅGORNA
NR 14 OCH NR 26!


Förfärligt adipös kissekatt!!!... Nu får den obesa kissen medicin!!!... Nu har kissen blivit smal och fin!!!




Hej alla studenter,

- Suzanne ville ge här ge er rätt svar till frågorna 14 och 26 på tentamen för Delkurs 4:



Question 14:

What role do NPY neurons have in the control of energy balance?

They increase food intake (and may also have effects to reduce energy expenditure).


Can you provide any experimental evidence for this?

Either:
1. Infusion of NPY into the brain of normal rats for one week causes a dramatic increase in food intake, such that the rats already have a large increase in body fat (and hence body weight).

2. Scientists expected NPY knockout mice to eat less and have a lean phenotype as NPY is a potent orexigenic peptide. However, this turned out not to be the case – they had normal food intake and normal body weight, probably because other important body weight-regulating systems compensated for the loss of NPY during development.

3. If there are good NPY antagonists available then it may be possible to show reduced food intake and reduced body weight in animals treated with such a compound.

4. NPY mRNA expression is elevated in the brains of diet-induced obese rats (as increased fat results in increased circulating leptin levels that increase NPY mRNA expression in the arcuate nucleus of the hypothalamus).

You are Pharmacy students! Use your imagination!
This is not a study about parabiosis (that show the existence of circulating (blood-borne) satity factors that act in the brain. It is also not a question about lesion. If you lesion the medial satiety centres of the brain where the NPY neurons are located then you also lesion the anorexigenic POMC neurons too. What will be the outcome and how would that give you any specific information about NPY as an orexigenic peptide?



Question 26:

Currently there are 3 anti-obesity drugs available in Europe and another one available in the US. For at least 2 of these drug, comment on how effective they are for weight loss and describe what is known about their mechanism of action.


Xenecal
This drug reduces intestinal fat absorption by about one third. Obese patients treated with Xenecal may expect to lose around 10% body weight in one year but often regain weight after they stop taking the drug. Mechanism: It binds to gastrointestinal lipases preventing triglyceride breakdown, a necessary first step for fat absorption. Additionally, the side effect steatorrhoea (fat in stools) can cause anal leakage and discomfort causing the obese subjects to eat less fat in the first place.


Sibutramine
This drug is a serotoninergic and noradrenergic reuptake inhibitor. Obese patients can expect to lose less than 10% body weight when treated with this drug for one year but often regain weight once they stop taking the drug. Mechanism. By increasing serotonin levels in the brain, this drug increases satiety. By increasing noradrenaline levels in the blood, it increases activity of the sympathetic nervous system. Side effect is raised blood pressure.


Exenatide
This is a new drug approved recently in the US. This drug mimics the action of the intestinal hormone GLP-1, that is normally release after food intake. It acts in the brain to reduce food intake and thereby reduce body weight. Other effects include reducing gastric empying (which may prolong the feeling of fullness) and increase insulin sensitivity (which improves the diabetic status of many obese individuals). Weight loss is modest in obese patients but the additional beneficial effects on insulin sensitivity with no unwanted side effects make this a rather popular drug for obesity currently.


Rimonanbant
This drug has just recently been approved for use in obese patients in Europe. It is an antagonist at the CB1 receptor (cannabinoid 1 receptor). This receptor is expressed in many tissues, notably in the reward systems of the brain that is associated with pleasure and incentive behaviour. It was tested originally for nicotine addiction when it emerged to suppress appetite. Rimonabant is currently the most effective drug available for weight loss. When treated for one year with this drug over 44% of patients lost more then 10% body weight.



Hälsningar

Joakim
kursledare

(2006-11-07)