What type of meal produces the greatest release of serotonin within the hypothalamus?
A carbohydrate rich meal
What is the gene that produces leptin
The Ob gene
How come Sibutramine has been withdrawn from clinical use?
It has been linked to cardiovascular side-effects
What can cause the basal metabolic rate to slow down?
- Diet or starvation
- Sustained illness
What are the differences of NAD+ and NADP+ function?
- NAD+ carries electrons during catabolism to Oxygen during respiration
- NADP+ supplies electrons for biosynthetic reduction in anabolic processes
What is Sibutramine a derivative of?
The amphetamine precursor β-phenylethylamine
Where does the Vagus nerve project to regarding information about stomach distention and CCK release?
The nucleus of the solitary tract, which then feeds into the hypothalamus
What class of drug is Sibutramine (Reductil)?
A serotonin and noradrenaline reuptake inhibitor (SNRI) - Antidepressant
What is insulin's effect on the hypothalamus?
It stimulates it to release anorectic peptides such as α-MSH
What are some of the serious complications of obesity?
- Pulmonary disease; obstructive sleep apnoea
- Idiopathic intracranial hypertension
- Coronary heart disease
- Non-alcoholic fatty liver disease
Which layer of the embryo does the GIT develop from?
What are the 3 main nuclei of the hypothalamus involved in appetite regulation?
- Lateral hypothalamic area
- Venteromedial hypothalamic area
- Arcuate nucleus
What are the proteins that are expressed as part of the orexigenic pathway?
- Neuropeptide Y (NPY)
- Agouti-pathway related protein (AgRP)
How much weight is gained with every 3500Kcal excess ingested?
Approximately 1lb of fat
Where is dopamine produced?
The ventral tegmental area and substaintia nigra
What 2 naturally occurring endocannabinoids are mimicked by Delta9 THC (cannabis)?
- 2-arachidonyl glycerol
What are the basic behaviours that the hypothalamus controls?
- Hunger; glucostat cells, leptin receptors
- Thirst; osmoreceptors in OVLT
What are the effects of endocannabinoid activation on the mesolimbic system (Hedonic)?
It increases dopaminergic signalling in the nucleus accumbens
It produces synergism with the opioid system
This also produces the feeling of hunger --> "Munchies"
Which drug, that has now been withdrawn, blocked the CB1 receptor?
Which tissues rely solely on glucose for metabolism?
- Muscle (severe exercise)
What is Orlistat a derivative of?
Lipstatin; produced by Streptomyces toxyricini
Where in the brain does Ghrelin act?
It acts on the arcuate nucleus of the hypothalamus
What tissues use fatty acids as a source of energy?
- Kidney cortex
- Cardiac muscle
- Skeletal muscle (except severe exercise)
What conditions are grouped together in the term "Metabolic Syndrome"?
- Type 2 diabetes
Where do both the orexigenic and anorexigenic pathways feed into in the brain?
The lateral hypothalamus
What 2C molecule is used for ketogenesis?
What is the first line treatment for obesity?
Lifestyle modification; diet and exercise
Which tissues use ketone bodies as a source of energy?
- Cardiac muscle
- Kidney cortex
- Brain in starvation
- Skeletal muscle
What substances in the brain suppress food intake?
- Corticotropin-releasing hormone/ urocortin
- Cocaine and amphetamine regulated transcript (CART)
What enzyme does leptin inhibit in the hypothalamus?
Where is leptin secreted from?
Which nucleus in the hypothalamus senses a decrease in blood glucose and drives the feeling of hunger?
Lateral hypothalamic area
Over what BMI has increased cardiovascular disease mortality and an increased of type 2 diabetes been linked to?
A BMI over 24/25
What are the central neuropeptides and neurotransmitter that stimulate food intake?
- Neuropeptide Y
Where is Ghrelin synthesised?
It is produced from cells in the fundus of the stomach
Which part of the arcuate nucleus is the appetite suppression (anorexigenic pathway) located in?
The dosrolateral part of the arcuate nucleus
How is α-melanocyte-stimulating hormone (α-MSH) produced in the arcuate nucleus?
It is formed by the cleavage of POMC by the action of PC1
How does Orlistat help with weight loss?
It inhibits gastric, pancreatic and carboxylester lipases therefore inhibiting the digestion and absorption of fat through mixed micelles
What is the receptor that α-MSH binds to?
What are the symptoms of Prader-Willi Syndrome?
- Chronic feeling of hunger leading to obesity
- Low muscle tone
- Short stature
- Cognitive disabilities
- Problem behaviours
Which nucleus in the hypothalamus senses a rise in blood glucose after a meal is taken?
Venteromedial hypothalamic area
Where is the appetite stimulating (orexigenic) pathway found in the hypothalamus?
It is found in the venteromedial area of the arcuate nucleus
What hormones are released by the small intestine and pancreas after a meal and have been linked with the feeling of satiety?
How is the Vagus nerve activated following a meal?
- It is activated by stomach distention
- Cholecystokinin also activates the Vagus nerve
Besides α-MSH, what other appetite related protein binds to the Mc4 receptor, and what effect does the binding have?
- AgRP and it inhibits the recepetor, which is the opposite function to α-MSH
Where in the brain does leptin exert it's effect?
The arcuate nucleus of the hypothalamus
What effects does endocannabinoid activation have on the hypothalamic control of hunger?
It enhances the orexigenic pathway through down-regulation of corticotropin-releasing hormone (CRH) and inhibits Mc4 receptor
This all leads to the feeling of hunger --> "Munchies"
What factors can increase the basal metabolic rate?