Lecture 19: Hypothalamus - feeding and drinking Flashcards
What is the lipostatic hypothesis? What was concluded from this?
Your body is always trying to keep a certain weight. In rats, it was observed that after a period of starvation the rat would lose weight, but when fed normally the rat weight would increase to what it was before: the “set point.”’ This also occurred when overfed, the rat would gain weight but the period of forced feeding stop the rat would lose weight until it returned to the “set point.” Therefore it was thought that there was some kind of circulating factor communicating weight to the brain.
Which experiment confirmed a hormonal factor in the blood determined body weight? Which hormone was later confirmed to control appetite and energy expenditure?
Parabiosis experiments by Coleman with genetically obese mice (ob/ob mice). Normal mice were joined together with ob/ob mice so that they shared the same blood supply. It was found that the obese mouse lost weight when sharing blood supply with the normal mouse. Therefore it was confirmed that there was a hormone in the blood communicating weight to the brain Leptin was later discovered as the hormone that controls this
What is leptin? What is leptin deficiency?
- a blood borne factor released by adipocytes (fat cells) proportionally to the amount of fat there is in the body.
- when you gained weight, the leptin levels would increase – signaling the brain to eat less
- found that additional leptin reduced appetite when given to normal mice and increased energy expenditure of the mice as well.
- suggested that leptin prevented us from starving to death (if leptin decreases - we eat more)
Leptin deficiency
Is a cause of obesity in small number of individuals - when someone is leptin deficient the brain thinks that they have no body fat - therefore increasing appetite and decreasing energy expenditure
couldn’t be used as treatment for obesity unless the person had mutation in leptin. Leptin treatment in these individuals change feeding behaviours and energy expenditure to normalise weight.
Describe an experiment that confirmed leptin resistance.
When a diabetic overweight (db) mouse was fused with a normal mouse - the normal mouse lost weight. The db mouse had extremely elevated levels of leptin which crossed over to the normal mouse resulting in starvation. The db mouse has deficient leptin receptors in the hypothalamus resulting in no response to elevated leptin levels.
When an ob mouse and a db mouse were fused together the ob mouse lost weight due to the leptin being replaced.
What happens when the lateral hypothalamus is lesioned or damaged?
Damage to the lateral hypothalamus causes anorexia via a severely decreased appetite for food.
What happens when the ventromedial hypothalamus is lesioned or damaged?
It causes obesity and over-eating.
What is the dual centre hypothesis?
It was the idea that the ventromedial hypothalamus was the satiety centre, and that the lateral hypothalmus was the hunger centre. It was thought that they worked in opposition with eachother. This hypothesis was based on hypothalamic lesions whereby:
- Lesions in the lateral hypothalamus resulted in severely reduced appetite and anorexia
- Lesions in the ventromedial hypothalamus caused overeating and obesity.
BUT this hypothesis is overly simplistic
What happens in the hypothalamus with an increase in leptin levels?
- Elevated leptin levels activate alpha-MSH and CART neurons of the arcuate nucleus in the hypothalamus.
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alpha-MSH and CART neurons project to
- and activates the paraventricular nucleus
- which coordinates the endocrine response - the increased secretion of thyroid stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH)
- direct axonal projections from the paraventricular nucleus projext to brain stem neurons and preganglionic neurons of the sympathetic ANS.
- the intermediolateral gray matter of the spinal cord (activate brain stem neurons and preganglionic neurons of the ANS directly)
- inhibit feeding behaviour via projections to the lateral hypothalamus (somatic motor response)
- and activates the paraventricular nucleus
What happens when you inject alpha-MSH and CART into the brain?
It mimics the brains response to elevated leptin levels - they act as appetite suppressants
What happens if you inject a drug that blocks alpha-MSH and CART?
It would increase feeding behaviour as these peptides normally suppress appetite
What happens in the hypothalamus when there are decreased levels of leptin?
Decreased leptin levels activate NPY and AgRP neurons in the arcuate nucleus - they then cause the opposite effects of alpha-MSH and CART neurons.
- NPY/AgRP projections to the paraventricular nucleus inhibit the secretion of hypophysiotropic hormones (corticotropic releasing hormone and thyroid releasing hormone) controlling ACTH and TSH, consequently decreasing cortisol and T3 and T4 levels. Decreased T3 and T4 results in a drop in the basal metabolic rate and decreased cortisol results in a decrease in gluconeogensis in the liver and decrease carbohydrate metabolism.
- NPY/AgRP projections to the lateral hypothalamus activate melanin-concentrating hormone and orexin neurons causing increased feeding behaviours
What are MC4 receptors?
The MC4 receptor is found on the lateral hypothalamus and its activation inhibits feeding. AgRP and alpha-MSH are antagonistic and act on this same receptor
- alpha-MSH is a agonist
- AgRP is an antagonist - blocking the receptors and stimulating feeding
What drives feeding behaviours in the lateral hypothalamus?
antagonism of the MC4 receptor by AgRP neurons reslts in activation of orexin and melanin concentrating hormone neurons as well as acitvation of neurons in the medial forebrain bundle.
- MCH and orexin neurons have wide projection targets that go throughout the brainstem and cortex - that result in food seeking behaviours.
- Orexin neurons projec tot the preoptic area and are more related to arousal and wakefulness - it may increase arousal to find food.
What regulates feeding behaviour in the short term?
Arexonogenic signal from the periphery: Ghrelin is released from the stomach when empy - it acts on NPY and AgRP neurons to drive feeding behaviour.
Why does gastric banding surgery work?
It reduces the amount of ghrelin released from the stomach, resulting in a decrease in the drive to eat.
