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Obesity (Body Mass Index (BMI) (BMI = mass (kg)/height (m)^2, BMI<18.5…

- - - - burn energy at
        cellular level
        
        interefe with mitochondrial function
      - exercise
    - - food intake
        
        determined by
        
        hedonic factors
        
        pleasure from eating
        
        homeoistatic factors
        
        need of eating to survive
      - Lorcaserin
        
        5HT2CR antagonist - stimulates satiety
    - - interfere with gut epithelium to
        decrease the absorption of nutrients
      - Orlistat
        
        blocks lipases, enzymes digesting lipids
        into absorbable form from the GI tract
      - consume non-nutritious food
    - - Sibutramine
        
        stimulates B3 adrenoceptors on adipose tissue promoting lipolysis (fat burning)
  - - - connecting alimentary
        limb to mid-jejunum
    - - reducing the stomach size
- - - - 5HT
        
        5HT2cRs in the brainstem
      - NA
        
        acting on A1 and B adrenoceptors in the hypothalamus
      - melanocortins
        (from POMC)
        
        alpha-MSH
        
        decrease food intake
        
        increase food expenditure
        
        act on MC3 and MC4 receptors
        
        synthesised in Arcuate Nucleus neurons
        which project to other hypothalamic areas
    - - NPY
        
        lowers energy expenditure
        
        increases lipogenesis
        
        synthesised in Arcuate Nucleus neurons,
        which project to the paraventricular nucleus
        
        inhibited by Insulin and Leptin in a negative feedback loop
      - orexin
      - AgRP
        
        melanocortin (POMC) release inhibitor
        
        lowers energy expenditure
        
        no effect on food intake
      - endocannabinoids
        
        anadamide
        
        act on CB1 receptors in the hypothalamus
      - Dopamine
        
        food as a reward
        
        antagonism of D1 and D2 receptors reduces food intake - probably by removing the dopaminergic reward component
  - - - adiposity
        
        Adiponectin
        
        Insulin
        
        inhibits NPY synthesis
        
        increases POMC synthesis
        
        Leptin
        
        stimulates POMC melanocortin release
        
        inhibits NPY release in hypothalamus
        
        stimulates GLP-1 in brainstem
        
        Produced by adipose tissue --> increasing fat
        stores increases leptin production
        
        ob/ob mice - lack leptin gene
        
        db/db mice lack leptin receptor gene
      - satiety signals
        
        GLP-1
        
        incretin
        
        released from endocrine gut cells
        
        reduces blood glucose level
        
        PYY
        
        decreases food intake
        
        CCK
        
        meal termination signal
        
        increases 5HT release in the hypothalamus
        
        acts on CCKb receptors which are key satiety mediators
        
        gastric distension
        
        Glucocorticoids
        
        endogenous leptin/insulin antagonists
    - - hunger signals
        
        Ghrelin
        
        In normal people levels decrease after eating
        
        not in obese people
        
        Secreted by the stomach
        
        release regulated by leptin
        
        inhibits 5HT release