PHS 3342 Lecture Notes - Lecture 18: Knockout Mouse, Leptin Receptor, Neuropeptide Y
28 Apr 2018
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April 10, 2018
Regulation of Appetite
Regulation of Appetite
No magic drug yet for control of food intake - appetite regulation is complex and we don’t have all the answers yet
-6 peptides/proteins associated with appetite regulation/weight management
Neuropeptide Y
Neuropeptide Y: hypothalamic peptide (arcuate nucleus) that stimulates food intake (primarily carbohydrate) and
decreases metabolism
-Shown to stimulate eating behaviour when injected into brain
Mice study results:
-Mice lacking both leptin and NPY are less obsess than mice lacking only leptin (but still fatter than controls)
-NPY secretion can be reduced by leptin
-But:
•NPY knockout mice exhibited normal food intake and body weight, became gluttonous after being deprived of
food and, when treated with leptin, decreased food intake and lost weight
-Compensatory mechanism proposed
•NPY widely distributed in CNS and implicated in other functions, including mood modulation, cerebrocortical
excitability, cardiovascular physiology
Melanocortins
Melanocortins: group of pituitary peptides produced from POMC that include ACTH and various forms of MSH that
have been shown to decrease appetite; source is also arcuate nucleus
Mice study results:
-Targeted disruption of melanocortin-4 receptor in mice —> obesity
-Administration of melanocortin agonists can inhibit feeding
-Yellow obese mouse produce agouti protein, which antagonizes binding of melanocortins to melanocortin-4
receptor —> these mice become obese
Leptin
Leptin (long-term regulation): protein coded by obesity (ob) gene in adipose tissue that provides feedback on overall
nutritional status of the body (not necessarily right after a single meal)
-Provides feedback to accurate nucleus of hypothalamus where it acts as a satiety factor
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Document Summary
No magic drug yet for control of food intake - appetite regulation is complex and we don"t have all the answers yet. 6 peptides/proteins associated with appetite regulation/weight management. Neuropeptide y: hypothalamic peptide (arcuate nucleus) that stimulates food intake (primarily carbohydrate) and decreases metabolism. Shown to stimulate eating behaviour when injected into brain. Mice lacking both leptin and npy are less obsess than mice lacking only leptin (but still fatter than controls) Npy secretion can be reduced by leptin. But: npy knockout mice exhibited normal food intake and body weight, became gluttonous after being deprived of food and, when treated with leptin, decreased food intake and lost weight. Compensatory mechanism proposed: npy widely distributed in cns and implicated in other functions, including mood modulation, cerebrocortical excitability, cardiovascular physiology. Melanocortins: group of pituitary peptides produced from pomc that include acth and various forms of msh that have been shown to decrease appetite; source is also arcuate nucleus.
