mpb 333 the molecular endocrinology of obesity and diabetes satiety and hunger
TRANSCRIPT
Terminology
HungerFood Seeking Behavior
Meal InitiationMeal
Meal terminationSatietySatiateNausea
Inter-meal IntervalReward
Satiety Signals
• Most come from the GI tract.
• Secreted in response to food ingestion, create a sensation of fullness or satiety.
• Reduce meal size without causing malaise.
• Act within the time frame of a single meal
• Interact with other controllers of meal size.
Satiety Signals
• Reduce meal size comparably– In lean animals and– In genetically obese animals– In diet-induced obese animals
• Blocking their action leads to increased meal size.
• But…body weight not effected after repeated injections.
Forebrain
Hindbrain
The effects of CCK and stomachstretch are integrated in vagal afferent fibers
CCK Stretch
Nodose GanglionVagus
DOSE
30-Minute Food Intake
Cholecystokinin (CCK) - A well-characterized Cholecystokinin (CCK) - A well-characterized satiety factor acting on the NTSsatiety factor acting on the NTS
Released from I cells in the duodenum in response to nutrients particularly fat and protein
Enters the blood, acts on gut motility, gallbladder contraction, and gastric and pancreatic enzyme secretion
Diffuses locally to activate CCK-A receptors present on the vagal snsory nerves
Reduces food intake in the short-term
PYY: a Gut Peptide Released in Response to Short Chain Fatty Acids
Cherbut et al., Short-chain fatty acids modify motility through nerves and polypeptide YY release. Am. J. Physiol. 275, G1415-G1422, 1998
Ilial Infusion50mM SCFA
PYY3-36 Inhibits Food Intake in
Vagotomized Mice
Effect of Vagotomy on PYY3-36action
2 4 6 80
1
2
3Sham Saline n=12Sham PYY n=13
BSDV Saline n=6BSDV PYY n=6
**
Time (h)
Control: Vagotomy blocks inhibition of food
intake by CCK
Ghrelin: a meal initiation factor
acting at the GHS-R
From: Cummings, D.E. et al.Diabetes 50, 1714-1719, 2001
Leptin Tonically Regulates a Multitude of Circuits Involved in Acute Intake and
Expenditure
Behavioral
Endocrine
Autonomic
Synergy by CCK and Leptin to Inhibit Food IntakeMatson and Ritter. AJP. 45:R1038-45, 1999.
Saline CCK Leptin CCK + Leptin
10
0
20
30
40
48-hourchowIntake
(g)
b
a
MC4-R impacts autonomic, endocrine, and behavioral effector pathways to balance energy intake and expenditure so as to maintain energy homeostasis.
The melanocortin system is an ideal neuroanatomical substrate for the integration of long-term and short-term energy needs – a second pathway for tonic effects of leptin on satiety