weight regulation hormones Flashcards

Targeting the complex peripheral and central signals involved in weight regulation

• duodenum
• jejunum

cck a

cck b

plasma levels rise within 15 min

1. reduce food intake and in response to meal initiation
2. local regulatory
3. stimulation of gallbladder contraction
4. inhibition of gastric emptying

• reduce food intake (meal size and duration)
• increases in meal frequency
• development of tolerance
• short half-life of the peptide
• hold minimal promise as a future antiobesity tool

stomach

• Binds to the growth hormone secretagogue receptor (GHSR)
• in the hypothalamus and brain stem
• Signaling mechanisms (ARC) and (NPY)/ (AgRP)
  expressing neurons

• Obese >fasting ghrelin levels lower following diet-induced weight loss
• obese > post-prandial fall in circulating ghrelin levels

• induce appetite
• increase food intake

• pre-prandial receptor blockade
• NPY and AgRP antagonists

• endocrine pancreas
• colon
• rectum

• hypothalamic arcute nucleus (ARC) > Y4 receptors
• increase endogenous PP production
• avoiding degradation in the circulation,
• increase Y4-mediated signaling

• low > during the fasting
• rise > in proportion to caloric intake

• reduction in appetite
• reduction food intake

L-cells of the GI tract

• Y family of G protein-coupled receptor
• preferentiality for the Y2 receptor

• influenced by meal composition and calorie content
• elevated within 1 h post-feeding
• often lower in the obese state

• Inhibition of food intake > selective Y2 agonist
• attenuation of this inhibitory effect > Y2 antagonists
• IV PYY3-36 > decrease in appetite and 30% restriction in caloric intake

small intestinal and colonic L-cells

GLP 1 R

• delays in the post-prandial release
• reduced circulating levels of the peptide

• anorexigenic effects
• influences on food intake
• reduction in gastric emptying
• suppression of gastric acid secretion
• GLP-1 or GLP-1 receptor agonists > satiety, reduce food intake, weight loss

• inactivation and clearance by (DPP-IV)
• short half-life of GLP-1 > 5 min

intestinal L cells

GLP 1 R

• increases satiation and reduces food intake
• decreases in body weight
• increased energy expenditure

white adipose tissue adipocytes

• proportional to fat mass
• increased circulating leptin levels
• lack of leptinmediated effects
• leptin resistance > Receptor overstimulation > negative feedback loops > block leptin signaling

• inhibit the orexigenic NPY/AgRP
• stimulate the anorexigenic POMC
• within the hypothalamic arcuate nucleus

• reduce food intake
• reduce body weight
• increase energy expenditure

• central effects on food intake and energy homeostasis are less efficient
• insulin > stimulate the synthesis and secretion of
  leptin > through a feedback loop (adipoinsular axis)
• Common hypothalamic targets
• crosstalk between the two hormones

• proportional to the degree of adiposity

• meals are initiated > non-homeostatic influences
• meal termination > satiation signals
• The efficacy of satiation signals varies with the amount of fat in the body as signaled to the brain by leptin and insulin

1. leptin and insulin secretion both decline
2. reduced adiposity signal reaches the arcuate nucleus
3. lowers sensitivity to satiation signals
4. more food is eaten during meals before satiation

1. have elevated levels of adiposity signals
2. enhanced sensitivity to satiation signals
3. reducing the trajectory of weight gain or even promoting weight loss
4. low doses of leptin or insulin are infused directly into the brain near the arcuate nucleus
5. enhance satiation signals to reduce food intake