MD140 (Hormonal Appetite Regulation)

Hormones that the pancreas produces (3)

1. Amylin 2. Glucagon 3. Insulin

Hormones that the small intestine produces (3)

1. CCK (Duodenum) 2. GLP1 (Ileum) 3. PYY3-36 (Ileum)

Clinical applications for ghrelin

1. GH defiency 2. Eating disorder - Anorixia / Bulimia nervosa 3. GI disease 4. Cardiovascular disease 5. Osteoporosis 6. Aging 7. Catabolic state / chronic wasting syndrome eg AIDS

Hormones that the colon produces (2)

1. GLP1 2. PYY3-36

Hormones that the stomach produces (2)

1. Ghrelin 2. Leptin

Ghrelin activity (6 steps)

1. Ghrelin binds to GHSR on arceus nucleus neurons 2. GHSR activates its G-protein, which in turns activates its phosphlipase (PLC) 3. PLC turns PIP2 into IP3. 4. IP3 binds to its receptor and stimulates sER to release Ca2+ into the ICF. 5. Increased Ca2+ levels increases the firing rate of NPY / AgRP-producing primary neurons, so more NPY / AgRP is produced. 6. The same primary neurons also release GABA, which inhibits POMC-producing neurons. Therefore overall, orexigenic neurons are more active than anorexigenic neurons.

Short-term hormonal control of appetite (4)

1. Ghrelin: Released from empty stomach - Orexigenic signals - Stimulates NPY / AgRP-producing primary neurons - Ghrelin secretion stops after food intake 2. PYY3-36: Released from intestinal endocrine cells - Anorexigenic signals - Inhibits NPY / AgRP-producing primary neurons - Similar structure to NPY 3. CCK: Released from proximal small intestine - Anorexigenic signals - Causes early phase satiety - Mediate pre-absorptive satiating effect of intestinal fat infusions, which regulates fat intake 4. GLP-1: Incretin hormone released from the gut after food (particularly carbohydrate) intake - Anorexigenic signals

Long-term hormonal control of appetite (3)

1. Insulin: Released from pancreatic islet cells after carbohydrate or protein intake - Anorexigenic signals - Inhibits NPY / AgRP-producing primary neurons - Stimulates POMC-releasing primary neurons 2. Leptin: Released from adipose tissue - Anorexigenic signals - Inhibits NPY / AgRP-producing primary neurons - Leptin release increases with both body fat and insulin levels 3. Amylin: Secreted alongside insulin from β-cells of Islets of Langerhans. - Anorexigenic signals - Works with insuline to suppress glucagon secretion and slow gastric emptying - Reduces hunger, controls body weight

Hormone secretion by entero-endocrine cells (4 steps)

1. Nutrient is sensed by taste bud-like receptors 2. Causes rise in ICF Ca2+ concentration 3. This triggers exocytosis of neurotransmitters and satiation peptides from the receptors 4A. Satiation peptides diffuse across ECF to enter circulation and interact with afferent vagal nerves 4B. Neurotransmitters synapse with nerve fibres leading back to hindbrain to trigger more satiety responses

Signals that induce satiety hormone secretion by entero-endocrine cells (2)

1. Nutrient uptake and metabolism 2. Activation of taste receptors

Entero-endocrine taste receptors - Descrption (3)

1. Similar to taste bud cells 2. Coupled to G-proteins 3. Causes rise in ICF Ca2+ concentration

Sites where hormone receptors are located (2) Hormone's kind of effect on appetite

1. Vagus afferent nerves 2. Arcuate nucleus neoron cell surfaces Hormones have modulatory effect on appetite, and act in concert (additive effect) to control food intake

Types of Primary Neurons (2)

1st type: Stimulate appetite by secreting neuropeptides (NPY and AgRP) 2nd type: Depress appetite by secreting POMC

Appetite control

Appetite is controlled by the arcuate nucleus in the hypothalamus. It is co-ordinated with the body's energy utilization. Food intake (based on appetite) is thus adjusted according to physical activity, to maintain body weight. The arcuate nucleus measures metabolites and hormone levels, then co-ordinates metabolism by adjusting the activities of liver / kidneys / intestines / adipose tissue.

Factors that affect Ghrelin levels (3)

Ghrelin levels... 1. Rise during starvation / empty stomach 2. Fall after food intake (aka postprandilly) 3. Are low in obese people, high in lean people

Entero-endocrine cells - Location, function

Location: Scattered between enterocytes on the villi within small intestinal wall Function: 1. Sense nutrients and non-nutrients (other molecules) in food 2. Release satiation peptides. These peptides can also enter bloodstream to act as hormones. 3. Satiation peptides affect vagal-afferent fibres, hindbrain hunger centre, arcuate nuclear neurons accordingly. 4. Through this, they mediate macronutrient-specific neural activation.

Long-term vs Short-term hormonal control of appetite

Long term: Controls arcuate nucleus neurons Short term: Controls hindbrain hunger centres and arcuate nucleus

Ghrelin activity (not secretion) is dependent on...

Octanoylation (modification) by GOAT in rER of ghrelin-secreting cells. It's needed to permit ghrelin binding to GHSR.

Orexigenic vs Anorexigenic signals

Orexigenic: Increase appetite Anorexigenic: Cause satiety (decrease appetite)

Primary vs Secondary Neurons in the arcuate nucleus

Primary (aka orexigenic): Sense metabolite levels and regulating hormones Secondary (aka anorexigenic): Synchronize information from primary neurons and co-ordinate bodily functions through vagal signalling