Rania Mohamed El-Sharkawy

rania.elsharkawy@alex-mri.edu.eg Lecturer of clinical chemistry, MRI-Alexandria

University ,CPHQ,LSSGBHealth governance –MRI-Alex university unit

coordinatorIHI Egypt & NAHQ member

Gut Control of Satiety

What is satiety………

GENERALY……..

•After ingestion of a certain amount of food , suppression of hunger occurs that will lead to termination of food intake this process is referred as `satiation` .the time of satiation is followed by a period of variable duration that is characterized by the absence of hunger , and this is referred as `satiety`.

•Central control of food intake and energy balance

•Peripheral control of food intake and energy balance

The peripheral control is either long term or short term signals

How does satiety happens ………

•Mechano- and chemoreceptors •Gastric peptides

•Nutrients and food intake

Short term regulation of Satiety

•Mechanoreceptors and chemoreceptors signaling as well as the presence of food in the GIT tract contribute to satiety in the postprandial period.

•Nutrients (glucose, aa..) and GIT peptides are also involved in the short term regulation of food intake.

•Short term Peripheral control

How does satiety happens ………

•Short term Peripheral control

How does satiety happens ………

•Short term regulatory mechanisms are insufficient to regulate energy balance and body adiposity •They should act with the long term regulatory mechanisms ( (leptin, insulin, ..) for determination of body adiposity and energy consumed over a period of time.

How does satiety happens ………

GENERAL CONCEPTS

The chemical constituents of food are detected by specialized secretory cells in the gut epithelium releasing satiety mediators many of which act through the stimulation of the vagal afferents

Satiety signals Satiety signals

• Gastric distension

• Gut peptides, hormones, and factors

• Ileal brake mechanism

Satiety signals

• Most come from the GI tract.

• Secreted in response to food ingestion, create a sensation of fullness or satiety.

• Act within the time frame of a single meal

Stomach

factors

Entry of food to the stomach and to the proximal small intestine….

Mechano-and chemoreceptors

•This will lead to stretch of the mechnoreceptors , also gastrointestinal chemoreceptors in response to nutrient products of digestion ( sugars, FA,..) •Signals from these gastrointestinal receptors are transmitted via vagal afferent nerves to the hindbrain where integration of this visceral input occurs and leads to satiety sensation .

Nutrients ingestion stimulates secretion of the blood stream gastrointestinal peptides….

Gastrointestinal peptides

•Most of these peptides causes meal termination and hence called satiety signals.

Produced from gastric mucosa ….

Gastrin-releasing polypeptides and bombesin

• Regulates secretion of gastrin • Peripheral administration inhibits food intake and reduces appetite .

Produced from gastric mucosa ….

Gastrin-releasing polypeptides and bombesin

• Biological actions: • gastrin, CCK, PYY, insulin release , inhibition of food intake, satiety

Intestinal factors

5-hydroxytryptamine (5-HT),

glucagon like peptide-1 (GLP-1),

Intestinal factors……?

Cholecystokinin (CCK),.

polypeptide YY (3-36)

•Released from I cells in the duodenum in response to nutrients particularly fat and protein

•Enters the blood, acts on gut motility, decrease the gastric emptying , gallbladder contraction, gastric and pancreatic enzyme secretion

•CCK8, CCK22, CCK33 : principal circulating forms secreted in response to meal

Cholecystokinin (CCK) - A well-characterized satiety factor

• Diffuses locally to activate CCK-A receptors present on the vagal sensory nerves

• Secreted after food intake → signal transmitted by vagus → stop food intake

Cholecystokinin (CCK) - A well-characterized satiety factor

•CCK stimulate vagus nerve to pancreas (via CCK-A receptor) → release of Ach, GRP, VIP → fusion of granule with membrane and release of pancreatic enzyme

Cholecystokinin (CCK) - A well-characterized satiety factor

CCK action

CCKCCK

gallbladder

Bile

FOOD

+

-

liver

+

fats & peptides

bile & enzymes

fat & protein digestion

- HCl

STEPS OF CONSTRUCTION

Approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the alimentary canal (gut) , where it is used to regulate intestinal movements.

•Inhibit secretion of gastrin, VIP, GIP, secretin, motilin, GH, insulin, glucagon

•↑ fluid absorption and ↓ secretion from intestine•↓ endocrine and exocrine pancreatic secretion•↓ bile flow and gall bladder contraction•↓ gastric acid secretion and motility•↓ absorption of glucose, amino acid, triglyceride

Serotonin (5 hydroxytryptamine)

•It is released in response to ingestion of meals which potentiate glucose-induced insulin release

•GLP-1 is also believed to play an important role as one of the hormones of the “ileal brake mechanism,” an endocrine mechanism that is activated by the presence of nutrients in the ileal lumen and which serves to inhibit gastric motility and secretion

Glucagon like peptide GLP

inhibition of gastric emptying may in itselfcause a limitation of food intake, through either neural or endocrine signaling pathways, perhaps associated with distentionof the stomach

Glucagon like peptide GLP

Action of GLP-1

Amylin and calcitonin gene related peptide

Released from beta cell of the pancreas with insulin, it acts on brain receptors to reduce food intake

Pancreatic polypeptide

•Released from the pancreas in response to food ingestion

•Released in response to vagal stimulation, gastric distention, fat/amino acid/glucose

•It was shown to be reduced in conditions associated with increased food intake

•Action : decrease pancreatic enzyme and HCO3 secretion

Polypeptide YY 3-36

•Released from the L-cells of small intestine

•Peak plasma levels appear postprandially after 1 h

•Circulating levels of PYY are sensitive to nutrient intake

Polypeptide YY 3-36

•Ingestion of nutrients causes L-cells in the gastrointestinal tract to release PYY(1–36), which is an endogenous ligand for several NPY receptors (Y1, Y2, and Y5)

Polypeptide YY 3-36

•However, a cleavage product of PYY(1–36), PYY(3–36), is relatively selective for the NPY Y2 receptor. The NPY Y2 receptor is expressed in the ARH (arcuate nucleus of the hypothamalmous)

Polypeptide YY 3-36

•Circulating PYY(3–36) is thought to suppress appetite through inhibition of ARH NPY neurons

Polypeptide YY 3-36

•↓ vagally mediated gastric acid secretion, gastric emptying

• ↓ pancreatic enzyme and fluid secretion by inhibiting neural pathway to pancreas and ↓ pancreatic blood flow

•↓ intestinal motility, food intake

Increased feeding (orexigenic effect)

• Secreted by oxyntic cell in gastric fundus

• Can be found in pancreas, intestine, hypothalamus, pituitary gland

Ghrelin

Ghrelin

•Food intake•Ghrelin level increases 1-2 hr prior to meal, max just before eating and decreases dramatically within 1 hr after meal•Degree of ghrelin level decrease is in proportion with calories and composition of food (CHO can decrease ghrelin > fat)

Factors influencing it secretion

Increased feeding (orexigenic effect)

•Acting at arcuate nucleus by stimulation of NPY/AGRP neurons (neuropeptide Y/ Agouti-related peptide) →↑ appetite (orexigenic effect)

Ghrelin

•Meal Termination: Long term satiety….

Adipose tissue

over view…..

Adipose tissue signals:Leptin, secreted by fat cellsMalonyl-CoA, blood levels rise during absorptive phase

Meal Termination: Long term satiety….

Leptin …..

Discovered in 1994 by Jeffrey FriedmanCytokine, produced by fat cells, placenta and ?stomachDiurnal variation: peak in nighttimeReceptors (gp130) located in most tissues, with a long form of the receptor in hypothalamus Bigger fat cells produced more leptin Leptin levels correlate with body fat content

Meal Termination: Long term satiety….

Signals from Adipose TissueLeptin:

A hormone secreted by adipose tissue; decreases food intake and increases metabolic rate, primarily by inhibiting Neuropeptide Y (NPY)-secreting neurons in the arcuate nucleus of the hypothalamus

Conclusion….

The long term and the short term regulators for food intake has to be work in synergy for the long term regulation of food intake as well as energy expenditure

Both………