302 Gut hormones and Obesity Flashcards
In what ways does obesity harm health?
-Heart disease
-Stroke
-Cancer
-Liver disease
-Reproductive complications
-Depression and anxiety
-Asthma
-Type 2 diabetes
-Osteoarthritis
-Back pain
-Sleep apnoea
What within the body plays a role in metabolic adaptation?
-Decreased energy expenditure
-Thyroid hormones
-Testosterone
-Cortisol
-Gut hormones
-Leptin
What is the function of gut hormones?
-Key regulators of bodyweight
-Act on homeostatic and hedonic brain circuits to modify eating behaviour
What is the function of hedonic pathways?
Related to pleasant sensations
-They’re cortical brain areas that process external sensory info like reward cognition and executive functions
They interact with homeostatic signals to regulate body weight influenced by environmental conditions
Which types of cells sense nutrients?
EEC
Enteroendocrine cells
-They release gut hormones as autocrine, paracrine, and endocrine regulators
Where are EC (enterochromaffin) cells found?
In the stomach, small and large intestine
Where are L cells found?
In the distal small intestine and colon
Where are K cells found?
In the proximal small intestine
Where are I cells found?
In the proximal small intestine
Where are D cells found?
In the stomach (gastric corpus and antrum), and small intestine
Where are G cells found?
In the stomach (antrum) and duodenum
Where are A (X-like) cells found?
Mainly in the stomach
Which gut hormones do L cells respond to?
GLP-1
GLP-2
PYY5-HT
Which gut hormones do EC cells respond to?
5-HT
Which gut hormones do K cells respond to?
GIP
5-HT
Which gut hormones do I cells respond to?
CCK
5-HT
Which gut hormones do D cells respond to?
Somatostatin
Which gut hormones do G cells respond to?
Gastrin
Which gut hormones do A (X-like) cells respond to?
Ghrelin
Name some appetite supressing (anorexigenic) substances in the gut
-Peptide YY 36 (PYY)
-Glucagon-like peptide 1(GLP-1)
-Oxyntomodulin (OXM)
-Cholecystokinin (CCK)
-Glucose-dependent insulinotropic polypeptide (GIP)
-Bile acids
-Neurostatin
-Uroguanylin
-Gastric leptin
-Amylin
-FGF19
Name some appetite inducing (orexigenic) substances in the gut
Ghrelin
What is the function of the Arcuate nucleus?
A part of the hypothalamus that integrates circulating signals of hunger and satiety reflecting energy stores and nutrient availability
-‘Accelerator’ neurones produce NPY that stimulate feeding and blocks neuronal melanocortin receptors by producing agouti-related peptide (AgRP)
-‘Brake’ neurones produce melanocortin peptides that inhibit eating
What is NPY?
Neuropeptide Y
It stimulates food intake
Which long term regulators are released proportionate to the fat storage of the body?
Insulin and Leptin
They have sustained inhibitory effects of food intake while increasing energy expenditure
What is the function of short term regulators of food intake?
They mark the onset and termination of eating
What is the function of ghrelin?
It stimulates appetite by activating NPY/AgRP expressing neurones
It rises quickly when stomach is empty and fall rapidly when food is consumed
What is the function of Cholecystokinin?
It’s released during eating to promote the sense of fullness that encourages an end to the meal
What is the function of PYY (Neuropeptide Y)?
It decreases food intake by inhibiting gut motility
It’s released before nutrients arrive in the lower small intestine and the colon. Further release is stimulated by nutrients within the lower small intestine and the colon
It remains high in the blood before meals and has more central effects
What is the function of Glucagon-like peptide-1 (GLP-1)?
It stimulates insulin secretion and inhibits glucagon secretion
Where is GLP-1 produced?
In EEC-L cells and certain neurones within the nucleus of the solitary tract in the brainstem
What are incretins?
A type of gut hormones
They regulate how much insulin is secreted after eating
What is the function of DPP-4 enzymes?
It inactivates incretins
What are GLP-1 receptor agonists for?
Medications used to treat diabetes T2 and obesity
What effects do GLP-1 receptor agonists have on the pancreas?
Pancreas
-Increased beta-cell function
-Increased insulin biosynthesis
-Increased glucose-dependent glucagon secretion
-Decreased glucose-dependent glucagon secretion
What are the effects of GLP-1 receptor agonists have on the heart?
-Decreased cardiovascular risk
-Decreased fatty acid metabolism
-Increased cardiac function
-Decreased systolic blood pressure
-Decreased inflammation
What is the function of leptin?
It contributes to the felling of fullness
It has effect son the central hypothalamus and peripheral tissues
Where is leptin secreted?
Mainly in white adipose tissue
It’s levels are correlated with the amount of body fat
What happens to different levels of gut hormones during a very low energy diet?
There is increased hunger and increased desire to eat
-Significant reduction in PYY , cholecystokinin (CKK), insulin, leptin, and amylin levels
-Increase in Ghrelin, GIP, and pancreatic polypeptide
What effect does exercise have on levels of gut hormones?
Increased circuiting PYY
Supressed appetite and ghrelin
What is the effect of obesity on the body?
-Dysregulation of energy homeostatic signals
-Consistent overriding of homeostatic signals of energy availability leads to disjointed eating and energy requirements
– Causes dysregulation of the metabolic mechanisms controlling energy homeostasis including secretion of gut hormones
-Leptin resistance in common
What are some psychological co-morbidities of obesity?
Mood disorder 15.6%
Anxiety 24%
Binge eating 16.3%
Avoidant personality disorder 17%
Substance misuse
Night eating syndrome
Body image disturbance
Childhood maltreatment
What is night eating syndrome?
When you eat a lot after dinner, have trouble sleeping, and eat when you wake up at nigh
What is the staging tool for obesity?
EOSS
Edmonton Obesity Staging System
Name some medications associated with weight gain
Risperidone
Lithium
Quetiapine
Aripiprazole
Olanzapine
Valproic acid
Citalopram
Duloxetine
Venlafaxine
Zopiclone
Trazadone
Zoplidem
Pregablin
Gabapentin
Steroids
Insulin
Name some anti-obesity agents
CNS stimulants like Phentermin/Topiramate
Phentermine
Lorcaserin
Benzamphetamine
Bupropion/Naltrexone
Orilstat
Others: metoformin, zonisamide, amuylin agonists, SGLT2 inhibitors
What effects does GLP-1 receptor agonists have on the brain?
Decreased body weight
Decreased food intake
Increased satiety
What effects do GLP-1 receptor agonists have on the stomach?
Decreased gastric emptying
What effect do GLP-1 receptor agonists have on the liver?
Decreased endogenous glucose production
Increased hepatic insulin sensitivity
Increased hepatic insulin sensitivity
Decreased de novo lipogenesis
Decreased steatosis
What is steatosis?
Fatty liver disease
Who qualifies for weight loss surgery?
Patients with BMI above 40
BMI 35-39.9 and a severe obesity related comorbidity Eg. diabetes
What are the 4 common bariatric procedures?
LAGB
-Laparoscopic Adjustable Gastric Banding
-An adjustable band at the top of stomach
Sleeve gastrectomy
-Removing a large part of the stomach
BPD-DS
-Biliopancreatic diversion with duodenal switch
-Removing a lot of the stomach and then bypassing that majority the the intestine
-(Less common)
Roux-en-Y
-Only the top part of stomach remains and is attached directly to intestine
What is the mechanism of weight loss after surgery?
-Increases in satiety promote hormones
-Reduction in hunger promoting hormones
-Reduced food intake
-Central effects
-Altered bile acid metabolism
-Altered intestinal microbiota
What is the hind gut hypothesis?
That diabetes control results from the expedited delivery of nutrient chyme to the distal intestine, enhancing a physiologic signal that improves glucose metabolism
GLP-1 is the main contributor
What do GIP levels correlate with?
The length of intestine exposed to ingested nutrients
How does GIP stabilise glucose levels?
It enhances glucose-stimulates insulin secretion and promotes the secretion of glucagon when glucose is low
What is the outcome of obesity surgery on diabetes?
Diabetes remission after 2 years but relapse at 10 years
