Obesity And Inflammation Flashcards
What is inflammation?
A physiological response to restore homeostasis and repair tissue altered by some insult.
What is acute inflammation?
- short lasting inflammation
- involves influx of proteins, fluid and cells from local blood vessels 🩸 into the damaged area to mediate local defences
What are the local defences that acute inflammation mediates in response to local trauma?
🔪 removal and killing of infective agents 🦠
🗑️ breakdown and removal of the damaged tissues
Give an example of an acute inflammatory response?
Sore throat 🤢
Burn 🔥
Insect bites 🐝
In some cases ,acute inflammation will turn into chronic inflammation, what is chronic inflammation?
Long lasting inflammation 🕰️ it involves an established or an excessive inflammatory response.
What is low grade chronic inflammation?
A persistent mild level of inflammation in the body that can contribute to various health problems over time.
Often will occur without causing any noticeable symptoms.
What is CRP and why is it useful to assess its levels in people in clinic?
It is a biomarker made in the liver.
It is produced in response to inflammation and so if there is >er CRP levels = inflammation present. 🥵
Describe how the CRP levels in a patient with low grade chronic inflammation will appear over time?
They will steadily increase over time
What is the definition of obesity 🧈
A BMI >30
What are the two main risk factors for obesity?
- excessive energy consumption (ie eating lots of fatty food).
- reduced physical activity ( 🛌)
why are the current trends relating to obesity concerning?
Because obesity is increasing in old and young populations → child hood obesity is a growing concern.
What is one of the underlying causes for childhood obesity?
Chronic low grade inflammation - where lots of different cells are releasing cytokines, adipokines and reactive oxygen species
Is obesity associated with genetics?
There are a few genes associated with obesity and BMI however -> they dont account for very much.
Most cases of obesity are due to what types of factors?
Genetic and ** environmental** factors
- ie food consumption, lifestyle etc.
What is ** epigenetics ? **
These are **“gene - environment” ** interactions that lead to heritable changes in the gene expression via DNA modifications.
Modifications to gene expression are often influenced by environmental factors, lifestyle, and experiences thus impacting how genes are turned on and off
Eg of epigenetics : What is the “Dutch winter baby hypothesis”?
- suggests that the maternal nutrition 🤰 🦴 (which as very poor) during winter (Netherlands WW2) may have influenced the foetal genome 👶 where DNA modifications lead to changes in increased risk of metabolic diseases (ie diabetes, obesity) in adulthood. 🤢 🧈
What is epigenetics?
These are gene 🧬- environment 🥘 🌳 interaction that will lead to DNA modifications that lead to heritable changes in gene expression.
Give two examples of genetic modifications that can alter gene expression as a result of epigenetics?
DNA modification - DNA modification that will often lead to gene silencing and reduced gene expression.
** Histone modifications ** - can lead to repression or activation of gene transcription
How does DNA modification affect gene expression?
- will lead to gene silencing 🤫, or reduced gene expression ⬇️
How does ** histone modification ** lead to altered gene expression?
- ➕ activation or repression ➖ of transcription (ie increase or decrease protein synthesis)
What are Long Non Coding RNAs?
✅ They are epigenetic regulators.
The act as scaffolds for the assembly of RNA transcripts and proteins.
❌ they do NOT code for proteins.
How are Long Non - Coding RNAs implicated in obesity?
✅ They regulate adipogenesis , ie the formation of fat cells AND adipose tissue function.
- they thus influence the expression of genes involved in metabolism, energy balance which contributes to the development and maintenance of obesity.
What is metabolic syndrome?
A cluster of biochemical and physiological abnormalities associated with the development of CVD and T2DM.
What are some risk factors for metabolic syndromes?
Major risk factors
✅ obesity (unhealthy diet, sedentary)
☑️ HTN
☑️ Insulin resistance / hyperinsulinaemia
Genetics 🧬 and aging 👵 also play a role.
🦴 what is osteoarthritis?
This is a degenerative joint disease where the tissue in a joint will breakdown over time - “wear and tear”.
- ✅ most common form of arthritis and most common in the elderly.
Describe the link between obesity and osteoarthritis?
Obesity => risk of developing OA
- most patients undergoing joint replacement surgery due to OA are overweight.
What are the two main joints needed to support the body?
- ✅ hip joint
- ✅ knee joint
What are the pathological features of osteoarthritis?
❌ loss of cartilage 🦴
🚇 narrowing of the space in the joints
🦴 changes to subchondral bone
🥵 joint inflammation
😥 pain and reduced mobility - think wear and tear
What is central adiposity?
It is a risk factor for OA and it concerns the waist : hip circumference (WHR)>
What does having a high WHR indicate?
🍎 apple shape body —> high risk for OA
What does having a LOW WHR indicate?
🍐 low risk for OA and metabolic disease
What are adipokines and what do they regulate?
The are pro - inflammatory cytokines secreted by adipose tissue.
✅ They regulate metabolism, inflammation and appetite.
What are the effects of adipokines in the joint?
- ❌ loss of bone cartilage
- 🦴 bone remodelling.
(Synovial inflammation)
How does obesity increase the risk of OA (discuss all risk factors)?
- ✅ 💪 obesity -> hyperplased adipocyteswhich thus will release a lot of adipokines in the serum and synovial fluid ——-> this will lead to ✅ increased bone remodelling and a ✅ reduced cartilage volume
- 🩸 Obesity also leads to -increased inflammatory / immune cell infiltration - ie greater extent of inflammation in the synovial joints.
- 🧫 Obesity also makes the synoviocytes more ** proliferative** —> they thus secrete a greater amount of pro - inflammatory cytokines and will express a >er amount of pro - inflammatory genes
Where else can adipokines have effects (other than the joints) after being secreted from the hyperplased adipocyte cells.
- 💀 skeletal muscle
- 🫀the heart
- 🍺 the liver
- 🩸 pancrease
What is the Central adiposity Obesity Phenotype ?
- ✅ this is when the patients have high waist circumference measurement - such patients often present with additional cardiovascular AND T2DM risk factors?
What are some of the risk factors seen patients with a high central adiposity ?
What is “Inflammaging” ?
The increased expression of inflammatory cytokines IL - 6 and TNF alphaseen in older patients with a higher BMI.
Give two examples of inflammatory cytokines?
✅ IL - 6
✅ INF - alpha
What is sarcopenia? 💪
Age related loss of muscle mass, strength and power and performance.
It is associated with the age - related increase in central adiposity.
In a healthy body its ideal to keep muscle mass ____ and adipose tissue ___________.
- up
- down
How does the ratio of adipose tissue and muscle mass change over time (ie how does it differ from a young person vs old person)?
- young - muscle mass»» adipose tissue
- old - adipose tissue»_space;> muscle mass.
What keeps a fine balance between adipose tissue and muscle mass?
Diet and excercise
How does obesity lead to glucose resistance?
- 🙅♀️ It can lead to the accumulation of triglycerides within skeletal muscle —> inhibition of insulin stimulated glucose uptake
- excessive fat accumulation in the adipose tissue can result in the release of inflammatory signals and adipokines —> such factors will interfere with insulin signalling pathways which will affect the ability of cells to respond to insulin thus imparting insulin action
What does GLUT4 expression look like in skeletal muscle tissue in a person with obesity.
- reduced - thus poor glucose uptake - insulin resistance.
- isolated myotube -in obese ppl are intrinsically insulin resistant and will not respond to insulin —-> thus such ppl have a higher blood glucose level.
How does obesity lead to skeletal muscle atrophy ?
Myoblasts (ie muscle cells) in obese ppl may undergo alterations in signalling pathways, and gene expression ———> thus may influence myoblasts differentiationand so they form thinner myotubules
Give one example of an adipokines that is significantly increased in ppl with a BMI of >25?
✅ resistin.
Give an example of a medication that has been licensed to treat obesity?
✅ Locaserin —-> a selective serotonin 2C receptor agonist.
