block 6- aging and disease Flashcards
(44 cards)
what is sedentary behaviour?
periods of low energy expenditure(sitting, watching TV, reading, video games, sleeping…)
How does having a sedentary lifestyle(physical inactivity) contribute to death worldwide
Sitting time is correlated with higher mortality rate Watching TV 6h/day → 2x higher mortality rate compared <2h/day Sedentary lifestyle: 30% higher mortality rate when engaged in high physical activity compared to low physical activity Park JH et al. (2020) from non-communicable diseases attributed to physical inactivity associated with 1 in 6 deaths in UKSeDS: sedentary death.
-Nearly 1 in 3 adults worldwide, at risk of disease from lack of physical activity in 2022
adaptive thermogenesis
-process by which the body adjusts heat (energy) production in response to environmental and physiological factors such as:
-Cold exposure
-Overfeeding or underfeeding
it helps maintain energy balance and body temperature.
Regulation:
Controlled by the hypothalamus, which receives:
Signals from blood nutrient levels
-Leptin from white adipose tissue (fat cells
controlled by hypothalamus (signals from blood nutrients and leptin from white adipocytes)
how is energy utilized in the body?
50% obiligatory energy expenditure = required for cellular and organ function
. 25%physical activity= dependents on the amount you do
-25% adaptive thermogenesis
the role of leptin in human physiology-CHEAT SHEET
-Leptin is a hormone produced mainly by white adipose tissue.
It signals the hypothalamus to regulate:
Appetite suppression
-Energy expenditure
-Body weight homeostasis
Leptin Receptors:
Leptin acts via leptin receptors (ObRs), primarily in the hypothalamus.
Multiple receptor variants exist (Ob-Ra to Ob-Rf):
Example: Ob-Re circulates in blood and binds leptin, helping buffer its activity.
Leptin & Obesity:
Homozygous ob/ob mutations (complete leptin deficiency) are extremely rare in humans but cause severe early-onset obesity.
Most obese individuals have high leptin levels, not low.
This suggests leptin resistance — the body stops responding to leptin signals effectively.
As a result, appetite remains high and energy expenditure doesn’t increase, despite high leptin
How does lepin work?
-Leptin is produced principally by white adipocytes
Leptin binds to the Ob-Rb receptor (the main signaling form of the leptin receptor) in the hypothalamus.
This activates the JAK/STAT signaling pathway.
The effects include:
↓ Food intake (appetite suppression)
↑ Energy expenditure, partly via adaptive thermogenesis
Downstream Effects:
Behavioral changes (e.g., reduced hunger)
Neuroendocrine responses (e.g., effects on thyroid and reproductive hormones)
Autonomic nervous system activation (mainly via the sympathetic branch), promoting:
Heat production in brown adipose tissue
Increased metabolism
why is leptin not a solution for obesisty?
✅ In Normal Physiology:
More fat = more leptin.
Leptin signals the hypothalamus to:
Reduce appetite
Increase energy expenditure
When body fat decreases (e.g. from dieting):
Leptin levels fall
This tells the brain to increase hunger and reduce metabolism, making it harder to maintain weight loss.
⚠️ In Obesity:
Obese individuals already have high leptin levels (due to more white adipose tissue).
However, they often develop leptin resistance:
Leptin can’t cross the blood-brain barrier effectively
There’s impaired leptin receptor (Ob-Rb) signaling in the hypothalamus
Result: The brain doesn’t ‘see’ the high leptin, so appetite remains high and metabolism stays low — similar to someone who is starving.
what the original causes of obesity?
-many reason e.g. overeatting,low energy expenditure and physical inactivity
metabolic dysfunctions due to physical inactivity- DONT THINK ITS TOO IMPORTANT SKIP
- see slide for full details
-skeletal muscle: reduced fatty acid oxidation,glucose uptake and muscle mass
adipose tissue: increase in adipose mass,cell volume and free fatty acids
how is obesisty explained by evolution?
we are no longer hunting for food and have limited food accesses and so. the hunters before us was on the borderline between food intake : energy expenditure(just enough food to support daily energy expenditure. but we have now evolved into gathers and so dont need any energy to get food
-we also tend to evole the mindset of saving energy when given the option e.g. taking lifts instaed of stairs
blood glucose concentrations in diabetes
- in the diabetes block!!!!
regulation of glucose
-pancreas detects glucose in the blood
-B cells in islet of langerhan = increase insulin induces glucose and uptake and storage
-muscle= coverys to glycogen
-adipose tissue = conversion to triglycerides
-liver= conversion to glycogen, inhibits gluconeogeneisis
Type 1 diabetes
- autoimmune disease which destroys B cells=no insulin
-insulin injection needed
type 2 diabetes
- β-cells of Islets of Langerhans still produce insulin* Insulin resistance
type 2 disabetes
- β-cells of Islets of Langerhans still produce insulin* Insulin resistance
what happens to insulin receptors when there is insulin
When insulin binds to its receptor, it activates a signaling pathway that causes:
Rapid insertion of GLUT-4 transporters into the cell membrane (mainly in muscle and fat cells)
This increases glucose uptake from the blood
How does type 2 diabetes disrupt insulin receptor signaling-CHEAT SHEET
↑ Adipose tissue mass → ↑ Free fatty acids (FFAs) in circulation
FFAs and other factors inhibit insulin signaling, particularly the PI3K pathway
This reduces GLUT-4 insertion into the cell membrane, lowering glucose uptake
Also impairs triglyceride storage and increases inflammatory signaling
📝 Note: These changes weaken insulin’s effects, causing high blood glucose despite high insulin levels.
when can insulin resistance be beneficial?
- during seasonal fat storage in hibernating animals =keeps them warm as they rely on their fat storage only
what is the role of microbiota in insulin resistance in hibernating animals and humans
-The gut microbiome has a powerful role in regulating metabolism.
-Healthy microbiota (like those producing butyrate) protect against insulin resistance.
-Dysbiosis (Unhealthy Microbiota):
Caused by high-fat diet and ↑ Gram-negative bacteria
Leads to:
↑ LPS (bacterial toxin) in the blood → Endotoxemia
Increased intestinal permeability
Chronic inflammation
↓ Butyrate → reduced metabolic protection
🧠 Result:
→ Impaired insulin signaling
→ Progression of type 2 diabetes
reversing insulin resistance
- loosing weight which has many benefits
-such as dcrease Free FFA - if damaged too severe can not be reversed
atheroclerosis
Atherosclerosis is a disease where fatty deposits (plaques) build up inside the arteries, making them narrow and stiff. This can reduce blood flow and lead to heart attacks, strokes, or other problems.
what are the steps leading to atherosclerosis plague rapture- IGNORING CURRENTLY
Plaque rupture happens when the fibrous cap over a build-up of fat and immune cells in the artery wall becomes too thin and weak, leading to rupture and potentially a heart attack.
🧠 Key steps:
LDL-C (low-density lipoprotein cholesterol) enters the endothelium and gets oxidized (OxLDL).
Monocytes enter and become macrophages, which absorb OxLDL and turn into foam cells.
Foam cells and smooth muscle cells (SMCs) form a fatty plaque in the artery wall.
SMCs normally produce collagen and elastin to form a fibrous cap.
🧱 Plaque types:
Stable plaque:
Thick fibrous cap
Small necrotic core
Low risk of rupture
Vulnerable plaque:
Thin fibrous cap
Large necrotic core
High risk of rupture
🔥 Why rupture happens:
Macrophages release enzymes (metalloproteinases) that break down collagen, weakening the cap.
The necrotic core grows, and the cap thins → rupture due to pressure.
🧨 Cap rupture exposes inner contents to the blood, triggering blood clotting (thrombosis) → can block artery → heart attack or stroke
what are the mechanism aloowing regular exercise to reduce chronic disease development?-NOT LEARNING RN CHEAT SHEET
-Metabolic adaptations in trained muscle:
↑ Muscle mass and insulin sensitivity
↑ Ability to use lipids (fat) as energy
↓ Conversion of glucose into fat
↓ Circulating triglycerides and ↓ fat storage
Systemic benefits:
Improved physical fitness enhances general health
Strengthens immune response → improved resilience against disease and infection
Anti-inflammatory effects:
↑ Anti-inflammatory exerkines released during exercise
→ Counteract the low-grade inflammation linked to chronic diseases (e.g., cardiovascular disease, diabetes, cancer)
Specific anti-tumour effects via myokines:
Myokines released from active muscle (e.g., IL-6, oncostatins, irisin, SPARC) have direct anti-cancer actions
Epidemiological evidence:
→ Exercise reduces risk of at least 13 cancer types
→ Improves survival in prostate, colorectal, and breast cancer
Stress response activation (acute effect of exercise):
Activates the HPA axis (hypothalamus-pituitary-adrenal)
Activates sympathetic ANS and immune system
Promotes “training effect” → better physiological preparedness for future stress (including disease)
exerkines and myokines
a type of exerkine is myokine released from active skeletal muscle fibres
-can be hormones,metabolites,protein etc… by different organ system e.g.g nervous or cardiovascular in response to exercise
-found in an experiment
-can have many effects e,g, endocrine,autocrine on multiple organ systems
