White adipose tissue Expansion aand Accumulation

Question 1

What determines the mass of adipose tissue?

Answer 1

-Hypertrophy: swelling of existing adipocytes to accommodate excess nutrients such as triglycerides
- Hyperplasia: an increase in adipose stem cell proliferation with subsequent de novo adipogenesis. A fat stem cell becomes an adipocyte

Question 2

Why is it important to know how adipose tissue grows?

Answer 2

Helps differentiate between the types of obesity that a person may have. Pathological or metabolically healthy obesity

Question 3

Pathological obesity:

Answer 3

having more visceral fat instead of subcutaneous fat. Impaired adipogenesis and adipocyte dysfunction This ultimately leads to ectopic lipid deposition and insulin resistance (don’t forget, adipocytes are used in glucose metabolism).

Question 4

Metabolically healthy obesity

Answer 4

has more subcutaneous fat than visceral. It involves having adequate adipogenesis and proper maintenance of adipocyte function

Question 5

How do we make a fat cell (adipocyte)

Answer 5

• We make adipocytes during embryogenesis and adulthood
• Human development: at 14.5 weeks there are no fat cells but at 15 weeks vascular invasion (angiogenesis). Fat cells develop at 20 weeks

Question 6

Why is vascularization a required component?

Answer 6

Provides nutrients(lipids) and oxygen
Provides a scaffold to grow off
Adipose stem cells live along the vasculature which allows them to grow, divide and generate people deposit
Ex: mice aren’t born with fat tissues; they develop it after birth. Their blood vessels are required for adipocyte generation

Question 7

Why should we care about WAT development?

Answer 7

Embryonic changes- developmental patterning and specification
Maternal diet
Maternal obesity
Maternal epigenetic(study of behavior and environment impacts the way your genes) regulation
Resulting in childhood and adult obesity (It’s a huge predictor of adult obesity)

Question 8

Development of WAT

Answer 8

Fat cells are formed and filled through the 2nd and 3rd trimesters. The vasculature is extremely important for fat cell formation
Changes in maternal diet and in-utero exposure to chronic overnutrition can impact the offspring’s adipocyte development

Question 9

Adipogenesis

Answer 9

Makes adipocytes
1st: Adipose-derived stromal cells (ASCs), need a signal to induce adipocytes.
2ndt: Lipid biogenesis makes pre-adipocytes.
3rd: Lipid coalescence and maturation: forms mature adipocyte (one big droplet)

Question 10

Transcriptional Program of adipogenesis

Answer 10

Ppary: Peroxisome Proliferator-Activated Receptor Gamma: Nuclear Hormone receptors: they are transcription factors that bind to DNA and they are Ligand activated
- Necessary and sufficient for adipogenesis (driver of it)
Regulated genes involved in lipid storage and insulin sensitivity

Question 11

TZDs

Answer 11

agonist of PPary. To help with obese people however causes heart attacks, water retention, higher chance of stroke and bone structure

Question 12

Lipid droplet composition and organization

Answer 12

made up of triglyceride, sterol ester, and lipid droplet-associated proteins

Question 13

Lipid Droplet biogenesis:

Answer 13

Step 1: DE NOVO triacylglycerol synthesis with the Er, is made up of fatty acids and glycerol
Step 2: Formation of Oil Lens in the membrane, built up of the lipids within the ER bilayer which forms the oil lens. The ER membrane topography and associated proteins help form a lipid droplet
Step 3: Budding and Nascent Lipid Droplet Formation, fission of ER bilayer from lipid droplet, released into the cellular cytoplasm. Form giant lipid droplets

Question 14

Lipid droplet-associated proteins:

Answer 14

protect droplets and enhance growth. Enhances lipolysis, shuttling lipids, and is involved in expanding lipid droplets

Question 15

Why is Lipid Droplet biogenesis important:

Answer 15

• It’s altered in Obese people
• Obesity induces adipocyte cell death ( they get too big and rupture): releasing lipids into the serum
• Changes in lipid droplet association
• Their size causes them to be dysfunctional and leads to an inability to store fates in adipocytes

Question 16

Adipocyte Expansion and Contraction:

Answer 16

• Adipocyte volume increases with BMI in humans because you’re consuming more lipids that make bigger fat cells.
• Hypertrophy: excess nutrients are converted into triglycerides, creating enlarged adipocytes. Changes the tissue structure and function. Now they are unprotected
  EX: crown-like structures increase (dying adipocyte), the number decreases but the volume increases

Question 17

Adipocyte Hypertrophy Causes:

Answer 17

• Swelling of existing adipocytes to accommodate for the excess nutrients
• Continued overnutrition leads to the dysregulation in lipid droplet biogenesis
• Leads to max lipid size = dysfunctional signals. The signals will recruit immunological cells stimulate fibrosis within the tissue and more dysfunction
• This leads to uncontrolled lipolysis and lipid spillover, removing the lipids that have been stored and releasing them into circulation
• This leads to hypoxia (lack of vascularization), fibrosis(development of fibrosis) and inflammation
  Because of the uncontrolled lipolysis organs like the liver will try to compensate and store the fats to prevent lipo toxicity.

Question 18

Dysfunctional Lipolysis:

Answer 18

• think its in a fast state
• Insulin resistant so glycolysis is happening
• Losing the lipid-associated proteins exposes the lipid droplet to the lipolytic machinery.
• This attacks the droplet and releases fatty acids into the bloodstream ( bad thing)
• Makes the enlarged adipocyte shrink in size when dysfunctional

Question 19

Lipolysis:

Answer 19

Lipolysis is turned on in the fasted state, and releases stored energy to function like epinephrine
Increases cAMP

Question 20

Lipolysis Steps:

Answer 20

• cAMP phosphorylates hormone-sensitive lipase (HSL, an enzyme)
• HSL cleaves the triglycerides into free fatty acids
• Free fatty acids are released into the blood and is utilized for energy

Question 21

Insulin block lipolysis:

Answer 21

• Insulin tells the fat cell to stop converting triglycerides to free fatty acids and use glucose for energy instead. Store the excess as triglycerides
• This doesn’t happen in the obese state because fat cells are enlarged and desensitized to insulin mediates signaling

Question 22

Hyperlipidemia

Answer 22

increased blood fats