12. Obesity (2) - adipose tissue biology Flashcards Preview

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Flashcards in 12. Obesity (2) - adipose tissue biology Deck (13):

What happens to adipose tissue in obesity? (5)

1. adipocyte growth
- hypertrophy (increased size)
- hyperplasia (increase #)

2. lipoxia - FA spillover into blood

3. decreased adipose blood flow, angiogenesis - hypoxia

4. infiltration by macrophages

5. unregulated production/secretion of adipokines


Why do adipocytes become hypoxic?

tissue expands, vasculature unable to meet oxygen demands
- hypoxic
- leads to inflammation
- recruit macrophages


What causes macrophage infiltration?

Monocyte chemoattractant protein (MCP-1)
- inflammatory cytokine
- produced my adipose tissue during obesity/diabetes
- recruits "monocytes" and other inflammatory cells


What do macrophages do? (3)

1. Angiogenesis - formation of new blood vessels

2.Clearing of necrotic tissue

3. Secretion of inflammatory cytokines

*communicate with adipocytes to influence whole body inflammation and insulin sensitivity


2 phenotypes of adipose macrophages?
- which is prevalent in obesity?

M2 - alternatively activated macrophages
- promote angiogenesis, clear pathogens

M1 - classically activated macrophages
- promote inflammation, extracellular matrix destruction

*shift from M2 to M1 in obesity


Visceral (VAT) vs. Subcutaneous (SAT) fat
- macrophage infiltration

MCP-1 higher in visceral fat
- both lean and obese individuals


Macrophage infiltration change with weight loss

Decrease MCP-1 with weight loss
- exercise and calorie restricted diet

*point: protein is modifiable with lifestyle change


Portal theory
- why does excess visceral adipose tissue lead to insulin resistance?
- problem with theory?

Portal vein carries blood from abdomin to the liver
- VAT drains directly into portal vein
- VAT highly lipolytic
- excess FFAs drain into portal vein and go to liver
- accumulation of FFA in liver increases insulin resistance

- mouse study, SC fat placed in VIS fat depot improves whole insulin sensitivity
- fat types are intrinsically different


Study: transplant visceral or subcutaneous fat from donor mouse to visceral or subcutaneous regions of another


Subcutaneous fat into visceral depot
- improved whole body insulin sensitivity "independent of location"
- mostly adipose, little change in muscle
- suggests that crosstalk exists between SC fat regardless of location
- SC fat has some "cell-autonomous" properties (independent under its own control)


What are the cell-autonomous properties of subcutaneous fat?

differences in
- gene expression
- degree of cell proliferation
- capacity to differentiate
- lipid content
- unknown secreted factors

*little is known about this yet


What is rosiglitazone?

- insulin-sensitizing drug used in diabetes
- PPAR-gamma agonist
- leads to weight gain
- increase "subcutaneous" adipose tissue**
- decrease plasma FFAs
- decrease muscle and liver lipid content


Study: Rosiglitazone on fat distribution and insulin sensitivity
- 7 days


shift adipose tissue to "safe" subcutaneous depots
- improved whole body insulin
- some weight gain



Transcription factor
- increase adipocyte differentiation

(rosiglitazone drug is an agonist to this)