1. Microenviornment Model
Candy

2. Lean Microenvironment
Key:
Candy equivalent for model:
Adipocyte
Mini marshmallows
Licorice wheel
Blood vessel
Mini Reese’s Dark
Macrophage (M2)
cMET
Life Savers Gummies
Gummy Bears
HGF
T-cells
Skittles

3. Obese Microenvironment
Key:
Candy equivalent for model:
Adipocyte
Large
Marshmallows
Licorice wheel
Blood vessel
Mini Reese’s original
Macrophage (M1)
cMET
Life Savers Gummies
Gummy Bears
HGF
T-cells
Skittles

4. Lean Microenvironment Obese Microenvironment

6. Good vs. Evil Macrophages (white blood cells)
Macrophages can be good or bad depending on the tissue. In lean tissue they are good and are anti-inflammatory. In obesity, they are bad and pro-inflammatory.
(take like 40 sec)
Anti-inflammatory
LEAN Adipose
Pro-inflammatory
OBESE Adipose
Johnson, Immunologic Reviews 2012

7. HGF = “Ligand” protein that sends the message
You can see that the protein called HGF is the ligand. Like a baseball you throw. The receptor is called cMET and like a mitt will catch the signal. This is how one cell talks to another. (take like 10 sec)
cMet = “Receptor”
- Protein that catches the message

8. What does this signal do to cause cancer??
HGF
cMET
ECM remodeling
Growth
Motility
Angiogenesis
Anti-apoptosis
HGF
Do you see how one cell signals to another with protein? That signal (HGF) will tell the mitt (cMET) what to do – all of these things cause cancer.
(take like 20 sec)
Sundaram, S., Makowski, L., et. al. BCRT 142 (3):

9. Lean Adipose Obese Adipose GOOD CELLS BAD CELLS M2 macrophage
Spend time on this. Tissue is made up of a bunch of different cells. In lean or skinny people, These are adipocytes. These are blood vessels. There are GOOD cells involved in making tissue healthy. When you get obese- what happens to fat cells- get bigger, and BAD cells move in to cause trouble. In obesity, these bad cells cause diabetes. Pay attention, in lean we have good white cells called macrophages that are M2 . In obesity, we have bad macrophages that are M1. next slide…
(take like 1 min?)
GOOD CELLS
BAD CELLS
M2 macrophage
Eosinophil
Treg (FOXP3+)
M1 Macrophage
Monocyte
Mast cell
Th1 T cell
Adipocyte
Dying Adipocyte
CD8+ T cell
NK cell
Neutrophil
Basophil
B cell
Th2 T cell
Johnson, Immunologic Reviews 2012