Metabolic Syndrome

Lecture 2
Pine Manor College

Pamela Harvey
Objectives

1. Understand the role of insulin in
maintaining proper blood sugar levels
2. Identify basic functions of adipose tissue
3. Understand how inflammation in adipose
tissue begins
4. Describe two cytokines that are released
from adipose tissue and what the effects
are
Metabolic Syndrome
Coronary Artery Disease
&
Diabetes
Insulin Resistance +
Hyperinsulinemia
Increased BMI
Increased central
adiposity

Dysregulation of Blood Glucose

2. Where does it go?
3. What regulates its movement?
1. What is the source of the glucose?
Glucose
What if the insulin system fails?
Too little insulin
Too much insulin
How Does Abdominal Obesity Cause
Insulin Resistance
Central Obesity
Adipose Tissue

Adipose tissue = connective tissue made up of adipocytes
Adipose tissue expands by hypertrophy and hyperplasia
Adipocyte
Blood vessel
Normal Function of Adipose Tissue
J Kreider, 2006
What happens when fat proliferates
abnormally? (OBESITY)

Cytokines
Cytokines
Chronic inflammation develops
Metabolic syndrome is characterized by chronic inflammation

What cytokines (adipokines) are involved in producing the pro-
inflammatory state of Metabolic Syndrome?


TNF-alpha
Interleukin-6
Interleukin-2
*C-reactive protein
How did we learn about TNF-alpha in the
laboratory?
1. In vivo:
2. In vitro assays:
Induce obesity and insulin resistance,
measure TNF-alpha
Block TNF-alpha using antibodies, induce obesity
Does the mouse develop insulin resistance?
FOOD
Ob/Ob mouse
Remove a protein completely by
removing the gene
Normal mouse

Knock-out TNF-alpha, induce obesity
Does the mouse become insulin resistant?
FOOD
Add TNF-alpha to normal adipocytes
Do the cells become insulin resistant?
Insulin
Adipocyte
High Blood Sugar
Insulin Released from Pancreas
Insulin
Adipocyte
Insulin binds to the insulin
receptor on adipocytes
Insulin
Adipocyte
Glucose is taken up by
the cell for storage
Blood glucose decreases
OBESITY

Cytokine
s
TNF-alpha
Insulin
Adipocyte
TNF-alpha alters the way the
insulin receptor works
Insulin
Adipocyte
Tumor necrosis factor-alpha
Increases to abnormal levels with obesity
Greatly increased in patients with Metabolic Syndrome
Interleukin 6
Most elevated pro-inflammatory adipokine
Insulin
Adipocyte
*Release is induced by TNF-alpha and IL-6 itself
TNF-alpha
IL-6
IL-6
SUMMARY

1. Insulin cannot work
effectively





2. Free Fatty Acids are
released into blood stream
Insulin
Adipocyte
Adipocyte
Adipose tissue expands
Proinflammatory
Cytokines Released
Glucose Uptake
Decreases
Pancreas Increases
Insulin Production
Hyperinsulinemia
Triglycerides Released
to Blood Stream
Cardiovascular Disease
Hyperglycemia
Blood Glucose
Levels Increase