mmc1 fatty acid chemistry and disease.ppt

Final lectures to be studied

1. “Sick Fat,” Metabolic Disease,
and Atherosclerosis
Harold E. Bays, MD
Medical Director and President,
Louisville Metabolic and Atherosclerosis Research Center (L-MARC),
Louisville, KY
Sponsored by AstraZenecaGraphical support by Scientific Connexions

2. “Average” Cholesterol Is Not Necessarily Normal50 70 90 110 130 150 170 190 210
Adult Am erican
San
Pygm y
!Kung
Inuit
Hazda
Night m onkey
How ler m onkey
Baboon
African elephant
Black rhinoceros
Peccary
Boar
Horse
HUNTER-GATHERER
HUMANS
WILD
PRIMATES
WILD
MAMMALS
URBANIZED
HUMANS
Mean Total Cholesterol, mg/dL
Modified with permission from O’Keefe JH Jr et al. J Am Coll Cardiol.2004;43:2142–2146.
Bays HE. Am J Med.2009;122:S26S37.
Text Figure 1

3. BMI and Prevalence of Metabolic Disease
NHANES 1999-2002
18.5-24.925-26.927-29.930-34.935-39.940
0
10
20
30
40
50
60
70
Diabetes Mellitus
Hypertension
Dyslipidemia
OVERALL<18.5
1.7
22.3
24
4.2
17.6
38.2
5.7
25.3
53.1
10.1
30.8
62.2
12.2
39.3
68
16.4
44
67.5
27.3
51.3
62.5
9
28.9
52.9
Body Mass Index (BMI)
% of Patients
LeanNormal Overweight Obese
Modified with permission from Bays HE et al. Int J Clin Pract.2007;61:737–747; © 2007 Wiley Blackwell.
Bays HE. Am J Med.2009;122:S26S37.
Text Figure 2

4. BMI Among Patients With Metabolic
Disease NHANES 1999-2002
18.5Diabetes Mellitus
13.8%
21.7%23.2%
0.4%
9.9%
17.1%
13.9% Hypertension
23%
11.7%
7.6%
1.7%
21.9%
13.4%
20.7% Dyslipidemia
15.1%
5.1%
9.5%
21.5%
22.3%
25.5%
0.9%
Body Mass Index (BMI)
18.5-24.9 25-26.9 30-34.9 35-39.9 4027-29.9
Modified with permission from Bays HE et al. Int J Clin Pract.2007;61:737–747; © Wiley Blackwell.
Bays HE. Am J Med.2009;122:S26S37.
Lean Normal Overweight Obese
Text Figure 3

5. Reprinted with permission from Bays H et al. Expert Rev Cardiovasc Ther,2006;4:871–895; © 2006 Future Drugs Ltd.
Bays HE. Am J Med.2009;122:S26S37.
Adipocyte Size and Body Fat Distribution Help to Define “Sick”
Versus “Healthy” Adipose Tissue
Text Figure 4

6. Contributors and Consequences of Pathogenic
Adipose Tissue (Adiposopathy)
Reprinted with permission from Bays H et al. Future Lipidology.2006;1:389–420, © 2006 Future Drugs Ltd.
Bays HE. Am J Med.2009;122:S26S37.
Text Figure 5
FFA = free fatty acid; HDL = high-density lipoprotein; LDL = low-density lipoprotein

7. Navigating the Consequences of “Sick Fat”
Bays HE. Am J Med.2009;122:S26S37.
Text Figure 6

8. NCEP Definition of Metabolic Syndrome*
Risk factor Defining level
Abdominal obesity
(waist circumference)
102 cm (40 in) for men
88 cm (35 in) for women
Triglycerides 150 mg/dL
HDL-C 40 mg/dL (men)
50 mg/dL (women)
Blood pressure 130/85 mm Hg
Fasting glucose 100 mg/dL
Modified with permission from NCEP. JAMA. 2001;285:2496–2497.
Grundy SM et al Circulation. 2005;112:2735-2752.
Bays HE. Am J Med.2009;122:S26S37.
Text Table 3
*Presence of 3 of these components.

9. Genesis of the Metabolic Syndrome
Lipid Profile
Reprinted with permission from Bays H et al. Future Lipidology.2006;1:389–420, © 2006 Future Drugs Ltd.
Bays HE. Am J Med.2009;122:S26S37.
Text Figure 7

10. Examples of CHD Risk Factors
History
•Prior diagnosis of CHD
•Carotid artery disease
•Peripheral artery disease
•Abdominal aortic aneurysm
Nonmodifiable factors
•Age: Men 45 years, women
55 years
•Family history: CHD in a 1st-
degree relative aged 55 years
(male) or 65 years (female)
Metabolic disease
•Type 2 diabetes mellitus
•Hypertension
•Dyslipidemia
Modifiable factors
•Cigarette smoking
•Pathogenic adipose tissue
(adiposopathy)*
*The potential of adipose tissue to be an active endocrine,
immune, and pathogenic organ is not universally accepted.
Bays HE. Am J Med.2009;122:S26S37.
Text Table 2

11. *Not currently available in the United States.
= Increased;= decreased;? = unknown;― = neutral effect; PPAR-γ= peroxisome proliferator–activated receptor gamma.
Modified with permission from Bays et al. Curr Treat Options Cardiovasc Med.2007;9:259-271.
Bays HE. Am J Med.2009;122:S26S37.
Treatments for Adiposopathy
May Affect Glucose Metabolism, Blood Pressure, and
Lipid Metabolism
May Affect
Glucose
Metabolism
Intervention
Visceral
Adipose Tissue
Free Fatty
Acids Leptin Adiponectin
Tumor Necrosis
Factor-Alpha
Nutrition and
physical
activity
    
PPAR-γ
agonists
(pioglitazone,
rosiglitazone)
or― or
―
 
Orlistat
    
Sibutramine
  or― ?
Cannabinoid
receptor
antagonists*
    
Text Table 4 (part 1)

12. Treatments for Adiposopathy
May Affect Blood Pressure May Affect Lipid Metabolism
Intervention
Renin-Angiotensin-Aldosterone
Enzymes Androgens Estrogens
Nutrition and
physical activity  (women)
(men)
or―
(men)
PPAR-γ agonists
(pioglitazone,
rosiglitazone)
―
 or―
(men)
Orlistat
? (women)?
Sibutramine
? (women)?
Cannabinoid receptor
antagonists* ? ? ?
*Not currently available in the United States.
= Increased;= decreased;? = unknown;― = neutral effect; PPAR-γ= peroxisome proliferator–activated receptor gamma.
Modified with permission from Bays et al. Curr Treat Options Cardiovasc Med.2007;9:259-271.
Bays HE. Am J Med.2009;122:S26S37.
Text Table 4 (part 2)

13. PEARLS FOR CLINICAL GUIDANCE
•To reduce coronary heart disease (CHD) risk, encourage appropriate nutrition
and healthy lifestyle habits, and, if needed, recommend pharmaceutical agents
that improve modifiable risk factors.
•Even if a metabolic parameter is a risk factor for CHD, an isolated improvement
in this CHD risk factor may not always reduce CHD events.
•Therapies that improve glucose metabolism in hyperglycemic patients, reduce
blood pressure in hypertensive patients, and improve lipid levels in dyslipidemic
patients may reduce CHD risk, although it is unclear whether isolated
improvements in some of these CHD risk factors independently reduce CHD
risk. Furthermore, the degree to which therapies that improve CHD risk factors
actually reduce CHD risk may depend on how these CHD risk factors are
improved.
•Adipose tissue functions as an active endocrine and immune organ that, when
“sick” (as often occurs with weight gain) may contribute to metabolic disease.
•Adipocyte hypertrophy and visceral adiposity (adiposopathy) may result in
adverse metabolic and immune consequences that contribute to major CHD risk
factors (e.g., high glucose levels, high blood pressure, dyslipidemia).
•Reducing adipocyte hypertrophy and visceral adiposity through appropriate
nutritional measures and lifestyle interventions may improve the metabolic
health of patients and thus reduce CHD risk.
Bays HE. Am J Med.2009;122:S26S37.