béo phì và tác hại

béo phì và tác hại

Anna Tzontcheva, MD, PhD

Chair of Clinical Laboratory and Clinical

immunology, Medical University – Sofia, Bulgaria

Abdominal obesity, diabetes and

cardiovascular risk

15 th BCLF Congress, 4-7 September 2007

Antalya, Turkey

http://www.biyokimya.org/belge/sunu_bclf/06.09.2007/Tzontcheva.ppt

• Obesity , particularly

intra-abdominal (visceral) obesity, is a leading cause of cardiovascular disease (CVD), insulin resistance, type 2 diabetes, dyslipidaemia, inflammation and thrombosis

• A useful indicator for visceral fat

is waist circumference , which is associated with all-cause

mortality Pro-inflammatory

adipokines play a causal role in the development of pathologies associated with insulin

resistance, type 2 diabetes and CVD.

Hormonal Control of Eating

Changing Portion Sizes

National Geographic, August 2004

2004

2004 2004

2004

2004

The Fat Cell Is a Veritable Endocrine

• Fat cells are continually absorbing or releasing

substances in response to the body’s energy needs

• Fat cells are better adapted to preserving calories

than shedding them

Source: Underwood A, Adler J, Hand K, Ulick J What You Don’t Know About Fat Newsweek 2004;144:40-47

Fat Cell

• A protein is also called ADIPOQ, gelatine-binding

28, Acrp30, discovered in 1995

• A peptide hormone made by adipocytes in response

to high fat reserves:

Increases FA uptake by myocytes and the rate of

FA oxidation.

Slows FA synthesis in the liver.

Slows gluconeogenesis in the liver.

Acts through AMP-dependent protein kinase

(AMPK).

• Humans who are obese or who suffer from Type II

diabetes show reduced levels of adiponectin.

• Drugs (thiazolidinediones) used to treat Type II

diabetes elevate expression of adiponectin.

Adiponectin - structure

Adiponectin action : activation AMPK

Molecular Mechanisms of Adiponectin Action

Kadowaki et al Endocrine Reviews 26 (3): 439 - 451, 2005

Adiponectin R1 and R2 are Expressed in Heart, Liver, Kidney, Skeletal Muscle and Other Tissues

Leptin Action

• Suppresses appetite via production of α

-melanocyte-stimulating (α-MSH) hormone, which triggers the next neuron in the circuit to send the

“Stop eating!” signal.

• Stimulates the sympathetic nervous system :

Increases bp.

Increases heart rate.

Increases thermogenesis via uncoupling of electron transport.

• Leptin production depends on the number and size of adipocytes.

PI3 Kinase

Protein

Produced in adipocytes

Family of proteins with C-terminal rich of cysteine

The invention of resistin as a novel factor secreted by fat cells with an impact on insulin sensitivity was proposed as a new

mechanism to explain the pathogenic sequence of

adipocyte-obesity-insulin resistance Resistin is a cysteine-rich 12.5 kDa polypeptide, with unclear role in the pathogenesis of obesity-

mediated insulin resistance and type 2 diabetes mellitus Recent studies in murine models suggest that resistin (also called Fizz3), secreted by adipocytes, may represent the long-sought link

between obesity and insulin resistance

In 2004, Fukuhara et al identified a molecule that is expressed at much higher levels in visceral fat than in subcutaneous fat which was named visfatin [27] This adipokine is highly expressed in the visceral adipose tissue of both humans and rodents Visfatin was

Visfatin

• In 2004, Fukuhara et al identified a molecule that is

expressed at much higher levels in visceral fat than in

subcutaneous fat which was named visfatin

• This adipokine is highly expressed in the visceral adipose

tissue of both humans and rodents Visfatin was found to be identical to a cytokine expressed by lymphocytes - the pre-B cell colony-enhancing factor (PBEF)

• Visfatin binds to the insulin receptor at a site distinct from

insulin and exerts hypoglycemic effect by reducing glucose

release from hepatocytes and stimulating glucose utilization in peripheral tissues

• Since insulin-mimetic actions of visfatin may be part of the

feedback regulation of glucose homeostasis, a hypothesis may

be raised that visfatin concentrations are influenced by

glucose or insulin blood levels in humans This possibility

offers new therapeutic options for diabetics

IL6 PAI-1

adiponectin

leptin

Adipokines Mediate Insulin Resistance

and Inflammation

angiotensinogen

FFA visfatin

Metabolic Syndrom - Diagnostic Criteria

Three or more of:

• Central obesity: waist >102

Proposed IDF Criteria 2005 (a)

Central Obesity

Waist circumference (ethnic specific)

Plus two (2) of the following:

• Raised triglyceride (>1.7 mmol/l)

Inflammation

Thrombosis Oxidation

Atherosclerosis Atherosclerosis Atherosclerosis

Unstable plaque Inflammation, Fibrosis Cap Thrombosis and Rupture

Event

Hyperinsulinemia Metabolic Syndrome Impaired GlucoseTolerane Type 2 Diabetes

Hsueh WA, Law R AJC, 2003

Process of Atherosclerosis in Insulin Resistance

Adapted from Steinberg H et al Diabetes 2000;49:1231.

Vascular dilation

NO productionVascular dilation

Elevated CRP Levels in Obesity:

Effects of Weight Loss in Obese Women on

After very low calorie diet

(mean BMI reduction 2.1 kg/m 2 ; mean reduction in body fat mass 4 kg)

p=0.05

p=0.6

p=0.14

The Science of Obesity

Is Complex and in Its Infancy

1994 – Leptin was discovered at Rockefeller University

“We like to think that eating is a voluntary act But the

amount you eat is controlled in part by how much fat you have.”

– Dr Michael Schwartz, University of Washington

Researchers and scientists took a fresh look at obesity – was it more than a

reflection of greed and weak will?

Sources: Rockefeller Researchers Clone Gene for Obesity December 1, 1994 Available at:

http://www.healthpolitics.com/home.asp?show=all

Underwood A, Adler J, Hand K, Ulick J What You Don’t Know About Fat Newsweek 2004;144:40-47

for risk factors for diabetes and

cardiovascular disease.

for the reduction in the morbidity and mortality associated with multiple risk factors and the metabolic syndrome.

“In the human body, as in the world, if you control fuel resources, you

influence a lot of other things as well.”

– Dr Gökhan Hotamisligil, Harvard School of Public Health

Thank you !