METABOLISM of ADIPOSE TISSUE 2. LF UK Prof. Rudolf Poledne, PhD.

TYPES OF ADIPOSE TISSUE  brown adipose tissue  subcutaneous adipose tissue  visceral adipose tissue

ADIPOSE TISSUE FUNCTIONS:  thermal isolation  mechanical protection  reserve of energy  endocrine organ  pro- and antiinflammation function

AEROBIC OXIDATION OF FFA GLYCOLEN ATP + GP HOUR MUSCLE ENERGY RESOURCES

ADIPOSE TISSUE AS ENDOCRINE ORGAN FRACTION 3 NON –FAT FRACTION TNF α FRACTION 2 FLOATING FRACTION FRACTION 1 FILTER – RETAINED FRACTION WHITE ADIPOSE TISSUE COLLAGENASE DIGESTION FILTER 200 μm MESH CENTRIFUGE FILTRATE LEPTIN, ADIPONECTIN PAI – 1, IL – 8, VEGF, IL – 6 IL – 1β, IL – 10, TNFα, ADIPONECTIN ADIPOCYTES STROMAL VASCULAR CELLS (MONOCYTES/MACROPHAGES/PREADIPOCYTES) ADIPOSE – TISSUE MATRIX (ENDOTHELIAL, SMOOTH MUSCLE AND FIBROBLAST CELLS)

DAMP signály při excesivní obezitě J. Clin. Invest. 2006;116:33-35

Reserve of energy

Dyslipoproteinemia VLDL1 – high density LDL Interleukin 6, adiponectin VCAM, ICAM Monocyte changes after pasage of adipose tissue Aterogenic effect of visceral adipose tissue

CHYLOM. REMNANTS CHYLOMICRONS INTESTINE LIVER FFA MUSCLE FFA ATP FFA 2 – MG LPL LRP FFA FATP ADIPOSE T. TG apoB – 48 Exogenous fat intake

triglycerides cholesterol-esters APO B 48 APO A I APO E APO A V PL FC

Postprandial lipoprotein metabolism C lipoprotein lipase CR CR C C (( LRP LRP LDL R

triglycerides cholesterol-esters APO B 48 APO A I APO E APO A V nascent. HDL remnant

SAFA inflammation stimulation TLR 4 PUFA ω3 inflammation inhibition TLR 4

SAFA TLR4 NF  B IL-6 IL-8 ACCELERATION OF PROINFLAMMATION STATUS CRP ADIPOCYTE MACROPHAGE

SAFA PUFA n = 9 4 weeks Diet: fat total 40% Animal fats 30% Animal fats 10%

CRP concentration CRP concentration mmol/l p < 0,05

GLUCOSE IDL FFA ADIPOSE TISSUE FFA TG VLD L LDL LDL R FC CHO L. apoB 100 FFA HEPATOCYTE BILE A. PERIPHERAL CELLS

VLDL HSL FASTING LPL apoB 100 ATP FFA FFA TG FFA

INSULIN HSL PERILIPIN CATECHOLAMINES X

VLDL OBESITY – LOW PHYSICAL ACTIVITY – INSULIN RESISTANCE VMK OXIDATP GLUCSE CHYLOM. TG HSL FFA TG FFA X

SAFA inhibuje tvorbu receptorů LDL-rec. zvyšuje koncentraci cholesterolu PUFA ω3 stimuluje tvorbu receptorů LDL-rec. snižuje koncentraci cholesterolu

LDL (small dense) STEATOSIS – NAFL – NASH OXID TG VLDL (large) FFA X apoB 100

Metabolismus TG-bohatých lipoproteinů Normální regulace Inzulínová rezistence TG TG VLDL 1 IDL LDL VLDL IDL LDL

Adipose tissue as endocrine organ

Dyslipoproteinemia VLDL1 – high density LDL Interleukin 6, adiponectin VCAM, ICAM Monocyte changes after pasage of adipose tissue Aterogenic effect of visceral adipose tissue

EFFECT OF LEPTIN LEPTIN FOOD INTAKE IL6 synthesis HYPOTHALAMUS FA synthesis TG synthesis FA synthesis FA oxidation Permeability

INFLUENCE OF ADIPONECTIN ADIPONECTIN TNF α MØ GLUCO- NEOGENESIS OXIDATION FA PERMEABILITY INTERLEUKIN-6

BMI AND RISK OF MI (US Nurses Study) BMIRRSignif. BMIRRSignif. 21 – – – * 23 – * 25 – ** 25 – ** 27 – *** 27 – *** > 302.7*** > 302.7***

Pro- and antiinflammation functions

Dyslipoproteinemia VLDL1 – high density LDL Interleukin 6, adiponectin VCAM, ICAM Monocyte changes after pasage of adipose tissue Aterogenic effect of visceral adipose tissue

PROINFLAMMATION STATUS POTENTIATION MØ IL 6 TNFα MCP TNF α Il6 NF ƙ B SYNTHESIS

Arterial wall Adipose tissue Monocyte run through adipose tissue Proinflammatory status CRP

Protocol of the study: Volunteers: 40 women aged yrs BMI over 28 9 weeks of dietary intervention (energy intake to 8000 kJ) 9 weeks of controlled physical activity (puls frequence 65% max. PF)

ns * Energy animal fat vegetable fat total fat baseline after int. [mmol/l] Energy and fat intake

**** ns WHRwaisthips baseline after intervention [cm] Changes in anthropometric parameters

ns * Trigyceridestotal cholesterol LDL cholesterol HDL cholesterol baseline after int. [mmol/l] Changes in lipoprotein parameters

ns * ** * GlycemiaInsulinLeptinLeptin rec baseline after int. [%] Changes in glycemia, insulin and leptin

ns *** **** systolic BPdiastolic BPpulses baseline after int. [%] Changes in blood pressure and pulses

C-reactive protein p < 0,0002 4,31 ± 3,71 3,01 ± 3,12

In addition to energy reserve adipose tissue is:  an important endocrine organ  influencing of proinflammation status and accelerating atherogenesis