METABOLISM of ADIPOSE TISSUE

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

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

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

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

5

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

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

8 Reserve of energy

9

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

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

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

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

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

15 SAFA inflammation stimulation TLR 4 PUFA ω3 inflammation inhibition TLR 4

16 ADIPOCYTE SAFA TLR4 MACROPHAGE NFkB IL-6 IL-8 ACCELERATION OF PROINFLAMMATION STATUS CRP

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

18 CRP concentration mmol/l p < 0,05

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

20 FASTING FFA FFA HSL TG LPL ATP FFA LPL apob 100 VLDL

21 CATECHOLAMINES HSL PERILIPIN INSULIN X

22 OBESITY LOW PHYSICAL ACTIVITY INSULIN RESISTANCE HSL GLUCSE CHYLOM. FFA TG VMK TG ATP OXID X FFA TG VLDL

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

24 STEATOSIS NAFL NASH OXID X FFA TG apob 100 VLDL (large) LDL (small dense)

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

26 Adipose tissue as endocrine organ

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

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

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

30 BMI AND RISK OF MI (US Nurses Study) BMI RR Signif * ** *** > ***

31 Pro- and antiinflammation functions

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

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

34

35

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

37 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)

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

39 Changes in anthropometric parameters [cm] **** 100 baseline ns **** after intervention 70 WHR waist hips

40 Changes in lipoprotein parameters [mmol/l] 6 5 ns 4 3 ns baseline after int. 2 1 ns * 0 Trigycerides total cholesterol LDL cholesterol HDL cholesterol

41 Changes in glycemia, insulin and leptin [%] * ns * ** Glycemia Insulin Leptin Leptin rec baseline after int.

42 Changes in blood pressure and pulses [%] ns **** *** systolic BP diastolic BP pulses baseline after int.

43

44 C-reactive protein [mg/l] baseline p < 0,0002 4,31 ± 3,71 3,01 ± 3,12 after intervention

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

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