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
MUSCLE ENERGY RESOURCES ATP + GP AEROBIC OXIDATION OF FFA GLYCOLEN 0 1 2 3 4 5 6 HOUR
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
DAMP signály při excesivní obezitě J. Clin. Invest. 2006;116:33-35
Reserve of energy
Aterogenic effect of visceral adipose tissue Dyslipoproteinemia VLDL1 high density LDL Interleukin 6, adiponectin VCAM, ICAM Monocyte changes after pasage of adipose tissue
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
APO E PL triglycerides APO A V FC APO A I cholesterol-esters APO B 48
( ( Postprandial lipoprotein metabolism C C C lipoprotein lipase LRP LDL R CR CR LRP LDL R
APO E APO A V nascent. HDL triglycerides APO B 48 cholesterol-esters APO A I remnant
SAFA inflammation stimulation TLR 4 PUFA ω3 inflammation inhibition TLR 4
ADIPOCYTE SAFA TLR4 MACROPHAGE NFkB IL-6 IL-8 ACCELERATION OF PROINFLAMMATION STATUS CRP
n = 9 SAFA SAFA n = 9 PUFA PUFA 4 weeks 4 weeks Diet: fat total 40% Animal fats 30% Animal fats 10%
CRP concentration mmol/l p < 0,05
HEPATOCYTE GLUCOSE FFA BILE A. FFA CHO L. LDLR TG VLD L apob 100 ADIPOSE TISSUE FC LDL LDL R IDL FFA PERIPHERAL CELLS
FASTING FFA FFA HSL TG LPL ATP FFA LPL apob 100 VLDL
CATECHOLAMINES HSL PERILIPIN INSULIN X
OBESITY LOW PHYSICAL ACTIVITY INSULIN RESISTANCE HSL GLUCSE CHYLOM. FFA TG VMK TG ATP OXID X FFA TG VLDL
SAFA inhibuje tvorbu receptorů LDL-rec. zvyšuje koncentraci cholesterolu PUFA ω3 stimuluje tvorbu receptorů snižuje koncentraci cholesterolu LDL-rec.
STEATOSIS NAFL NASH OXID X FFA TG apob 100 VLDL (large) LDL (small dense)
Metabolismus TG-bohatých lipoproteinů Normální regulace Inzulínová rezistence TG TG VLDL VLDL 1 IDL IDL IDL LDL LDL
Adipose tissue as endocrine organ
Aterogenic effect of visceral adipose tissue Dyslipoproteinemia VLDL1 high density LDL Interleukin 6, adiponectin VCAM, ICAM Monocyte changes after pasage of adipose tissue
EFFECT OF LEPTIN LEPTIN HYPOTHALAMUS FOOD INTAKE FA synthesis FA synthesis TG synthesis IL6 synthesis FA oxidation FOOD INTAKE Permeability
INFLUENCE OF ADIPONECTIN ADIPONECTIN GLUCO- NEOGENESIS INTERLEUKIN-6 OXIDATION FA TNF α PERMEABILITY MØ
BMI AND RISK OF MI (US Nurses Study) BMI RR Signif. 21 22 1.0 23 25 1.3 * 25 27 1.6 ** 27 30 1.8 *** > 30 2.7 ***
Pro- and antiinflammation functions
Aterogenic effect of visceral adipose tissue Dyslipoproteinemia VLDL1 high density LDL Interleukin 6, adiponectin VCAM, ICAM Monocyte changes after pasage of adipose tissue
PROINFLAMMATION STATUS POTENTIATION SYNTHESIS NF ƙ B TNFα IL 6 TNF α MØ TNFα Il6 MCP
Monocyte run through adipose tissue Arterial wall Proinflammatory status CRP Adipose tissue
Protocol of the study: Volunteers: 40 women aged 25-35 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)
Energy and fat intake [mmol/l] 90 12000 80 70 60 50 40 ns ns * 10000 8000 6000 baseline after int. 30 20 10 ns 4000 2000 0 0 Energy animal fat vegetable fat total fat
Changes in anthropometric parameters [cm] 120 110 **** 100 baseline 90 80 ns **** after intervention 70 WHR waist hips
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
Changes in glycemia, insulin and leptin [%] 150 140 130 120 110 100 90 80 70 60 * ns * ** Glycemia Insulin Leptin Leptin rec baseline after int.
Changes in blood pressure and pulses [%] 105 100 95 90 85 80 75 70 65 60 ns **** *** systolic BP diastolic BP pulses baseline after int.
C-reactive protein [mg/l] 16 14 12 10 8 6 4 2 0 baseline p < 0,0002 4,31 ± 3,71 3,01 ± 3,12 after intervention
In addition to energy reserve adipose tissue is: an important endocrine organ influencing of proinflammation status and accelerating atherogenesis