Overvekt, mer enn bare overvekt
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1 Overvekt, mer enn bare overvekt Kurs Overvekt i svangerskap og fødsel Overvekt/fedme i historisk perspektiv I løpet av1-2 generasjoner har det vært en økning i forekomsten av fedme som er historisk uovertroffen. Mennesket har levd på jorden i generasjoner! Tore Henriksen Oslo University Hospital University of Oslo Oslo, Norway Fedme og svangerskap: Konsekvenser på kort og lang sikt. For mor og barn Maternal overweight/ obesity Short term Consequences (this pregnancy) Long term Consequences (future life) Miscarriage Preeclampsia Gestational diabetes Thromboembolism Congential malformations Intrauterine fetal death Delivery complications (Prolonged labour, Fetal distress, Vacuum/forceps, Cesarean section) Neonate injuries Maternal injuries/infections Need for neonatal intensive care Less breast feeding Maternal Overweight Diabetes Anal dysf. Child Diabetes Overweight Cancer Cardiovascular? Det å studere fedme(epidemien) har tre perspektiver: Årsakene til at fedme utvikler seg i en befokning Hva skjer fysiologisk når fedme utvikles Hvilke helsemessige konsekvenser har fedme
2 Grunnleggende fakta om overvekt/fedme Årsaker til en fedmepidemi. Regulering av energi-inntak, gener og miljø Overvekt/fedme er et resultat av samspill mellom gener og miljø. Genene forandrer seg ikke på 1-2 generasjoner. Miljøet må derfor ha spilt avgjørende rolle for den overvektsepidemien vi har. Miljø: Fosterliv (Mors) Ernæring Miljøgifter Fysisk aktivitet Psykologiske forhold Samfunsmessige forhold Klimaforhold? Reguleringen av mat- (energi-)inntaket består i komplekst samspill mellom en rekke organer Gener, og geners aktivitet (epigentikk) Hva skjer fysiologisk ( i kroppen ) når fedme utvikles Histological composition of Adipose tissue Nerve endings Capillaries Adipocytes Adipocyte (Fat cell) Extracellular matrix Immune cell (macrophages,t-cells, etc)
3 Histological composition of Adipose tissue Nerve endings Capillaries The fundamental type of lipid: Adipocyte (Fat cell): Filled with triglycerides Fatty acids: Extracellular matrix Immune cell (macrophages,t-cells, etc) Tore Henriksen 2006 Glycerol Synthesis of 3 free fatty acids (Triacylglycerols) Tore Henriksen 2006
4 In the adipocytes triglycerides are synthesized continuously In the adipocytes triglycerides are split into fatty acids and glycerol continuously lipases Glycerol Free fatty acids Glycerol Free fatty acids Basic principle of fat metabolism in adipose tissue Endocrinology of adipose tissue: Factors produced by adipocytes : adipokines Adipocyte (fat cell) () into blood Fat cell () (hormone Synthesis sens.lipase) Glycerol () (: VLDL), from blood Capillary (Lipoprotein lipase) () into blood Hormones: Leptin, Adiponectin Visfatin Resistin () Synthesis () Cytokines: TNFα MCP-1 (CCL2) IL1β IL-1Rα (antiinflam.) IL-10 (antiinflam.) (), From blood Other: RBP4 PAI-1 Prostaglandins
5 Endocrinology of adipose tissue: Factors acting on the adipocytes Fat cell Summary: Adipose tissue is a metabolically and hormonally very active! () into blood () Synthesis (), From blood () Adipocytes Hormones etc affecting adipose tissue: Insulin (Nor-)adrenalin Cortisol Growth factors Cytokines Etc Adipose tissue has major effects on (interacts with) other organs Adipose tissue has major effects on (interacts with) other organs Adipose tissue Adipose tissue Placenta
6 Free fatty acids are continuously released from adipose tissue In : Free fatty acids are synthesized back to triglycerides and secreted to circulation (as VLDL), and transported to adipose tissue and striated muscles (etc) lipolysis Thus: Fatty acids are continuously being turned over in a loop lipolysis Abdominal () fat goes through the portal system. Portal vein lipolysis
7 In obesity there is an increased size and number of adipocytes: With increasing amount mass of adipose tissue there is an increasing presence of immune cells, like Macrophages macrophages With increasing amount mass of adipose tissue there is an increasing presence of immune cells, like Macrophages With increasing amount mass of adipose tissue there is an increasing presence of immune cells, like Macrophages With increasing adiposity there is and increasing inflammation Why leads increasing adiposity increasing Inflammation? macrophages macrophages
8 Increased amount of fatty acids and of macrophages, how is it linked?? Increased amount of fatty acids and of macrophages, how is it linked?? Oxidized fatty acids Toll like Receptors (TLR4) () Toll like Receptors (TLR4) () MCP-1 Activation of the macrophages Recruitment of macrophages When macrophages and (other immune cells) come: Toll like Receptors (TLR4) MCP-1 Inflammatory () response in adipose tissue Release of pro-inflammatory Cytokines, like TNF, IL-1β, etc Adiposity inflammation leads to increased flux of in the circulation: Portal vein and inflammation Recruitment of macrophages Tore Henriksen 2012
9 Increased flux of fatty acids: Fat deposition in liver: In the liver: Fatty liver! Portal vein and inflammation Fat deposition in liver leads to 2. inflammation Fatty liver, Inflammation! Portal vein and inflammation Overall consequence: Increased circulation of inflammatory cytokines etc, both from liver and adipose tissue In the liver: 1: Fatty liver! 2. Inflammation! Cytokines, etc Adopose tissue Cytokines, etc and Inflammation! In the liver: 1: Fatty liver! 2. Inflammation! Resulting in systemic inflammatory response and Inflammation!
10 Consequences of an adiposity induced inflammatory responses in pregancy De metabolske endringene og den systemiske inflammasjonen som utvikles ved fedme har også konsekvenser for placenta og foster Insulin resistance/ diabetes Glucose Systemic inflammatory response Insulin receptor Endothelial activation Preeclampsia Tore Henriksen 2012 Systemic inflammatory response Insulinresistance/ diabetes Glucose Tore Henriksen 2012 Insulin receptor Endothelial activation Preeclampsia Placenta Placental inflammatory reaction Increased fatty acid transport? Glucose transport? Overweight/obesity/systemic inflammation and pregnancy complications. Maternal overweight/ obesity/ Systemic inflammation Endothelial activation Insulin resistance In this pregnancy: Miscarriage Preeclampsia Gestational diabetes Thromboembolism Congential malformations Intrauterine fetal death Macrosomia Placental dysfunction Long term: Maternal Overweight Diabetes Cardiovascular. Child Diabetes Overweight Cancer? Cardiovascular? Takk!
Overvekt, mer enn bare overvekt
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