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 Congenital 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 Anal dysf. Child 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 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 forrer 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)

2 Hva skjer fysiologisk ( i kroppen ) når fedme utvikles Histological composition of Nerve endings Capillaries Adipocytes Adipocyte (Fat cell) Extracellular matrix Immune cell (,T-cells, etc) Histological composition of Nerve endings Capillaries The fundamental type of lipid: Adipocyte (Fat cell): Filled with triglycerides Fatty acids: Extracellular matrix Immune cell (,T-cells, etc) Tore Henriksen 2006 Synthesis of 3 free fatty acids (Triacylglycerols) Tore Henriksen 2006

3 In the adipocytes triglycerides are synthesized continuously In the adipocytes triglycerides are split into fatty acids glycerol continuously lipases Free fatty acids Free fatty acids Basic principle of fat metabolism in adipose tissue Endocrinology of adipose tissue: Factors produced by adipocytes : adipokines () into blood Fat cell () (hormone Synthesis sens.lipase) () (: VLDL), from blood Capillary (Lipoprotein lipase) () into blood Hormones: Leptin, Adiponectin Visfatin Resistin Adipocyte (fat cell) () Synthesis () Cytokines: TNFα MCP-1 (CCL2) IL1β IL-1Rα (antiinflam.) IL-10 (antiinflam.) (), From blood Other: RBP4 PAI-1 Prostaglins Endocrinology of adipose tissue: Factors acting on the adipocytes Fat cell Summary: is a metabolically hormonally very active! () into blood () Synthesis () (), From blood Adipocytes Hormones etc affecting adipose tissue: (Nor-)adrenalin Cortisol Growth factors Cytokines Etc

4 has major effects on (interacts with) other organs has major effects on (interacts with) other organs Placenta Free fatty acids are continuously released from adipose tissue In : Free fatty acids are synthesized back to triglycerides secreted to circulation (as VLDL), transported to adipose tissue striated muscles (etc) lipolysis Thus: Fatty acids are continuously being turned over in a loop lipolysis Abdominal () fat goes through the portal system. lipolysis

5 In obesity there is an increased size number of adipocytes: 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 amount mass of adipose tissue there is an increasing presence of immune cells, like Macrophages With increasing adiposity there is increasing Why leads increasing adiposity increasing Inflammation? Increased amount of fatty acids of, how is it linked?? Increased amount of fatty acids of, how is it linked?? Oxidized fatty acids Toll like Receptors (TLR4) () Toll like Receptors (TLR4) () MCP-1 Activation of the Recruitment of

6 When (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 leads to increased flux of in the circulation: Recruitment of Tore Henriksen 2012 Increased flux of fatty acids: Fat deposition in liver: In the liver: Fatty liver! Fat deposition in liver leads to 2. Fatty liver, Inflammation! Overall consequence: Increased circulation of inflammatory cytokines etc, both from liver adipose tissue In the liver: 1: Fatty liver! 2. Inflammation! Cytokines, etc Adopose tissue Cytokines, etc Inflammation! In the liver: 1: Fatty liver! 2. Inflammation! Resulting in systemic inflammatory response Inflammation!

7 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 resistance/ diabetes Glucose Systemic inflammatory response receptor Endothelial activation Preeclampsia Tore Henriksen 2012 Systemic inflammatory response resistance/ diabetes Glucose receptor Tore Henriksen 2012 Endothelial activation Preeclampsia Placenta Placental inflammatory reaction Increased fatty acid transport? Glucose transport? /obesity/systemic pregnancy complications. Maternal overweight/ obesity/ Systemic Endothelial activation resistance In this pregnancy: Miscarriage Preeclampsia Gestational diabetes Thromboembolism Congenital malformations Intrauterine fetal death Macrosomia Placental dysfunction Long term: Maternal Cardiovascular. Child Cancer? Cardiovascular? Takk!