L14 contr appet, metab synd, DOHAD Flashcards
LO2: disc horms in in appet contr.
-horms sigs from gut to hypoth:
Ghrelin rel from stom wall when empty. Stom excit prim arcuate neurons= stim appet. Full stretch prev ghrelin rel.
pep tyr tyr PYY- 36 AA pep horm rel in ileum and colon in resp to feed. Inhibs excit prim arcuate, stims inhib = decr appet. Prom siation. Infec PYY to mouse= anorexic, blunted PYY resp to food in obese.
-horm sigs from bod to hypoth-
Leptin- pep horm rel to blood by adipoc. 2 aff arcuate- stims inhib POMC neurones and inhibs excit AgRP/NPY=decr appet. Induces exp uncoup prots mito= heat.
Amylin imp in combin leptin- unclear role. Pep horm sec by beta cells panc- decr appet, decr glucagon sec, and slow gastric emp. Pramlintide analogue appr T2DM tx.
Insulin- supp appet sim way to leptin. Less imp.
-contr appet diag-
Arcuate neurons can sense gluc and FA. Horm and R targs cent obesity. MC4R too widespread?
-leptin- on/on mouse 94. Posit cloning show LoF mut in leptin gene- trach Inher using in chrom markers. Sim LoF muts in hums rare. Resp to leptin infec. Little eff on comm obese- leptin resis. Leptin induc UCP exp=energ as heat.
LO3: disc metab synd and conseqs.
-synd= grp recog symp/abn Indic partic trait/dis.
Metab synd= clust of abn dang RFs assoc with CVD: abdo obes, HTN, insulin resis, high fast gluc, dyslipidaemia (decr HDL and incr TAG). Combin= ser health risk. Atherogenic. 20-25% ads. Over 40% of over 40’s. Prev incr over 60% last decade. Rates diff with sex and ethnicity. Comb sedent lifest.
-WHO criteria- waist:hip over 0.9 man, 0.85 wom. And/or BMI over 30. BP over 140/90. TAG over 1.7. HDL under 0.9. BM 7.8 2hr at least fast.
-int diab fed defin-
Cent obes (waist circ dep on ethnicity) and any 2 of:
TAG over 1.7mM or on tx for it. HDL under 1.03 male or 1.29 fem or tx. BP over 130/85 or tx. Fast BM over 5.6 or T2DM.
Metab synd in 80% T2DM. It=5x risk T2DM. 3x HD. Incr prev.
-aetiol- exact cause unkn. Insulin resis and cent obes sig RFs. Insulin resis- cells decr sensit and event resis-sig paths downstr of R. High plasma gluc= incr insulin but want decr BM= beta cells wear out and stop sec. Event hyperg=T2DM. Sig vasc dam even bef DM by glycation.
Cent obes- HTN, high chol, high BM, incr risk T2DM and CHD. Abdo fat more Indic than BMI. Over 1.7bn at risk globally. S Asians more cent obes than eur who have more than Afro caribb. Cent fat strng assoc insulin resis.
-prim interven- lifest. Calorie restric 5-10% mass loss 1yr. Mod incr phys activ. Healthy diet.
Secondary- if high risk may req drug. Statins decr LDL. AntiHTN eg ACE inhib. AntiDM.
LO4: expl dev origins health and dis theory in rel to epigenetics. Dev ori of ad health and dis.
-91 barker hyp- sev health surveys for dis markers, large male cohort. Stat strongest assoc btw ad dis incid and birth weight. U shape. Metab synd, CHD, stroke, HTN, T2DM.
Was rep eg Dutch famine 1944. Wom exposed early preg= kid lower birth weight and incr risk kid DM, obes, CVD as ad than kid born bef/after. Simil findings eg Nigerian civil war famine and China famine. Also chronic conds rel to placental weight.
-epigenetics though role in pass info over just one gen. Anoth lay contr how genes exp. epigenet mechs aff by- dev, env chem, drugs, aging, diet.
DNA meth comm, patt inherited so traits determ by it Inher. Met=activ/repress. Dutch famine kids met prom IGF2. Histone modif- bind epigenet facs to histone tails (P/met) atts ext of DNA wrap and avail of genes to be activ- accessib.
An epigenet trait is a stably Inher phenot res from changes in chrom w/o alt DNA seq.
-thrifty phenot hyp and fetal prog- low nutr dur preg= prog kid for simil conds. Metab set for low nutr, if then have plenty=inapp= obes, DM, metab synd etc.
Prog apps to inv insulin and Leptin resis to optim offspring surv in harsh env. Evol fav BUT high calorie low exerc life bad. Big prob in dev countries eg India DM. Simil changes occ after excess nutr intake dur preg.
Prog inv switch on/off genes at crucial times fetal dev. Emb/neonate nutr imbal= horm change, metab change, alt cell diff= epigenet regul eg histone modif, small nc RNA model gene exp, can bind mRNA and init deg= LT effs on gene exp as expec poor nutr= incr dis risk.
LO1: desc and outl contr of appet
-satiety cent in hypoth contr timing and amnt food intake. Lot horms and sensing int in appet contr.
Hypoth cont sev nuclei. SON prod OT, PVN ADH, SCN, arcuate nuc role in appet contr. At base hypoth so sense constit in blood eg FA and horm. Other brain areas also includes. Secondary neurons other areas hypoth get inp from prim arcuate neurons and coord resp via vagus nerve.
Prim arcuate neurons- excitat (orexigenic) stim appet via rel NPY and agouti rel pep. Inhib (anorexigenic) supp appet by rel POMC prohorm cleaved to beta endorphin, ACTH, aMSH. AMSH act on melanocortin 4Rs. (Diag).
Stom full= POMC rel= decr appet. Also beta end= tired and happy.
