Lecture 27: Metabolic Integration: Health and Disease Flashcards
thrifty gene hypothesis
ppl genetically program to store fat in times of plentiful food
leptin
nrg metabolism
neuro control of eating behavior
genetics… and weigh
40%-70% of weight due to genetics
Energy balance
amount of food consuming=amount of calories spending
can be in nrg balance and be unhealthy
all this means is that your weight is staying the same
positive energy balance
consume more cals than spending
weight gain
negative energy balance
consume fewer cals than spending
weight los
but you eventually have to reach nrg balance
canditate Thrifty genes
over active acetyl CoA
inc sensitivity to insulin
NOT inc levels of UCP
Why over active acetyl CoA
acetyl CoA carboxylase catalyzes commitment step for FA synth
Why inc sensitivity to insulin
inc metabolic flux through glycolysis, glycogen synth, triacylglycerol synth
why NOT inc levels of UCP
this would cause you to burn nrg and lose weight
Pima Indians… name 2 factors that likely differ between the lifestyles of these genetically similar population
diet
activity
Leptin as a “fat-o-Stat”
helps maintain set point weight
leptin is made by adipocytes
so more fat/fat cells= more leptin
this causes you to want to eat less and be more ative
How could you avoid gaining back weight lost by excercising?
eat less!
Why is it easier to lose weight quickly than weight gained slowly over time
gradual change causes set point to also gradually reset
long term positive nrg imbalance leads to leptin resistance through changes in leptin receptor signaling
leptin and obesity treatment
having mutations in leptin is rare, it would work for those people
IT WOULD NOT work for people who have high levels of leptin but are leptin resistant (like insulin resistant)
leptin production…
proportional to fat stores
more fat=more leptin
less fat=less leptin
Why does it make sense that leptin and insulin have the same effect on neuronal signaling>
lots of insulin=lots of glucose in blood
lots of leptin=lots of fat
based on the function and localized secretion of ghrelin and PYY, why is it good advice to eat slowly if you are trying to lose weight?
timing: it takes time for food to go from stomach to colon
ghrelin=EAT MORE
PYY336= don’t eat more
but we have to get from grhelin to PYY
Type 1 diabetes
DONT synth insulin
insulin sensitive
lack pancreatic beta cells
Type 2 diabetes
synth insulin
insulin RESISTANT
Brain interpretation of hormonal signals:
Eat less or more?
leptin signal in adipose=eat less, metabolize more
grehlin signal in stomach=eat more (rises during empty stomach)
PYY336 signal in colon: rises after meal, blocks eat more pathway
insulin signal in pancreas=eat less
Serum glucose levels
drink: blood sugar levels rise response to insulin shot: normal: blood glucose drops type 1: blood glucose drops type 2: levels don't respond to insulin shot
possible cause of diabesity
we have insulin, but body can’t respond
HOW???
response is WRONG
- elevated free fatty acids in serum, they are in membrane
- fatty acids lead to kinase activity
-kinase phosphorylates IRS protein, WRONGLY (phoshorys serine, not tyrosine)
-insulin receptor can’t phosphorylate the tyrosine
LOST IRS activity!!!
norma insulin signaling and glucose uptake
something binds outside
response inside
Tyr-P on IRS –> activation of PI-3k pathway–> glucose uptake!
So… on a larger scale, what causes diabesity???
ENVIRONMENTAL CONDITIONS!
this is NOT a genetic mutation
treat w/ diet and excercise
why do diabetics who are treated with TZDs see a drop in blood glucose levels but also weight gain?
dec in circulating fatty acids result in normal insulin signaling and glucose uptake
bad fat
not b/c more cals!
High LDL lelvels make it bad
how would the function of PPAR signaling proteins explain this observation?
PPAR are transcription factors
they are stimed by good fats
if a fat can stimulate PPAR, it may be better
What do PPARs do?
control adipocyte diff and lipid synth in adipose tissues
What does PPAR Gamma do
also regulates insulin sensitivity and lipid synth in liver cells
PPAR gamma and TZDs
TZDs inc insulin sensitivity by activating PPAR gamma genes
stimulant molecs
works like epi, mobalize and use lots of nrg
orlistat
inhibits pancreatic lipase
decs fat absorption
olestra
tastes like fat
but we don’t have the enzymes to digest it
