Reglation Of Body Weight

Question 1

Leptin

Answer 1

Lep thin = satiety

= body weight focused

=adipose shrinking / growing modifies level of leptin

Produced by adipose tissues

Question 2

Ob/ob

Answer 2

Obese
Deficient in ligand leptin
Always hungry
Insulin resistant
High blood glucose bc can’t stop eating

Question 3

Db/db

Answer 3

Diabetic
Obese
Lacks receptor for leptin

Question 4

Primary location of leptin receptor

Answer 4

Hypothalamus

• neurons of arcuate nucleus

Question 5

What regulates ampk?

Answer 5

Ratio of amp to atp

Leptin

Adiponcerin

Question 6

Ucp1 direction of H+

Answer 6

Into matrix

Question 7

Organism level hormones for E balance

Answer 7

Leptin = energy use

Insulin = energy storage

Question 8

Cellular level E balance regulation

Answer 8

Amp/atp to AMPK

FA derivatives to PPARs

Question 9

Pathway for leptin

Answer 9

Leptin from adipose to hypothalamus

Hypothalamus releases Norepinephrine = fight or flight = GLPC protein called B3AR

= g alpha activated - AC - cAMP increases

PKA activated
= MAPCK activated
= ucp1 transcription goes up

Also pka = periliptin phosphorylated = lipases can breakdown TAGs = FFAs to mitochondria

= UCP1 gene enables oxidation of atp via thermogenesis = no atp released, heat instead

Want to get rid of body energy as heat

Want to break down fat = size of adipose to be maintained

Question 10

Signals from neuron that have info about hunger

Answer 10

NPY = eat = neuropeptide Y

Alpha - MSH = don’t eat

Question 11

Leptin —> neuron signals

Answer 11

Inhibits NPY

Activates alpha MSH

Question 12

Insulin —> neuron signal

Answer 12

Inactivated NPY

Insulin is from pancreas

Question 13

GLP1 —> neuron signal

Answer 13

Inactivates NPY

From gut

Question 14

Ghrelin

Answer 14

Activates NPY

From Stomach

Question 15

Adiponectin

Answer 15

From adipose tissue

Increases sensitivity to insulin

Activates FA uptake and rate of beta oxidation

Can activate AMPK ?

Question 16

Adenylate kinase reaction

Answer 16

ATP + AMP —> 2ADP

Amp activates AMPK

ATP inactivates ampk

Question 17

AMPK details

Answer 17

Key kinase protein

Activates catabolism processes = atp production

Inactivates anabolism = synthesis, transport, muscle contraction, growth

Question 18

Leptin interaction with ampk

Answer 18

In hypothalamus = ampk promotes feeding behavior = promotes atp production = limits atp consumption, increase other energy production

leptin inhibits ampk = appetite suppression by inactivating NYP and activating alpha MSG = we do not need to break things down
= we are fueled and we need to use the fuel to build things

This in turn decreases atp in tissues = amp:atp increases = eventual activation of ampk in peripheral tissues

In peripheral tissues : leptin leads to norep being releases = PKA pathways, TAG breakdown
== beta oxidation = no atp production = ratio is not improved for ampk

Question 19

Kinase for AMPK

Answer 19

LKB1
= liver kinase protein B

Question 20

What raises amp to atp ratio?

Answer 20

Chemical and physical work

ATP —> adp + pi = synthesis / motors

ATP —> amp + PPi = FA, amino acid activation

Question 21

What processes can totally mess up atp production?

Answer 21

Hypoxia, glucose starvation, certain poisons

Question 22

ACC and AMPK

Answer 22

ACC = acetyl coA Carboxylase = produces malonyl coa = first step to FAS
= liver/ white adipose tissue
-> malonyl coa inhibits carnitive Acyl transferase = 1st step to FA breakdown in mitochondria

AMPK inhibits ACC

Question 23

When you are hungry, body wants to

When you are full, body want to

Answer 23

Break down materials (for e)

Build materials (using e)

Question 24

Mechanisms of hormone action

Answer 24

G protein coupled receptor

Receptor enzyme = thyrosine kinase

Gated ion channel

Nuclear receptor

Question 25

PPAR details

Answer 25

Peroxisome proliferator activates receptors Act in liver, muscle, adipose tissues Respond to changes in dietary lipids Alter gene expression for fat/ carbs metabolism

Question 26

Ligands for PPARs

Answer 26

FAs and FA derivatives

Question 27

What enables PPAR to regulate rate of transcription for target genes?

Answer 27

Binds to its Ligand Now it is able to bind to RXR = heterodimer RXR has separate ligand = 9cisretinoic acid Binds to DNA regions of interest See vitamin d3 example and VDR later on

Question 28

PYY details

Answer 28

Acts on Same GPCR site as GLP1 - both from gut Glucagon like peptide receptor = all over the body = pancreas = gpcr patwhays - galpha for sure = PKA = calcium up and insulin secretion up = signal to inactivate NYP neuron = hunger down

Question 29

Glucagon signals what

Answer 29

Hormonal signal from pancreas alpha cells Blood glucose levels too low! Opposite effects of glucose in blood Need to release glucose Counters insulin effects = glucose uptake when blood sugar is high

Question 30

Through what pathway does glucagon send signals?

Answer 30

GPCR Specifically alpha protein = same as epinephrine = camp up so PKA up so glucose released = fight or flight = need energy fast = glucose in blood needed

Question 31

Is PKA not involved in insulin signaling?

Answer 31

No Only g protein signaling pathways Insulin = PI3K pathway = PKB involved MAPK pathway = raf1, mek, Erk involved

Question 32

Thiazolidine and PPARs

Answer 32

TZD is agonist for PPAR gamma Stimulates genes for insulin sensitivity Glucose uptake Glycogen synthesis

Question 33

Leptin receptor pathway

Answer 33

1 leptin molecule 2x receptor molecules Each with once JAK Autophosphorylate JAK = leptin receptor is phosphorylated Activated Phosphorylates STAT = 1 per JAK 2x STAT dimerize = genes for appetite control = POMC transcription

Question 34

POMC is precursor for

Answer 34

Alpha MSH

Question 35

Leptin pathway memory

Answer 35

Lip thin Get jacked stat = each arm needs to be buff = 2x Jak and stat