hormonal control of metabolism II Flashcards
why is hormonal control of metabolism needed?
needed to keep fuel intake and energy expenditure in balance so an appropriate amount of adipose tissue in maintained
what happens when hormonal signals that control metabolism fail + you eat/drink more calories than you need? (2)
you convert the excess fuel into TAGs and store them in adipocytes, and you divert the excess fuel to heat production
which class of hormones are released from adipose tissue
adipokines
what type of hormones are adipokines
peptide hormones
role of adipokines?
they inform other tissues of the adequacy of TAG energy reserved to balance fat synthesis and oxidation
what was the first adipokine discovered
leptin
where in the body is leptin located
adipose tissue (bc it’s an adipokine)
when is leptin secreted from adipose
when TAG stores are sufficient to curtail appetite and increase energy expenditure (you have enough TAGs = stop eating)
list 3 things that may occur in the leptin knockout method (this was done in mice experiments)
high cortisol, unrestrained appetite, can’t stay warm
where does leptin secreted from adipocytes go
goes into the blood and to the hypothalamus
what happens when leptin reaches the hypothalamus
hypothalamus has leptin receptors, and it activates a neuronal response that returns back to adipocytes
after leptin binds to the hypothalamus and it sends it’s signal back to adipocytes, which neurotransmitter do the adipocytes release
norepinephrine
what happens once adipocytes secrete norepinephrine
norepinephrine activates a GPCR pathway to adenylyl cyclase, which increases cAMP levels and activates PKA
after norepinephrine release has led to PKA activation, what does PKA do (2)
activates mobilization of lipid droplets + activates the expression of the uncoupling protein (UCP1) in brown adipose tissue
expression of which uncoupling protein is activated by PKA
UCP1
where is UCP1 activated
brown adipose tissue
purpose of BAT
common in newborns/hibernating animals to keep vital organs warm
T or F: there is much less BAT in adults
true
how can BAT synthesis be activated in adults
via significant cold exposure
describe the structure of WAT (composition + shape)
contains one large lipid droplet, spherical
describe the structure of BAT (composition + shape)
smaller, contains multiple lipid droplets, polygonal, contain many more mitochondria, surrounded by a denser capillary network
which type of adipose is spherical
WAT
which type of adipose is polygonal
BAT
which type of adipose contains multiple lipid droplets
BAT
which type of adipose contains a single lipid droplet
WAT
what is another name for the uncoupling protein UCP1
thermogenin
describe what NORMALLY happens to protons after the formation of the proton gradient from the ETC
the protons would normally flow back into the matrix through ATP synthase to generate ATP
describe what happens to protons from the proton gradient of the ETC when thermogenin (uncoupling protein) is present
thermogenin forms a channel in the IMM to allow protons to flow back in WITHOUT generating ATP. Allows dissipation of the H+ gradient without building ATP = energy released as heat
T or F: thermogenin allows lots of ATP production
false; no ATP is made, and instead the energy formed is released as heat
which adipokine is secreted from adipocytes in a prolonged fast
adiponectin
briefly, what does adiponectin do (ie which general processes does it upregulate and downregulate)
upregulates energy-producing processes and downregulates energy-consuming processes
specifically, which processes does adiponectin upregulate/increase
uptake of FAs from blood into myocytes, rate of b-ox in myocytes, increases appetite
specifically, which processes does adiponectin block/inhibit
blocks FA synthesis, cholesterol synthesis, and GNG. Inhibits thermogenesis
what is a myocyte
muscle cell
which enzyme does adiponectin stimulate
AMP-activated protein kinase (AMPK)
describe the energy levels that are present when AMPK is activated by adiponectin
low energy levels
which molecule activates AMPK during low energy levels
AMP
which molecule inhibits AMPK during high energy levels
ATP
list 6 target tissues of AMPK
heart, skeletal muscle, brain, pancreas, liver, adipose
list 4 target enzymes of AMPK
GLUT4, HSL, FASI, ACC
how does AMPK activate/inactivate target enzymes
via phosphorylation
AMPK role in individual cells?
monitors nutrient status and can shift metabolism towards energy generation
AMPK role in hypothalamus?
monitoring nutrient status across the entire organism through bottom-up pathways
what is ghrelin
an appetite stimulant
where in the body is ghrelin found
stomach
list 4 molecules that all affect AMPK levels in the hypothalamus
ghrelin, leptin, adiponectin, insulin
which pathways in the hypothalamus are initiated to adjust feeding behaviors once AMPK levels have changed
top-down hormonal pathways
by how many years does diabetes reduce the lifespan
5-15
list 3 things that a person with diabetes is more likely to be hospitalized for
cardiovascular disease, renal disease, lower limb amputation
which type of diabetes is more common
type 2
what is happening in the body during type 1 diabetes
autoimmune response: immune system destroys pancreatic B cells
type 1 diabetes: when does it begin
childhood
type 1 diabetes: treatment?
daily insulin injections, life-long management of dietary intakes and activity levels
type 1 diabetes: preventable?
very hard to prevent this type
type 1 diabetes: severity of symptoms?
quickly become severe and life threatening
type 2 diabetes: what’s happening in the body
insulin is produced by the body develops resistance
type 2 diabetes: when does it start
adulthood
type 2 diabetes: severity of symptoms?
milder at first but organs accumulate damage over time
type 2 diabetes: typical weight of patients?
obese
what is the third type of diabetes
gestational
gestational diabetes occurs in -% of pregnant women
3-20%
gestational diabetes: what’s happening in the body (of the mother)
hormonal changes = mom can’t produce enough insulin
gestational diabetes: result to the mother?
increased risk of type II diabetes later in life
gestational diabetes: result to the fetus?
can cause still births, pre-term labour, larger babies (= increased likelihood of birth injuries). Large babies = at higher risk of respiratory distress, obesity, and type 2 diabetes
how was the cause of diabetes discovered in dogs
scientists removed pancreas from dogs –> they then drank lots of water, produced more urine, and urine had high glucose levels. Dogs eventually died
before the discovery of insulin, what was the treatment for diabetes
prolonged + severe calorie restriction to keep blood glucose levels low
describe the experiment that lead to insulin discovery (+ name the two scientists)
Banting and MacLeod purified a pancreas extract from B cells (was first tested on dogs, then humans). Human version was more purified. Extract = named insulin
what does the lipid toxicity theory suggest
suggests at how obesity contributes to insulin resistance
lipid toxicity: describe what happens to adipocytes as an individual gains weight
adipocytes become larger as more TAGs are stored there. Eventually the adipocytes are completely filled with TAGs and can no longer accept any more
lipid toxicity: what protein do TAG-filled adipocytes release
MCP-1
lipid toxicity: what does MCP-1 do
attracts macrophages to adipocytes
lipid toxicity: what do the macrophages do to adipocytes
they enter, trigger inflammatory response
lipid toxicity: after macrophages initiate the inflammatory response in adipocytes, what is released
the inflammatory cytokine TNFa
lipid toxicity: name the inflammatory cytokine that is released
TNFa
lipid toxicity: what does TNFa do
promotes the release of FFAs into the blood
lipid toxicity: after TNFa promotes FFA release into the blood, what occurs
FFAs travel through the blood to the muscle, where they accumulate as lipid droplets
lipid toxicity: what is the affect of FFAs accumulating as lipid droplets in the muslce
lipid droplets in the muscle inhibit the movement of GLUT4 to the PM –> insulin insensitivity
lipid toxicity: how is adiponectin synthesis affected by insulin resistance
adiponectin synthesis is reduced
lipid toxicity: impact of less adiponectin?
lower FA ox and higher FA synthesis
lipid toxicity: what type of feedback does this pathway use
positive feedback loop (bad)
lipid toxicity: describe how this uses a positive feedback loop
excess lipids lead to insulin resistance, insulin resistance leads you to lower adiponectin = higher FA synthesis = even more lipids
