adipocytes and energy balance Flashcards

1
Q

what are the differences between the two types of adipocytes?

A

brown adipose tissue (BAT) specializes in oxidizing FA for heat production - does so with mitochondrial uncoupling protein
white adipose tissue (WAT) stores energy as TG

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2
Q

from where does WAT receive its FA? what must it do to acquire the FA?

A

from lipoprotein particles
must hydrolyze the FA to TG in the lipoprotein to absorb it
uses LPL to do so

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3
Q

how does WAT use glucose? How does it attain glucose?

A

glucose enters WAT through GLUT4 channels

WAT makes glycerol-3-phosphate, which is used to make TG

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4
Q

in what form does WAT store TG?

A

as a lipid droplet in the cytoplasm

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5
Q

how does WAT release FA from TG?

A

using lipases, including ATGL and HSL

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6
Q

how does insulin affect storage and release of FA in WAT?

A

1: increases LPL production in WAT and increases LPL transport to blood vessel surface
2: increases amount of GLUT4 on the plasma membrane
3: decreases ATGL and HSL activity
4: decreases perilipin phosphorylation => decreased HSL access to lipid droplet

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7
Q

brown adipocyte (summary card)

A

1: many small lipid droplets
2: high oxidative capacity (lots of mitochondria)
3: fatty acid oxidation uncoupled from ATP production due ot high expression of an uncoupling protein (UCP) in mitochondrial membrane => leakage of proton gradient
4: uncoupling is used for heat generation
5: for humans, mainly in infant
6: amount of BAT inversely correlated with obesity, induced by exercise and cold temperature => growing evidence that BAT is important in adults too

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8
Q

how do the lipid droplets in BAT compare with those in WAT?

A

BAT has many small lipid droplets, whereas WAT has on large droplet

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9
Q

how does the oxidative capacity of BAT compare with that of WAT?

A

BAT has high oxidative capacity, whereas WAT has low oxidative capacity

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10
Q

what does uncoupling protein do? what type of cells is it found in? why is it important to that cell type’s function?

A

uncoupling protein (UPC) is in the mitochondrial inner membrane of BAT cells
it allows FA oxidation in these cells to be separated from ATP production
this allows for the BAT cells to generate heat

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11
Q

what is the job of BAT?

A

generate heat

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12
Q

what is the job of WAT?

A

store and release FA for energy

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13
Q

what evidence has been found for an important role of BAT in adults?

A

induced by exercise and cold temperatures

levels are inversely correlated with obesity

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14
Q

in what age group is BAT usually found?

A

in infants

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15
Q

what type of WAT causes more risk of obesity-associated problems?

A

visceral WAT fat (belly fat) causes more risk than peripheral WAT fat (legs, buttocks, arms)

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16
Q

what are the sources of TG for human adipocytes?

A

chylomicrons - from intestines - carry dietary fat

VLDL - from liver - synthesized during times of excess dietary glucose

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17
Q

how if FA taken into adipose cells?

A

like in muscle, FA must by hydrolyzed from TG by LPL on the surface of blood vessel endothelial cells before uptake

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18
Q

what governs FA uptake in adipose cells?

A

concentration gradients
in anabolic state, ratio of FA outside:inside is high due to:
1: increased LPL activity (creates source outside adipocyte)
2: increased TG synthesis in the cells (creating a FA sink)

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19
Q

what happens to FA once it’s been taken up into a cell? what are the steps of this process?

A

FA is esterified onto glycerol backbone (converted back into TG)

1: FA converted to acyl CoA by fatty acyl CoA ligase
2: glucose enters into adipocyte through GLUT4
3: glucose converted to glycerol-3-phosphate
4: fatty acyl-CoA coupled onto glycerol-3-phosphate => phosphatidic acid
5: phosphatidic acid is dephosphorylated => diacylglycerol
6: final esterification of a third acyl-CoA onto diacylglycerol

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20
Q

what are the steps in making glycerol-3-phosphate from glucose in adipose tissue?

A

1: glucose taken into cell by GLUT4
2: glycolyzed to dihydroxyacetone phosphate (DHAP)
3: DHAP converted to glycerol-3-phosphate

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21
Q

what are the enzymes involved in lipolysis? what factors regulate each enzyme? (summary card)

A

1: ATGL (adipocyte triglyceride lipase) positioning on lipid droplet is induced by insulin
2: hormone-sensitive lipase (HSL) - activated by PKA-dependent phosphorylation - adrenaline activates, insulin inhibits
positioning of HSL on the lipid droplet is also regulated
3: monoglyceride lipase - doesn’t appear to be any regulation we need to know
4: perilipin - surronds lipid droplet - PKA-dependent phosphorylation creates conformational change => movement
adrenaline allows phosphorylation, insulin inhibits

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22
Q

what factors regulate ATGL? what do they do?

A

insulin and its counter-stimulatory hormone regulate by unknown mechanism, but they both control the positioning of the enzyme on the lipid droplet

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23
Q

what factors regulate HSL?

A

activated by PKA dependent phosphorylation
adrenaline activates
insulin inhibits
it’s positioning on the lipid droplet is also regulated

24
Q

where is perilipin found? how is it involved in lipolysis?

A

surrounds lipid droplet, blocking access to the lipid
must be phosphorylated => conformational change => moves out of the way so ATGL and HSL can access lipid
adrenaline stimulates phosphorylation
insulin inhibits

25
Q

what happens to FA produced by lipolysis in adipose cells?

A

diffuses out of the adipocyte and into the blood stream, bound to albumin

26
Q

what happens to the glycerol generated by lipolysis in adipose cells?

A

leaves cell through aquaporin-7 channels

goes to liver to undergo gluconeogenesis => glycerol

27
Q

what are the general rules of short-term energy balance? (summary card)

A

1: insulin activates energy storage mechanisms
2: a major metabolic focus of the body is to keep blood glucose levels uniform - does so largely through insulin
3: plasma glucose levels must be maintained to supply fuel for the brain
4: the effects of blood glucose levels drive many short-term aspects of energy balance through insulin
5: plasma FA level fluctuates more widely than glucose levels and is inversely related to insulin levels - due to effects of insulin on adipocytes, liver, muscle
6: excess dietary AA are not stored, but converted to glucose via gluconeogenesis or FA via lipogenesis - muscle can burn AA for fuel

28
Q

what is the relationship between plasma insulin levels and plasma FA levels?

A

plasma FA levels are inversely related to plasma insulin levels

29
Q

what are normal levels and ranges of glucose and FA in the blood?

A

glucose is maintained at a uniform level of about 90 mg/dL

FA levels fluctuate widely from 0.1-2 mM

30
Q

what happens to excess dietary AA?

A

they are not stored
converted to glucose via gluconeogenesis
converted to FA via lipogenesis

31
Q

why is regulation of plasma glucose levels so important?

A

plasma glucose supplies fuel for the brain

as a result, a major metabolic focus of the body is to keep blood glucose levels uniform

32
Q

post-absorptive state (before breakfast) (summary card)

A

1: low GLUT4 on plasma membrane of adipocytes, muscle - low glucose uptake
2: liver glycogenolysis and gluconeogenesis are relatively active to supply blood glucose
3: increase in adipocyte HSL activity, increasing FA release to blood. muscle is using much of this
4: low acetyl-coa carboxylase activity in liver
5: liver lipogenesis is low to conserve glucose
6: ACC activity in liver, muscle, and adipose is low => low malonyl CoA => higher carnitine acyltransferase activity => increased FA oxidation in liver and muscle
7: low ACC activity in liver => low FA synthesis

overall, FA oxidation is favored!

33
Q

what are insulin levels during preabsorptrive state (before breakfast)?

A

insulin levels are low due to requirement to maintain blood glucose

33
Q

what is glucose uptake like during preabsorptrive state (before breakfast)? how is this controlled?

A

glucose uptake is low

due to low GLUT4 on plasma membrane of adipocytes and muscle

34
Q

what happens with adipocyte HSL levels during preabsorptrive state (before breakfast)?

A

HSL levels increase => increased FA in blood

muscle uses much of this FA

35
Q

what happens to liver lipogenesis levels during preabsorptrive state (before breakfast)? what is the goal of this?

A

low to conserve glucose

35
Q

what happens to ACC activity levels in liver, muscle and adipose tissue during preabsorptrive state (before breakfast)? what is the result of this?

A

low activity => low malonyl-CoA => hihger carnitine acytltransferase activity => increased FA oxidation in liver and muscle
in liver, low ACC activity also means low FA synthesis

36
Q

what type of energy utilization is favored during preabsorptrive state (before breakfast)?

A

FA oxidation

37
Q

responses to food intake (summary card)

A

insulin levels rise and reverse all processes that were active during pre-food intake - glucose oxidation is now favored
so:
GLUT4 inserted into plasma membrane to allow for glucose uptake
HSL activity decreased, decreasing FA release to blood
ACC activity increases, resulting in decreased FA oxidation and synthesis

37
Q

what form of energy utilization is preferred after food intake?

A

glucose oxidation

38
Q

why does fat get into the circulation more slowly than sugars/proteins? (summary card sort of)

A

sugars leave intestine via hepatic portal vein - liver gets first shot at glucose and AA since this passes through the liver first - since pancreatic vein also empties into portal vein, liver gets insulin first too => takes only minutes for response to ingested glucose

FA leave intestine via chylomicrons through lacteals to thoracic duct - discharges into large veins of neck => heart is first organ newly ingested fat passes through - this process can take hours

this time lag is needed because it takes time for insulin to prepare adipocytes for the fat increase - insulin activates aspects of LPL production and since these are transcriptional changes they take time

39
Q

what is the path of sugars and proteins from the small intestine?

A

into hepatic portal vein –> liver => liver gets first shot at AA and glucose

40
Q

what is the path of insulin from the pancreas?

A

pancreatic vein –> hepatic portal vein –> liver

liver gets newly secreted insulin first

40
Q

how fast is the response to ingested glucose?

A

fast since transport from the small intestine to the liver is rapid

40
Q

what is the path of FA from the small intestine?

A

broken down and packaged into chylomicrons –> lacteals –> lymphatic system –> large veins of neck –> heart
as a result, heart is first organ fat passes through

41
Q

how long does ingested fat take to get into the bloodstream?

A

hours

41
Q

how does insulin prepare adipocytes for digested fats?

A

insulin activates several aspectes of LPL production, including transcription, protein processing, and transport to the endothelial membrane

42
Q

how long does it take for insulin to prepare adipocytes for digested fats?

A

since the changes to adipocytes are transcriptional, it can take hours

42
Q

what is basal metabolic rate (BMR)? when is it measured?

A

the amount of energy it takes to keep your cells and organs going
measured in the morning (post-absorptive, no breakfast) on an awake but sedentary individual (sleeping metabolic rate is slower than BMR)

43
Q

what is BMR proportional to?

A

highly proportional to non-fat body mass

43
Q

what percentage of the body mass is made up by skeletal muscle and how does skeletal muscle’s energy needs compare to those of other tissues?

A

most abundant tissue - makes up 30-40% of body mass

requires the most energy of all tissues, even at BMR

44
Q

which organs use a lot of energy per unit weight?

A

brain, liver, kidney

44
Q

how much energy does the heart use at BMR?

A

even at BMR, it’s still pumping at a rate of greater than once per second, so still uses appreciable amount of energy

45
Q

how much energy does adipose tissue use in comparison with other body tissues?

A

very little - 3-fold less than muscle

45
Q

how much total body energy does muscle use during exercise?

A

as much as 40% during intense aerobic exercise

46
Q

how much energy does it take to process food?

A

the processes of digestion, transport, and storage of excess energy use a lot of energy

46
Q

what do UCPs do the mitochondrial protein gradient?

A

dissipate it with out generating ATP