HRR: adipose tissue Flashcards
Describe the components of adipose tissue
A loose connective tissue consisting of adipocytes, resident M2 macrophages, vascular endothelial cells, T cells, and fibroblasts
What are the two types of adipose tissue
White and brown
What are the functions of white adipose tissue
To store energy and endocrine functioning
What is the main function of brown adipose tissue
Generate body heat
Which adipose tissue has more capillaries
Brown
What is the structure of white adipose tissue
Unilocular with large lipid droplets (1 per cell)
What is the structure of brown adipose tissue
Multilocular with many lipid droplets per cell
Where is white adipose tissue found
As subcutaneous and visceral fat in the intra-abdominal cavities
Where do we find brown adipose tissue
It is mostly found in infants, but in adults, it is cervical, supraclavicular, and paravertebral regions
Describe hypertrophy of adipocytes
Increased size of tissue due to lipogenesis or excess TG accumulation
Describe hyperplasia of adipocytes
Increase in the number of adipocytes due to adipogenesis via proliferation and differentiation
What can happen as with adipocyte hyperplasia in obesity
The adipocytes may start to undergo necrosis due to a lack of blood supply
What apolipoproteins do chylomicrons pick up in circulation
ApoCII and ApoE
Describe how adipose tissue gains FA from chylomicrons
ApoCII on the chylomicron interacts with LPL from the adipose tissue. This causes the ApoCII to signal breakdown of the TGs within the chylomicron, forming glycerol and FA. The FA will enter adipose tissue, and the glycerol and chylomicron remnants return to the liver
TG made in the liver is transported via…
VLDL
How do we get the glycerol backbone needed to resynthesis TG in adipose tissue
Glucose! Glucose is converted to G3P, which converts to glycerol and combines with FAcoA to form TG
What signals mobilization of stored TG
Glucagon and epinephrine
What is the secondary messenger used by glucagon and epinephrine to release FA from adipocytes
cAMP/PKA
What proteins in adipocytes are activated by PKA
Perilipin and hormone-sensitive lipase
Describe how glucagon/epinephrine lead to FA entering the blood
They bind to a G2 receptors on the surface of the adipocyte, leading to cAMP release and PKA activation. PKA activates hormone sensitive lipase and perilipin, leading to TG stored in the lipid droplet to convert to FA and enter the cytosol of the adipocyte. The FA then transfers into the bloodstream and is carried by albumin until it reaches its next destination for use
What are some consequences of elevated free fatty acids
- Inhibited glycogen synthesis
- Reduced insulin sensitivity
- Increases glycogenolysis even though it may not be needed
- May be involved in inflammatory processes that promote coronary artery disease
All of these may be a future predictor of T2DM
What can induce browning of white adipose tissue
A cold environment; it is an adaptive process
What transcription factors are involved in beiging of white adipose tissue
PPARy, PRDM16, EBF2, PGC1-a
What does UCP1 do
It uncouples the ETC from ATP synthase in brown adipocytes. It brings protons from the intermembrane space into the matrix, allowing the energy to be released as heat instead of using it to make ATP
What does UCP1 do to O2 consumption and oxidation of NADH
Increases both
How does adipose tissue serve as an endocrine function
Releases sex steroids, adipokines, and other hormones
What is leptin
Secreted by adipocytes and mediates/controls appetite. It may also act as an inflammatory cytokine and may decrease insulin secretion
What happens without leptin
We eat uncontrollably and gain weight
Why does leptin therapy not aid in diet-induced obesity
A lot of times, those who are obese secrete higher levels of leptin. As such, they may develop leptin resistance causing the brain to not properly receive the satiety signal
What is adiponectin
It plays a role in regulating blood glucose, lipid metabolism, and increases insulin sensitivity. It may decrease inflammation and apoptosis. This is kind of considered the good one.
What kind of tissue is adiponectin highest in
Lean tissue (subq fat); decreases as adiposity increases
Describe why we’d see TNF-a in adipose tissue
As adipocytes necrose, more M1 macrophages are recruited. These macrophages secrete high levels of TNF-a
Describe IL-6 in adipose tissue
It is secreted by the tissue and stimulates lipolysis/VLDL secretion, decreases adiponectin, and attenuates insulin sensitivity in the liver
What cytokine decreases adiponectin expression
IL-6
What is resistin
It is secreted by M1 macrophages recruited to adipose tissue that promotes inflammation and enhances insulin resistance and oxidative stress by increasing NFkB transcription
What is plasminogen activation inhibitor 1
It inhibits tissue plasminogen activator and urokinase, increasing clotting, atherosclerosis, insulin resistance. Increases risk of MI or stroke
Compare pathological features of subq and visceral fat
Subq fat does not tend to undergo necrosis in the way visceral fat does. Meaning it has resident M2 macrophages that release anti-inflammatory molecules like adiponectin. Visceral fat is more likely to undergo necrosis, causing the recruitment of M1 macrophages that release inflammatory adipokines and reduce secretion of anti-inflammatory adipokines. This may lead to syndromes like T2DM, CVD, and other metabolic issues.
What are the 3 mechanisms linking adiposity to insulin resistance
- FFAs inhibit glucose uptake and glycogen synthesis
- FFAs increase glycogenolysis
- TNFa signaling inhibits IRS proteins downstream of the insulin receptor
