Thermogenic Fat Flashcards
Brown Fat
- adipose depot located in the interscapular region
-The mitochondria brown is due to all the iron in the mitochondria - These mitochondria utilize glucose and free fatty acids to generate heat, not ATP
- Multiple lipid droplets
- Highly vascularized and innervated (nerves in her because)
What does Brown fat do?
- Responds to decreases in ambient temperature
- Uncouples the electron transport chain to generate heat rather than chemical energy
- Mobilizes lipids to be catabolized - substrate for heat
How does Brown fat Uncouple the electron transport chain?
- Specialized protein: uncoupling protein 1 (UCP1)
- Creates a pore in the mitochondrial membrane thereby collapsing the electron gradient- the movement of protons creates heats
- Results: Cold blood moving through the blood vessels, that brown fats warms the blood
Why is brown fat important to mammals?
- Hibernation:
- Neonatal warmth
- Adaptive thermogenesis - nonshivering
Hibernation
- Animals store large amounts of white fat
- Downregulate body temperature
- Depending on temp and daylight, animals are aroused
- Warmup body using brown adipose tissue to burn stored white fat, white fats also contribute
Neonatal Warmth:
- Small Surface area: detects changes in ambient temperature
- Higher metabolic rates
- Non-shivering thermogenesis
How is non-shivering thermogenesis activated?
- The skin has thermoreceptors that sense changes in temperature.
- It will send a signal to the hypothalamus
- The hypothalamus activates the sympathetic nervous system that produces norepinephrine
- NE targets the brown adipocyte and turns it on
- The brown adipocyte has Beta 3 Adrenergic Receptor
-Beta 3 Adrenergic Receptor: g coupled proteins that bind to norepinephrine
6 steps Non-shivering thermogenesis:
Step 1: Sympathetic nerve releases NE which binds to Beta3 receptors
Step 2: This turns on cAMP and activates protein kinase A
Step 3: Two effects: turn on UCP1 / mitochondrial biogenesis (more mitochondria). OR
Step 4: Protein kinase A turns on lipolysis, which causes lipid metabolism
Step 5: The lipid metabolism leads to the citric acid cycle and electron chain
Step 6: From the side effect of UCP1, it will make holes in the electron transport chain to generate heat instead of ATP
Beige Fat:
Subcutaneous fat has more of the beige fat
Beige fat was absent in cold temp
Difference from brown fat:
- Brown - has designated depots
- Brown, has different stem cells of origin
- Different genetic signatures
- Beige fat is cold generated (made) whereas brown fat is cold activated (turned on)
- Beige fat only forms in white adipose tissue
What’s common between brown and beige fat?
- Regulate adaptive thermogenesis: Core is UCP1
- Multiple lipid droplets- a more accessible way to liberate fatty acids for substrates
- Uncouple the electron transport chain to heat then ATP
Metabolic benefits of Brown Fat:
- Increase in BAT mass and activity
- Increase in Thermogenic Capacity
- Decrease in Body Fat content
However: Thermogenic fat decreases with body fat and BMI
Thermogenic fat decreases with age
Can thermogenic fat help obesity?
Maybe, BAT(brown adipose tissue) pushes heat ie expenditure side
DNP, like UCP-1 by allowing protons to move across the mitochondrial membrane
Though it increased metabolic rate it took all of the mitochondria and uncoupled it. NO ATP
Thermogenic fact activity increases expenditure, but it takes forever to burn fat and would need a lot of BAT to burn enough fat and a normal rate
Noncold methods”
- Beta 3 adrenergic receptor agonists are contraindicated, stimulate heart rate, and could give a heart Counter intuition if the person is taking beta blockers
- You would need a specific type of agonist but it is hard because of homology
- Found Mirabegron: used in patients with overactive bladder
