Brown Fat Flashcards
Description of brown fat
- Brown fat is a distinct type of fat
- Brown adipocytes are filled with iron-containing mitochondria
- Its biological role is to produce heat to help maintain body temperature (it is a metabolic tissue of high activity!)
- It was known to be present in newborns (and hibernating mammals) but initially thought to be absent in adults (know this is incorrect now)
- The hitherto-unexpected discovery that BAT was present in adults launched a new field of research i.e. therapeutic targeting of BAT for the treatment of obesity
Characteristics of WAT vs BAT
What is brite adipose tissue?
brite/ beige
* mix of brown/white
* white adipocytes that adapt brown phenotype (start burning energy)
What happens in the ETC with brown fat?
uncoupling of oxidative phosphorylation
* The uncoupling proteins bypass the protein pump that uses H+ to produce ATP and instead the UCPs bring the protons back which creates heat
What are the types of UCPs?
- UCP1: brown adipose tissue; good for producing heat and burning fat
- UCP2: beta cells; bad because when they are burnt out they express UCP2 which inhibits insulin secretion so just produces heat from the glucose
Brown fat is highly ??
inervated
* UCP1 means more uncoupling
* Pcg-1𝝰 regulated making of mito
What is used for BAT imaging in newborns?
Using FDG-PET (flourodeoxyglucose)
* can add image on to a CT scan
Brown/white fat imaging in adults
What is important from this?
Women express more BAT than men
What are some determinants of BAT?
BAT prevalence, mass, and activity is determined by
* less BAT in hotter temperature
* lose BAT with aging
* less BAT with higher BMI
* less BAT with higher glucose
what happens with BAT in colder temperatures?
BAT becomes more active, taking up more glucose
* further increased BAT activity after cold acclimation
Gene expression profiling of BAT vs. WAT
Seems to be 5 major brown fat genes expressed
* UCP1
* DIO2
* PGC1𝝰 (creates more mito)
* PRDM16
* ADRB3
How does BAT correlation with BMI?
BAT inversely correlates with BMI
* higher BMI = less BAT
* More fat = less BAT
* less BAT in diabetes (cause or a consequence?)
Mechanisms of aging-related
impairment of BAT function
Combination of
* mito dysfunction
* SNS
* endocrine balance
Results from retrospective study at MSKCC looking at BAT and metabolic health
- Assessed W vs M; Women express more BAT+
- BAT more prevalent when younger
- less BAT activity in the summer
- less BAT with increased BMI
- BAT most prevalent in supraclavicular (followed by cervical)
- Less BAT in T2D, dyslipidemia, atrial fibrialliation, CAD, CVD, CHF, hypertension
- more BAT with more HDL
- less BAT with more glucose
- LDL and total cholesterol has no effect
Where do brown adipocytes come from?
BAT comes from muscle
* Pax7 embryonic progenitors which then differentiate into either BAT or skeletal muscle
* molecular switch turned off or on respectively
Origins of BAT vs WAT cells
Both originate from mesenchymal stem cells but have different progenitors
What is beiging?
when white adipocytes acquire a brown-like phenotype
* TZD may contribute to beiging SAT?
What is thought to provoke the whitening of fat?
high fat diet
Effect of exercise of BAT production
Acute exercise induces Fndc5 expression (myokine/ adipokine) in the skeletal muscle and induces the browning of fat.
* Fndc5 is a membrane protein and with acute exercise it can shed increasing concentration in the plasma. This leads to the rise in irisin hormone which is the mediator to act on WAT to to stimulate UCP1 expression and browing of WAT.
* Irisin could play a role in energy homeostasis
Could a “fat burning” pill target brown fat?
Therapeutic strategies to treat obesity could involve stimulation of BAT or the browning of WAT (give them irisin for example)
* “BAT activation accounts for less than 20 kcal/day during moderate cold stress, even in subjects with relatively large BAT depots”
* Does not actually burn that much per day so only a small effect
Food ingredients that have been shown to activate brown fat
- Menthol
- Capsaicin and capsinoids
- Curcumin (turmeric)
- Tea catechin and caffeine
- Some polyphenols
- Fish-derived omega-3s
