PCP NST

Question 1

What is the hypothesis for the point and the counterpoint?

Answer 1

Point: NST during cold exposure is seen in tissue other than BAT

Counter Point: NST during cold exposure is not found in tissues other than BAT

Question 2

Evidence for the point hypothesis (NST during cold is seen in tissue other than BAT)?

Answer 2

1. NST has been seen in a type of WAT made of brite or beige cells. Brite cells express UPC1 in their mta, which is the main factor that stimulates NST. No difference in the amount of UPC1 or respiration rates between brite cells and BAT. Wu et al. found UPC1 was highly expressed in brite cells when cold exposed, and show respiration rates close to BAT, leading to NST. Also, this study found that cold exposure was able to stimulate transdifferentiation of brite cells with high UPC1 in brown adipose deposits, which are big centres of NST. This further shows the contribution of brite cells in NST.
2. Skeletal muscle also seen to contribute in NST during cold exposure. One study showed that with long periods of cold exposure, UPC3 proteins in the mta of skeletal muscle cells were seen to contribute towards NST. They also found that with cold exposure was an increase in total daily EE, along w/an inc in stage 4 respiration in skeletal muscle (oxygen consumed w/out production of ATP). This indicates that cold exposure in skeletal muscle is able to activate UPC3, which then uncouples the mta from ATP production, leading to NST.
3. One study showed that triiodothyronine (T3) hormone in skeletal muscle has also been seen to induce NST in skeletal muscle by stimulating mta uncoupling from ATP production and increasing flux of citric acid cycle (inc glucose usage). This indicates that the energy from glucose is converted to energy in NST.

Question 3

Evidence for the counterpoint hypothesis (NST during cold is only seen in tissue other than BAT)?

Answer 3

There are 3 main points supporting the CP hypothesis that only BAT is responsible for NST during cold exposure:

1. If the thermogenic activity of BAT is inhibited, animals rely more on shivering as a mechanism for heat production. This is supported by a study that found UCP1 knockout mice continued to shiver in prolonged cold, whereas mice expressing UCP1 in BAT stopped shivering after some time. UCP1 is specific to BAT. If NST occurs in tissues other than BAT, we would expect mice to rely on heat production via other tissues rather than continuing to shiver. This also suggests that without the uncoupling activity of UCP1 in BAT, no other mechanism for heat production is sufficient
   to reduce the need for shivering.
2. The second point concerns the relationship between cold exposure and BAT metabolism relative to other tissues. When examining BAT rate of glucose uptake under cold conditions, one study demonstrated an inc in both the AMT of FDG (fluorodeoxyglucose) being taken up by BAT as well as the RECRUITMENT of more BAT. This suggests a correlation of BAT activity and recruitment with NST in cold conditions. Also, prolonged cold exposure increases the metabolic activity of BAT relative to the deltoid, trapezius, and subcutaneous adipose tissue. Although the longus colli muscle shows increased glucose uptake as well, only BAT shows a significant cold-induced inc in oxidative metabolism, suggesting the longus colli muscle increases glucose uptake for nonoxidative metabolism. So, when looking at NST in terms of mtal uncoupling, BAT shows significantly more NST than these other tissues examined in their study
3. The third point concerns changes in BF to BAT relative to other tissues during cold exposure. A BF study demonstrated that, on cold exposure, there’s a large inc in BF to BAT and not to skeletal muscle in cold acclimated mice. Blood leaving BAT was also depleted in oxygen, which indicates increased oxygen consumption, metabolism, and heat production. These increases in BF and oxygen consumption might be required for increased BAT metabolism and proliferation in the cold. If NST occurs in other tissues such as skeletal muscle, we would have expected greater increase to those tissues.