Response to: Why Browning of White Adipocytes in Fat Grafts Correspond to Increased Inflammation

With great respect we would like to thank the authors of the letter¹ for their inspiring ideas and for the attention they have paid to our work. The comments in the letter mainly include the following: (1) a 0.5-mL fat graft volume is rarely used in the clinic and therefore the clinical transformation achieved is unclear; (2) the beige adipocytes present in fat grafts were regenerative components that could promote graft survival, with the 0.5-mL group possibly regenerating more than the 0.1-mL group; (3) further investigation is needed to explain the fact that the recipient site is in an extremely hypoxic state after fat grafting, whereas the beige adipocytes are in an exhausted state because of their elevated energy expenditure.

First of all, we have reported our clinical results in another article which revealed that browning of adipocytes also occurred in necrotic fat grafts in patients who received autologous fat grafting surgeries.² Furthermore, the purpose of applying 0.5 mL in our animal study was to establish it as the necrotic group in contrast to 0.1 mL nonnecrotic group, which was further confirmed through analysis of the necrotic marker cleaved caspase-3. Our results showed that browning of adipocytes was discovered only in the 0.5-mL group and not in the 0.1-mL group.³

Second, a previous study reported that beige adipocytes could be induced by cold, trauma, and other stimuli. Induced beige adipocytes were negative for BrdU and Ki67, indicating that there was restricted proliferation among newly formed beige adipose tissue.^4-6 In addition, beige and brown adipocytes were more prone to necrosis under oxidative stress, hypoxia, and inflammatory stress.^7,8 Combined with the results from our study that the formation of beige adipocytes was more evident in necrotic fat grafts in both humans and mice,^2,3 these studies taken together indicate that the regenerative ability of beige adipocytes is very limited, and they are barely able to survive extreme environments. Interestingly, a genetic lineage–tracing study revealed that cold-induced beige adipocytes could convert into mature white adipocytes after 5 weeks of warm adaptation.⁹ This study suggests that beige adipocytes are capable of reversing back to white adipocytes when the stimulus is withdrawn and the conditions are appropriate.

Therefore, we tend to presume that fat grafting is limited by oxygen delivery relative to oxygen metabolism. Beige fat can form in response to trauma and inflammation after fat grafting. Beige adipocytes have higher metabolic rates (and thus higher oxygen metabolism) than white fat. Although their higher metabolism might contribute to graft failure in some instances, beige adipocytes are in a reversible condition. Therefore, understanding this process might allow the development of an intervention to prevent conversion between white fat and beige fat, and thereby increase graft survival. The mechanism behind the physiology of beige adipocytes after fat grafting remains to be further investigated.

Disclosures

The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Funding

This work was supported and funded by Chinese Academy of Medical Sciences Initiative for Innovative Medicine (CAMS-12M) (2017-12M-3-006) and the Plastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences.

References