White Adipose Tissue as a Site for Islet Transplantation

2020 ◽  
Vol 1 (1) ◽  
pp. 55-71
Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Shohta Kodama

Although islet transplantation is recognized as a useful cellular replacement therapy for severe diabetes, surgeons face difficulties in islet engraftment. The transplant site is a pivotal factor that influences the engraftment. Although the liver is the current representative site for clinical islet transplantation, it is not the best site because of limitations in immunity, inflammation, and hypoxia. White adipose tissue, including omentum, is recognized as a useful candidate site for islet transplantation. Its effectiveness has been evaluated in not only various basic and translational studies using small and large animals but also in some recent clinical trials. In this review, we attempt to shed light on the characteristics and usefulness of white adipose tissue as a transplant site for islets.

2020 ◽  
Vol 1 (2) ◽  
pp. 55-70
Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Shohta Kodama

Although islet transplantation is recognized as a useful cellular replacement therapy for severe diabetes, surgeons face difficulties in islet engraftment. The transplant site is a pivotal factor that influences the engraftment. Although the liver is the current representative site for clinical islet transplantation, it is not the best site because of limitations in immunity, inflammation, and hypoxia. White adipose tissue, including omentum, is recognized as a useful candidate site for islet transplantation. Its effectiveness has been evaluated in not only various basic and translational studies using small and large animals but also in some recent clinical trials. In this review, we attempt to shed light on the characteristics and usefulness of white adipose tissue as a transplant site for islets.


Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Shohta Kodama

In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.


2020 ◽  
Author(s):  
Fatemeh Rajaii ◽  
Dong Won Kim ◽  
Jianbo Pan ◽  
Nicholas R. Mahoney ◽  
Charles G. Eberhart ◽  
...  

AbstractRetrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure. We report that mouse retrobulbar fat is a neural crest-derived tissue histologically and transcriptionally resembles interscapular brown fat. In contrast, human retrobulbar fat closely resembles white adipose tissue. Retrobulbar fat is also brown in other rodents, which are typically housed at temperatures below thermoneutrality, but is white in larger animals. We show that retrobulbar fat in mice housed at thermoneutral temperature show reduced expression of the brown fat marker Ucp1, and histological properties intermediate between white and brown fat. We conclude that retrobulbar fat can potentially serve as a site of active thermogenesis, that this capability is both temperature and species-dependent, and that this may facilitate regulation of intraocular temperature.


2017 ◽  
Vol 37 (16) ◽  
Author(s):  
Shui-Rong Zhou ◽  
Liang Guo ◽  
Xu Wang ◽  
Yang Liu ◽  
Wan-Qiu Peng ◽  
...  

ABSTRACT White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT.


2020 ◽  
Vol 477 (6) ◽  
pp. 1061-1081 ◽  
Author(s):  
Greg L. McKie ◽  
David C. Wright

Our understanding of white adipose tissue (WAT) biochemistry has evolved over the last few decades and it is now clear that WAT is not simply a site of energy storage, but rather a pliable endocrine organ demonstrating dynamic responsiveness to the effects of aerobic exercise. Similar to its established effects in skeletal muscle, aerobic exercise induces many biochemical adaptations in WAT including mitochondrial biogenesis and browning. While past research has focused on the regulation of these biochemical processes, there has been renewed interest as of late given the potential of harnessing WAT mitochondrial biogenesis and browning to treat obesity and type II diabetes. Unfortunately, despite increasing evidence that innumerable factors, both exercise induced and pharmacological, can elicit these biochemical adaptations in WAT, the underlying mechanisms remain poorly defined. Here, we begin with a historical account of our understanding of WAT exercise biochemistry before presenting detailed evidence in favour of an up-to-date model by which aerobic exercise induces mitochondrial biogenesis and browning in WAT. Specifically, we discuss how aerobic exercise induces increases in WAT lipolysis and re-esterification and how this could be a trigger that activates the cellular energy sensor 5′ AMP-activated protein kinase to mediate the induction of mitochondrial biogenesis and browning via the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator-1 alpha. While this review primarily focuses on mechanistic results from rodent studies special attention is given to the translation of these results, or lack thereof, to human physiology.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatemeh Rajaii ◽  
Dong Won Kim ◽  
Jianbo Pan ◽  
Nicholas R. Mahoney ◽  
Charles G. Eberhart ◽  
...  

AbstractRetrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure. We report that mouse retrobulbar fat is a neural crest-derived tissue histologically and transcriptionally resembles interscapular brown fat. In contrast, human retrobulbar fat closely resembles white adipose tissue. Retrobulbar fat is also brown in other rodents, which are typically housed at temperatures below thermoneutrality, but is white in larger animals. We show that retrobulbar fat in mice housed at thermoneutral temperature show reduced expression of the brown fat marker Ucp1, and histological properties intermediate between white and brown fat. We conclude that retrobulbar fat can potentially serve as a site of active thermogenesis, that this capability is both temperature and species-dependent, and that this may facilitate regulation of intraocular temperature.


Author(s):  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Shohta Kodama

Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. In this review, we review evidence showing the advantages of the spleen as a transplantation site for islets. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets and that splenic stem cells have the potential to differentiate into islet cells. The spleen also has some disadvantages associated with the transplantation procedure itself (bleeding, thrombosis and splenic infarction). The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic to support the engraftment of multiple transplanted islets.


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