Brown adipose tissue transplantation improves whole-body energy metabolism

Liu, Xiaomeng; Zheng, Zongji; Zhang, Xiaoming; Meng, Minghui; Li, Lan; Shen, Yanyan; Chi, Qing-Sheng; Wang, Dehua; Zhang, Zhaoyun; Li, Chen-Zhong; Li, Yiming; Speakman, John R.; Jin, Wanzhu

doi:10.1038/cr.2013.64

Cited by 198 publications

(188 citation statements)

References 8 publications

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“…Consistent with previous studies (28,33,43), we demonstrate strong ameliorating effects on metabolic disturbance by BAT transplantation. This is the first report to our knowledge that BAT transplantation affects metabolic regulation using an animal model of BAT dysfunction.…”

Section: Discussionsupporting

confidence: 80%

“…In recent decades, it has been reported that the amount of BAT detected using fluorodeoxyglucose-PET and X-ray CT is inversely correlated with BMI and glucose levels in adult humans (6)(7)(8)(9), suggesting a role of BAT in energy expenditure as well as systemic metabolism. Moreover, in recent studies, it has been shown that BAT transplantation has antiobesity effects as well as glucose-lowering effects in diet-induced obesity model mice (28,33), supporting the view that BAT is involved in the regulation of systemic energy and glucose metabolism. Thus, numerous studies, including human research, suggest that BAT is a potentially novel therapeutic target for metabolic diseases such as obesity and diabetes.…”

Section: Discussionmentioning

confidence: 82%

“…Regarding the area of the BAT graft, Stanford et al reported that, compared with these beneficial effects of BAT transplantation into the visceral cavity, transplantation of BAT into the subcutaneous cavity of mice did not result in changes in glucose tolerance (28). However, there have been reports that beneficial metabolic effects were obtained by BAT transplantation into the subcutaneous region (33,43). Further investigation is required to elucidate of the regional regulation of transplanted BAT.…”

Section: Discussionmentioning

confidence: 99%

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Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism

Oguri¹,

Fujita²,

Abulizi³

et al. 2017

JCI Insight

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism

Oguri¹,

Fujita²,

Abulizi³

et al. 2017

JCI Insight

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“…treat obesity and metabolic diseases. Indeed, studies by our group and others have shown that BAT transplantation reverses metabolic disorders in various obese mouse models (17)(18)(19).…”

Section: Significancementioning

confidence: 99%

Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

Yuan

Zhao

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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147

103

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Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS.brown adipose tissue | transplantation | ameliorates | PCOS | adiponectin

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“…The effect of prolonged hyperinsulinemia on functioning of BAT in obese person remains to be explored. The beneficial effects of BAT have motivated scientific community and it is now being stipulated as a promising therapeutic strategy to cure obesity and insulin resistance (Liu et al 2013). Before soliciting further, whether this strategy will work in a hyperinsulinemic obese environment needs to be established.…”

Section: Introductionmentioning

confidence: 99%

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

Rajan

Shankar

Beg

et al. 2016

Journal of Endocrinology

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The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics. CI treatment decreased expression of brown adipocyte-specific markers (such as PRDM16, PGC1α, and UCP1) and mitochondrial content as well as activity. CI-treated brown adipocytes showed drastic decrease in oxygen consumption rate (OCR) and spare respiratory capacity. Morphological study indicates increased accumulation of lipid droplets in CI-treated brown adipocytes. We have further validated these findings in vivo in C57BL/6 mice implanted with mini-osmotic insulin pump for 8 weeks. CI treatment in mice leads to increased body weight gain, fat mass and impaired glucose intolerance with reduced energy expenditure and insulin sensitivity. CI-treated mice showed decreased BAT characteristics and function. We also observed increased inflammation and ER stress markers in BAT of CI-treated animals. The above results conclude that hyperinsulinemia has deleterious effect on brown adipocyte function, making it susceptible to insulin resistance. Thus, the above findings have greater implication in designing approaches for the treatment of insulin resistance and diabetes via recruitment of brown adipocytes.

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Brown adipose tissue transplantation improves whole-body energy metabolism

Cited by 198 publications

References 8 publications

Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism

Tetrahydrobiopterin activates brown adipose tissue and regulates systemic energy metabolism

Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

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