The Whitening of Brown Fat and Its Implications for Weight Management in Obesity
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Systemic inflammation resulting from dysfunction of white adipose tissue (WAT) accelerates the pathologies of diabetes and cardiovascular diseases. In contrast to WAT, brown adipose tissue (BAT) is abundant in mitochondria that produce heat by uncoupling respiratory chain process of ATP synthesis. Besides BAT’s role in thermogenesis, accumulating evidence has shown that it is involved in regulating systemic metabolism. Studies have analyzed the “browning” processes of WAT as a means to combat obesity, whereas few studies have focused on the impact and molecular mechanisms that contribute to obesity-linked BAT dysfunction—a process that is associated with the “whitening” of this tissue. Compared to WAT, a dense vascular network is required to support the high energy consumption of BAT. Recently, vascular rarefaction was shown to be a significant causal factor in the whitening of BAT in mouse models. Vascular insufficiency leads to mitochondrial dysfunction and loss in BAT and contributes to systemic insulin resistance. These data suggest that BAT “whitening,” resulting from vascular dysfunction, can impact obesity and obesity-linked diseases. Conversely, agents that promote BAT function could have utility in the treatment of these conditions.
KeywordsObesity Whitening of BAT Insulin resistance VEGF-A
This work was supported by Manpei Suzuki Diabetes Foundation, Kanae Foundation for the Promotion of Medical Science, and Novartis Research Foundation (to IS) and National Institutes of Health (NIH) grants HL081587, HL116591, HL120160, and 126141 (to KW).
Compliance with Ethics Guidelines
Conflict of Interest
Ippei Shimizu and Kenneth Walsh declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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