Insulin induces cristae remodeling by decreasing complex I and increasing UCP1 expression in rat brown adipose tissue

The possibility that recruitment and activation of brown adipose tissue (BAT) thermogenesis could be beneficial for curtailing obesity development in humans prompts a need for a better understanding of the control of these processes [that are often referred to collectively as diet-induced thermogenesis (DIT)]. Dietary conditions are associated with large changes in blood-borne factors that could be responsible for BAT recruitment, but BAT is also innervated by the sympathetic nervous system. To examine the significance of the innervation for DIT recruitment, we surgically denervated the largest BAT depot, i.e., the interscapular BAT depot in mice and exposed the mice at thermoneutrality to a high-fat diet versus a chow diet. Denervation led to an alteration in feeding pattern but did not lead to enhanced obesity, but obesity was achieved with a lower food intake, as denervation increased metabolic efficiency. Conclusively, denervation totally abolished the diet-induced increase in total UCP1 protein levels observed in the intact mice, whereas basal UCP1 expression was not dependent on innervation. The denervation of interscapular BAT did not discernably hyper-recruit other BAT depots, and no UCP1 protein could be detected in the principally browning-competent inguinal white adipose tissue depot under any of the examined conditions. We conclude that intact innervation is essential for diet-induced thermogenesis and that circulating factors cannot by themselves initiate recruitment of brown adipose tissue under obesogenic conditions. Therefore, the processes that link food intake and energy storage to activation of the nervous system are those of significance for the further understanding of diet-induced thermogenesis.

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The Effect of Hyperbaric Therapy on Brown Adipose Tissue in Rats

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18179165 ◽

2021 ◽

Vol 18 (17) ◽

pp. 9165

Author(s):

Chang-Hyung Lee ◽

Young-A Choi ◽

Sung-Jin Heo ◽

Parkyong Song

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Therapeutic Potential ◽

Uncoupling Protein ◽

Peroxisome Proliferator ◽

Sprague Dawley ◽

Protein Levels ◽

Brown Adipose ◽

Ucp1 Expression

Brown adipose tissue (BAT) plays an important role in thermogenic regulation, which contributes to alleviating diet-induced obesity through uncoupling protein 1 (UCP1) expression. While cold exposure and physical exercise are known to increase BAT development and UCP1 expression, the contribution of hyperbaric oxygen (HBO) therapy to BAT maturation remains largely unknown. Here, we show that HBO treatment sufficiently increases BAT volumes and thermogenic protein levels in Sprague-Dawley rats. Through 18F-FDG PET/CT analysis, we found that exposure to high-pressure oxygen (1.5–2.5 ATA) for 7 consecutive days increased radiolabeled glucose uptake and BAT development to an extent comparable to cold exposure. Consistent with BAT maturation, thermogenic protein levels, such as those of UCP1 and peroxisome proliferator-activated receptor γ coactivator 1α (PGC−1α), were largely increased by HBO treatment. Taken together, we suggest HBO therapy as a novel method of inducing BAT development, considering its therapeutic potential for the treatment of metabolic disorders.

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Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat burn injury-induced hypermetabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00098.2012 ◽

2013 ◽

Vol 304 (4) ◽

pp. E331-E341 ◽

Cited By ~ 15

Author(s):

Kikuo Yo ◽

Yong-Ming Yu ◽

Gaofeng Zhao ◽

Ali A. Bonab ◽

Naoki Aikawa ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Burn Injury ◽

Morphological Changes ◽

Resting Metabolic Rate ◽

Injury Model ◽

Brown Adipose ◽

Ucp1 Expression ◽

The Relationship

Hypermetabolism is a prominent feature of burn injury, and altered mitochondria function is presumed to contribute to this state. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity is associated with resting metabolic rate. In this report, we elucidate the relationship between burn injury-induced hypermetabolism and BAT activity and the possible role of the mitochondria-targeted peptide SS31 in attenuating burn injury-induced hypermetabolism by using a rat burn injury model. We demonstrate that burn injury induces morphological changes in interscapular BAT (iBAT). Burn injury was associated with iBAT activation, and this effect was positively correlated with increased energy expenditure. BAT activation was associated with augmentation of mitochondria biogenesis, and UCP1 expression in the isolated iBAT mitochondria. In addition, the mitochondria-targeted peptide SS31 attenuated burn injury-induced hypermetabolism, which was accompanied by suppression of UCP1 expression in isolated mitochondria. Our results suggest that BAT plays an important role in burn injury-induced hypermetabolism through its morphological changes and expression of UCP1.

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Mitochondrial proton leak in obesity-resistant and obesity-prone mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00478.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. R1773-R1780 ◽

Cited By ~ 28

Author(s):

Brian D. Fink ◽

Judy A. Herlein ◽

Katrine Almind ◽

Saverio Cinti ◽

C. Ronald Kahn ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Muscle Tissue ◽

Proton Conductance ◽

High Fat ◽

Interscapular Brown Adipose Tissue ◽

Hindlimb Muscle ◽

Brown Adipose ◽

Ucp1 Expression ◽

Ucp3 Expression

We quantified uncoupling proteins (UCPs) in molar amounts and assessed proton conductance in mitochondria isolated from interscapular brown adipose tissue (IBAT) and hindlimb muscle [known from prior work to contain ectopic brown adipose tissue (BAT) interspersed between muscle fibers] of obesity-resistant 129S6/SvEvTac (129) and obesity-prone C57BL/6 (B6) mice under conditions of low (LF) and high-fat (HF) feeding. With usual feeding, IBAT mitochondrial UCP1 content and proton conductance were greater in 129 mice than B6. However, with HF feeding, UCP1 and proton conductance increased more in B6 mice. Moreover, with HF feeding GDP-inhibitable proton conductance, specific for UCP1, equaled that seen in the 129 strain. UCP1 expression was substantial in mitochondria from hindlimb muscle tissue (ectopic BAT) of 129 mice as opposed to B6 but did not increase with HF feeding in either strain. As expected, muscle UCP3 expression increased with HF feeding in both strains but did not differ by strain. Moreover, the proton conductance of mitochondria isolated from hindlimb muscle tissue did not differ by strain or diet. Our data uncover a response to weight gain in obesity-prone (compared to resistant) mice unrecognized in prior studies that examined only UCP1 mRNA. Obesity-prone mice have the capacity to increase both IBAT UCP1 protein and mitochondrial proton conductance as much or more than obesity-resistant mice. But, this is only achieved only at a higher body mass and, therefore, may be adaptive rather than preventative. Neither obesity-prone nor resistant mice respond to HF feeding by expressing more UCP1 in ectopic BAT within muscle tissue.

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ThermoMouse: An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue

Cell Reports ◽

10.1016/j.celrep.2014.10.066 ◽

2014 ◽

Vol 9 (5) ◽

pp. 1584-1593 ◽

Cited By ~ 54

Author(s):

Andrea Galmozzi ◽

Si B. Sonne ◽

Svetlana Altshuler-Keylin ◽

Yutaka Hasegawa ◽

Kosaku Shinoda ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

In Vivo Model ◽

Brown Adipose ◽

Ucp1 Expression

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Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue

EBioMedicine ◽

10.1016/j.ebiom.2018.10.019 ◽

2018 ◽

Vol 37 ◽

pp. 344-355 ◽

Cited By ~ 5

Author(s):

Yan Qiu ◽

Yingmin Sun ◽

Danqing Xu ◽

Yuanyuan Yang ◽

Xiaojian Liu ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Ucp1 Expression ◽

Approved Drugs ◽

Fda Approved Drugs

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Alternative Polyadenylation and Differential Regulation of Ucp1: Implications for Brown Adipose Tissue Thermogenesis Across Species

Frontiers in Pediatrics ◽

10.3389/fped.2020.612279 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wen-Hsin Lu ◽

Yao-Ming Chang ◽

Yi-Shuian Huang

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Molecular Mechanisms ◽

Uncoupling Protein ◽

Alternative Polyadenylation ◽

Proton Channel ◽

Inner Mitochondrial Membrane ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Ucp1 Expression

Brown adipose tissue (BAT) is a thermogenic organ owing to its unique expression of uncoupling protein 1 (UCP1), which is a proton channel in the inner mitochondrial membrane used to dissipate the proton gradient and uncouple the electron transport chain to generate heat instead of adenosine triphosphate. The discovery of metabolically active BAT in human adults, especially in lean people after cold exposure, has provoked the “thermogenic anti-obesity” idea to battle weight gain. Because BAT can expend energy through UCP1-mediated thermogenesis, the molecular mechanisms regulating UCP1 expression have been extensively investigated at both transcriptional and posttranscriptional levels. Of note, the 3′-untranslated region (3′-UTR) of Ucp1 mRNA is differentially processed between mice and humans that quantitatively affects UCP1 synthesis and thermogenesis. Here, we summarize the regulatory mechanisms underlying UCP1 expression, report the number of poly(A) signals identified or predicted in Ucp1 genes across species, and discuss the potential and caution in targeting UCP1 for enhancing thermogenesis and metabolic fitness.

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