Recent advance in brown adipose physiology and its therapeutic potential

Lee, Yun Hee; Jung, Young Suk; Choi, Dalwoong

doi:10.1038/emm.2013.163

Cited by 40 publications

(33 citation statements)

References 96 publications

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“…WAT is mainly located in the abdominal and subcutaneous areas of the body and is highly adapted to store excess energy in the form of triacylglycerides. Conversely, beige and brown adipocytes are highly energy-expending (Lee et al., 2014a). They are able to dissipate energy in the form of heat via the action of uncoupling protein-1 (Ucp1) (Tiraby and Langin, 2003).…”

Section: Introductionmentioning

confidence: 99%

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Duteil¹,

Tošić²,

Lausecker³

et al. 2016

Cell Reports

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SummaryPrevious work indicated that lysine-specific demethylase 1 (Lsd1) can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT) and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT)-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT.

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Section: Introductionmentioning

confidence: 99%

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Duteil¹,

Tošić²,

Lausecker³

et al. 2016

Cell Reports

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“…Increasing non-shivering thermogenesis through activating BAT or obtaining BAT-like characteristics in WAT might be an alternative strategy for piglets surviving the cold environment or treating obesity in humans [31,32]. Since the UCP1 defect leads to poor thermogenic ability in piglets, we attempted to restore the ability of uncoupling respiration in the pig preadipocytes and analyze the mechanism of the pig PGC-1α and mice UCP1 work collaboratively to restore uncoupling respiration in pig preadipocytes.…”

Section: Discussionmentioning

confidence: 99%

Browning of Pig White Preadipocytes by Co-Overexpressing Pig PGC-1α and Mice UCP1

Hou

Xie

Cao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Brown adipose tissue (BAT) is critical for mammals’ survival in the cold environment. BAT-dependent non-shivering thermogenesis is attributed to uncoupling protein 1 (UCP1)’s disengagement of oxidative phosphorylation from ATP synthesis and dissipates energy as heat. Thus individuals with a substantial amount of BAT are better equipped during cold stress and less likely to become obese. Recently, our laboratory has shown pig adipocytes have no UCP1 protein. The inability of newborn piglets to generate heat contributed to its high death rate. Repairing the genetic defect of UCP1 in pig adipocytes has implications in defending against cold for piglets and developing an alternative treatment for human obesity. Methods: Q-PCR, western blotting (WB) and oxygen consumption measurement were used to enable functional UCP1 protein in preadipocytes. Immunoprecipitation (IP), chromatin immunoprecipitation (CHIP), and dual-luciferase reporter assay system were used to clarify the thermogenesis mechanism of functional UCP1. Results: Only co-overexpressing mice UCP1 and pig PGC-1α increased not only the mitochondrial number but also the uncoupled respiration rate in the transfected pig adipocytes. The functional mice UCP1 increased the pig PGC-1α activity through the AMPK-SIRT1 pathway. The active form PGC-1α interacted with transcription factors Lhx8, Zic1, ERRα, and PPARα to regulate the expression of mitochondrial energy metabolism and adipocytes browning-related genes. Conclusion: Our data suggest a model in which pig PGC-1α and mice UCP1 work collaboratively to restore uncoupling respiration in pig preadipocytes. These results have great implications for piglet survival and developing an alternative treatment for human obesity in the future.

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“…BAT differs in its primary function from WAT by consuming the formed triacylglycerides for the production of heat (thermogenesis) through the uncoupling of the oxidative respiration from ATP synthesis upon exposure to cold temperatures [26]. Brown adipocytes typically have multiple small lipid droplets and an abundance of iron-containing mitochondria responsible for the brown color of the cells.…”

Section: Types Localization Composition and Function Of Human Adipmentioning

confidence: 99%

When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer

Lapeire

Denys

Cocquyt

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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Since the discovery of leptin in 1994, our vision of adipose tissue as a static organ regulating mainly lipid storage and release has been completely overthrown, and adipose tissue is now seen as an active and integral organ in human physiology. In the past years, extensive research has tremendously given us more insights in the mechanisms and pathways involved not only in normal but also in 'sick' adipose tissue, for example, in obesity and lipodystrophy. With growing evidence of a link between obesity and several types of cancer, research focusing on the interaction between adipose tissue and cancer has begun to unravel the interesting but complex multi-lateral communication between the different players. With breast cancer as one of the first cancer types where a positive correlation between obesity and breast cancer incidence and prognosis in post-menopausal women was found, we have focused this review on the paracrine and endocrine role of adipose tissue in breast cancer initiation and progression. As important inter-species differences in adipose tissue occur, we mainly selected human adipose tissue- and breast cancer-based studies with a short reflection on therapeutic possibilities. This review is part of the special issue on "Adiposopathy in Cancer and (Cardio)Metabolic Diseases".

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Recent advance in brown adipose physiology and its therapeutic potential

Cited by 40 publications

References 96 publications

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Browning of Pig White Preadipocytes by Co-Overexpressing Pig PGC-1α and Mice UCP1

When fat becomes an ally of the enemy: adipose tissue as collaborator in human breast cancer

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