scholarly journals Liver X Receptor α Is a Transcriptional Repressor of the Uncoupling Protein 1 Gene and the Brown Fat Phenotype

2008 ◽  
Vol 28 (7) ◽  
pp. 2187-2200 ◽  
Author(s):  
Haibo Wang ◽  
Yuan Zhang ◽  
Einav Yehuda-Shnaidman ◽  
Alexander V. Medvedev ◽  
Naresh Kumar ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Liver X Receptor ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mechanism Of Inhibition ◽  
Brown Adipose ◽  
Liver X Receptor Α

ABSTRACT The adipocyte integrates crucial information about metabolic needs in order to balance energy intake, storage, and expenditure. Whereas white adipose tissue stores energy, brown adipose tissue is a major site of energy dissipation through adaptive thermogenesis mediated by uncoupling protein 1 (UCP1) in mammals. In both white and brown adipose tissue, nuclear receptors and their coregulators, such as peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator 1α (PGC-1α), play key roles in regulating their development and metabolic functions. Here we show the unexpected role of liver X receptor α (LXRα) as a direct transcriptional inhibitor of β-adrenergic receptor-mediated, cyclic AMP-dependent Ucp1 gene expression through its binding to the critical enhancer region of the Ucp1 promoter. The mechanism of inhibition involves the differential recruitment of the corepressor RIP140 to an LXRα binding site that overlaps with the PPARγ/PGC-1α response element, resulting in the dismissal of PPARγ. The ability of LXRα to dampen energy expenditure in this way provides another mechanism for maintaining a balance between energy storage and utilization.

Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes

2012 ◽  
Vol 302 (2) ◽  
pp. C463-C472 ◽  
Author(s):  
Joo-Young Lee ◽  
Nobuyuki Takahashi ◽  
Midori Yasubuchi ◽  
Young-Il Kim ◽  
Hikari Hashizaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Uncoupling Protein ◽  
Human Adipose Tissue ◽  
Energy Utilization ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Uncoupling protein (UCP)-1 expressed in brown adipose tissue plays an important role in thermogenesis. Recent data suggest that brown-like adipocytes in white adipose tissue (WAT) and skeletal muscle play a crucial role in the regulation of body weight. Understanding of the mechanism underlying the increase in UCP-1 expression level in these organs should, therefore, provide an approach to managing obesity. The thyroid hormone (TH) has profound effects on mitochondrial biogenesis and promotes the mRNA expression of UCP in skeletal muscle and brown adipose tissue. However, the action of TH on the induction of brown-like adipocytes in WAT has not been elucidated. Thus we investigate whether TH could regulate UCP-1 expression in WAT using multipotent cells isolated from human adipose tissue. In this study, triiodothyronine (T3) treatment induced UCP-1 expression and mitochondrial biogenesis, accompanied by the induction of the CCAAT/enhancer binding protein, peroxisome proliferator-activated receptor-γ coactivator-1α, and nuclear respiratory factor-1 in differentiated human multipotent adipose-derived stem cells. The effects of T3 on UCP-1 induction were dependent on TH receptor-β. Moreover, T3 treatment increased oxygen consumption rate. These findings indicate that T3 is an active modulator, which induces energy utilization in white adipocytes through the regulation of UCP-1 expression and mitochondrial biogenesis. Our findings provide evidence that T3 serves as a bipotential mediator of mitochondrial biogenesis.

scholarly journals Adipose-specific C-C motif chemokine ligand (CCL) 19 overexpression drives the mice to both insulin resistance and weight gain

2021 ◽  
Vol 9 (1) ◽  
pp. e001871
Author(s):  
Masato Hayashi ◽  
Misaki Iwashita ◽  
Yuki Nishimura ◽  
Takanori Shinjo ◽  
Tomomi Sano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Normal Diet ◽  
Peroxisome Proliferator ◽  
Suitable Model ◽  
Peroxisome Proliferator Activated Receptor ◽  
Extracellular Signal ◽  
Brown Adipose ◽  
Chemokine Ligand

IntroductionEnlarged adipose tissue is characterized by infiltration of activated immune cells and increased expression of chemokines recruiting these cells including C-C motif ligand 19 (CCL19), although the role of adipose CCL19 is still inconclusive.Research design and methodsAdipocyte-specific Ccl19 knock-in (KI) mice were generated, and the mice were fed either a normal diet or 40% or 60% fat diet (FD) to investigate the effects of CCL19 on the induction of inflammation and lipid metabolism.ResultsCcl19KI mice exhibited increased inflammatory signs in adipose tissue and enlarged subcutaneous white and brown adipose tissue than those of wild-type (WT) mice. The adipose tissue of Ccl19KI mice was characterized by increased extracellular signal-regulated kinase 1/2 and decreased AMP-activated protein kinase α phosphorylation. The protein expression of peroxisome proliferator-activated receptor γ coactivator 1α and uncoupling protein 1 was significantly reduced in brown adipose tissue of Ccl19KI mice compared with that in WT mice. The most remarkable changes between genotypes were observed in mice fed a 40% FD.ConclusionA 40% FD enhanced the effects of CCL19 overexpression, and these mice could be a suitable model to study metabolic disorders in overweight Asians.

scholarly journals Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Kinyui Alice Lo ◽  
Lei Sun
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Uncoupling Protein ◽  
Transcriptional Regulators ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Pr Domain

Adipose tissue has a central role in the regulation of energy balance and homoeostasis. There are two main types of adipose tissue: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT from certain depots, in response to appropriate stimuli, can undergo a process known as browning where it takes on characteristics of BAT, notably the induction of UCP1 (uncoupling protein 1) expression and the presence of multilocular lipid droplets and multiple mitochondria. How browning is regulated is an intense topic of investigation as it has the potential to tilt the energy balance from storage to expenditure, a strategy that holds promise to combat the growing epidemic of obesity and metabolic syndrome. This review focuses on the transcriptional regulators as well as various proteins and secreted mediators that have been shown to play a role in browning. Emphasis is on describing how many of these factors exert their effects by regulating the three main transcriptional regulators of classical BAT development, namely PRDM16 (PR domain containing 16), PPARγ (peroxisome proliferator-activated receptor γ) and PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), which have been shown to be the key nodes in the regulation of inducible brown fat.

scholarly journals Clinical Application Potential of Small Molecules that Induce Brown Adipose Tissue Thermogenesis by Improving Fat Metabolism

2020 ◽  
Vol 29 ◽  
pp. 096368972092739
Author(s):  
Kang-Yun Lu ◽  
Kingsley Theras Primus Dass ◽  
Sheng-Feng Tsai ◽  
Hong-Meng Chuang ◽  
Shinn-Zong Lin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Computed Tomography Images ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Treatment Of Obesity

Mammalian fat comprises white and brown adipose tissue (WAT and BAT, respectively). WAT stores energy, whereas BAT is used for thermogenesis. In recent years, the incidence of obesity and its associated disorders have increased tremendously. Considering the thermogenic capacity and decreased levels of BAT with increasing age, BAT can be used as a suitable therapeutic target for the treatment of obesity and diabetes. In several studies, using positron emission tomography and computed tomography images, adult humans have been shown to have functional BAT in interscapular fat. Results of these basic research studies on BAT have shed light on the new components of transcriptional regulation and the role of hormones in stimulating BAT growth and differentiation. In this review article, we have summarized the thermogenic regulators identified in the past decades by focusing on peroxisome proliferator-activated receptor gamma/uncoupling protein 1 activators, branched-chain amino acids, fatty acids (lipokine), and adenosine monophosphate-activated protein kinase mediators. We have also presented the progress of a few ongoing clinical trials aimed at the treatment of obesity and its associated metabolic disorders. The main purpose of this review was to provide a comprehensive introduction to the latest knowledge of the representative thermogenic regulators for the treatment of obesity. The fat combustion capacity of BAT may have great potential and can be considered as a suitable target for the therapeutic application of drugs from bench-to-bed treatment of obesity and the associated diseases.

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