scholarly journals Peroxisome Proliferator-activated Receptor α Activates Transcription of the Brown Fat Uncoupling Protein-1 Gene

2000 ◽  
Vol 276 (2) ◽  
pp. 1486-1493 ◽  
Author(s):  
M. José Barberá ◽  
Agatha Schlüter ◽  
Neus Pedraza ◽  
Roser Iglesias ◽  
Francesc Villarroya ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Brown Fat ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor

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.

scholarly journals Receptor Interacting Protein 140 Regulates Expression of Uncoupling Protein 1 in Adipocytes through Specific Peroxisome Proliferator Activated Receptor Isoforms and Estrogen-Related Receptor α

2007 ◽  
Vol 21 (7) ◽  
pp. 1581-1592 ◽  
Author(s):  
Darja Debevec ◽  
Mark Christian ◽  
Daniel Morganstein ◽  
Asha Seth ◽  
Birger Herzog ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
White Adipocytes ◽  
Receptor Isoforms ◽  
Ucp1 Expression ◽  
Peroxisome Proliferator Activated Receptors ◽  
Estrogen Related Receptor

Abstract Expression of uncoupling protein 1 (Ucp1) mRNA is elevated in differentiated adipocytes derived from brown or white adipose tissue devoid of the nuclear receptor corepressor receptor interacting protein 140 (RIP140). Increased expression is mediated in part by the recruitment of peroxisome proliferator activated receptors α and γ, together with estrogen-related receptor α, which functions through a novel binding site on the Ucp1 enhancer. This demonstrates that regulation of Ucp1 expression in the absence of RIP140 involves derepression of at least three different nuclear receptors. The ability to increase expression of Ucp1 by β-adrenergic signaling is independent of RIP140, as shown by the action of the β3-adrenergic agonist CL 316,243 to stimulate expression in both brown and white adipocytes in the presence and absence of the corepressor. Therefore, the expression of this metabolic uncoupling protein in adipose cells is regulated by inhibition as well as activation of distinct signaling pathways.

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 Endoplasmic Reticulum Stress Impaired Uncoupling Protein 1 Expression via the Suppression of Peroxisome Proliferator-Activated Receptor γ Binding Activity in Mice Beige Adipocytes

2019 ◽  
Vol 20 (2) ◽  
pp. 274 ◽  
Author(s):  
Ana Yuliana ◽  
Asumi Daijo ◽  
Huei-Fen Jheng ◽  
Jungin Kwon ◽  
Wataru Nomura ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beige Adipocytes ◽  
Ucp1 Expression ◽  
Er Homeostasis

Endoplasmic reticulum (ER) homeostasis is critical in maintaining metabolic regulation. Once it is disrupted due to accumulated unfolded proteins, ER homeostasis is restored via activation of the unfolded protein response (UPR); hence, the UPR affects diverse physiological processes. However, how ER stress influences adipocyte functions is not well known. In this study, we investigated the effect of ER stress in thermogenic capacity of mice beige adipocytes. Here, we show that the expression of uncoupling protein 1 (Ucp1) involved in thermoregulation is severely suppressed under ER stress conditions (afflicted by tunicamycin) in inguinal white adipose tissue (IWAT) both in vitro and in vivo. Further investigation showed that extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were both activated after ER stress stimulation and regulated the mRNA levels of Ucp1 and peroxisome proliferator-activated receptor γ (Pparγ), which is known as a Ucp1 transcriptional activator, in vitro and ex vivo. We also found that Pparγ protein was significantly degraded, reducing its recruitment to the Ucp1 enhancer, thereby downregulating Ucp1 expression. Additionally, only JNK inhibition, but not ERK, rescued the Pparγ protein. These findings provide novel insights into the regulatory effect of ER stress on Ucp1 expression via Pparγ suppression in beige adipocytes.

scholarly journals Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPβ

2005 ◽  
Vol 389 (1) ◽  
pp. 47-56 ◽  
Author(s):  
M. Carmen CARMONA ◽  
Elayne HONDARES ◽  
M. Luisa RODRÍGUEZ DE LA CONCEPCIÓN ◽  
Víctor RODRÍGUEZ-SUREDA ◽  
Julia PEINADO-ONSURBE ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Marker Gene ◽  
Gene Promoter ◽  
Brown Fat ◽  
Specific Marker ◽  
Peroxisome Proliferator ◽  
Inhibitory Protein ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor

C/EBPβ (CCAAT/enhancer-binding protein β) is a transcriptional regulator of the UCP1 (uncoupling protein-1) gene, the specific marker gene of brown adipocytes that is responsible for their thermogenic capacity. To investigate the role of C/EBPβ in brown fat, we studied the C/EBPβ-null mice. When placed in the cold, C/EBPβ−/− mice did not maintain body temperature. This cold-sensitive phenotype occurred, although UCP1 and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) gene expression was unaltered in brown fat of C/EBPβ−/− mice. The UCP1 gene promoter was repressed by the truncated inhibitory C/EBPβ isoform LIP (liver-enriched transcriptional inhibitory protein, the truncated inhibitory C/EBPβ isoform). Since C/EBPβ-null mice lack both C/EBPβ isoforms, active LAP (liver-enriched transcriptional activatory protein, the active C/EBPβ isoform) and LIP, the absence of LIP may have a stronger effect than the absence of LAP upon UCP1 gene expression. Gene expression for UCP2 and UCP3 was not impaired in all tissues analysed. In primary brown adipocytes from C/EBPβ−/− mice, induction of gene expression by noradrenaline was preserved. In contrast, the expression of genes related to lipid storage was impaired, as was the amount of triacylglycerol mobilized after acute cold exposure in brown fat from C/EBPβ−/− mice. LPL (lipoprotein lipase) activity was also impaired in brown fat, but not in other tissues of C/EBPβ−/− mice. LPL protein levels were also diminished, but this effect was independent of changes in LPL mRNA, suggesting that C/EBPβ is involved in the post-transcriptional regulation of LPL gene expression in brown fat. In summary, defective thermoregulation owing to the lack of C/EBPβ is associated with the reduced capacity to supply fatty acids as fuels to sustain brown fat thermogenesis.

scholarly journals Pancreatic Islet Adaptation to Fasting Is Dependent on Peroxisome Proliferator-Activated Receptor α Transcriptional Up-Regulation of Fatty Acid Oxidation

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 375-382 ◽  
Author(s):  
Sandrine Gremlich ◽  
Christopher Nolan ◽  
Raphaël Roduit ◽  
Rémy Burcelin ◽  
Marie-Line Peyot ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Pancreatic Islet ◽  
Cellular Response ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Hyperinsulinemic Hypoglycemia ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

The cellular response to fasting and starvation in tissues such as heart, skeletal muscle, and liver requires peroxisome proliferator-activated receptor-α (PPARα)-dependent up-regulation of energy metabolism toward fatty acid oxidation (FAO). PPARα null (PPARαKO) mice develop hyperinsulinemic hypoglycemia in the fasting state, and we previously showed that PPARα expression is increased in islets at low glucose. On this basis, we hypothesized that enhanced PPARα expression and FAO, via depletion of lipid-signaling molecule(s) for insulin exocytosis, are also involved in the normal adaptive response of the islet to fasting. Fasted PPARαKO mice compared with wild-type mice had supranormal ip glucose tolerance due to increased plasma insulin levels. Isolated islets from the PPARα null mice had a 44% reduction in FAO, normal glucose use and oxidation, and enhanced glucose-induced insulin secretion. In normal rats, fasting for 24 h increased islet PPARα, carnitine palmitoyltransferase 1, and uncoupling protein-2 mRNA expression by 60%, 62%, and 82%, respectively. The data are consistent with the view that PPARα, via transcriptionally up-regulating islet FAO, can reduce insulin secretion, and that this mechanism is involved in the normal physiological response of the pancreatic islet to fasting such that hypoglycemia is avoided.

scholarly journals Liraglutide suppresses obesity and promotes browning of white fat via miR-27b in vivo and in vitro

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110550
Author(s):  
Xing Wang ◽  
Shuchun Chen ◽  
Dan Lv ◽  
Zelin Li ◽  
Luping Ren ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
White Adipocytes ◽  
White Fat

Objective To investigate the effect of liraglutide on the browning of white fat and the suppression of obesity via regulating microRNA (miR)-27b in vivo and in vitro. Methods Sprague-Dawley rats were fed a high-fat (HF) diet and 3T3-L1 pre-adipocytes were differentiated into mature white adipocytes. Rats and mature adipocytes were then treated with different doses of liraglutide. The mRNA and protein levels of browning-associated proteins, including uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), CCAAT enhancer binding protein β (CEBPβ), cell death-inducing DFFA-like effector A (CIDEA) and peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), were detected using quantitative real-time polymerase chain reaction and Western blotting. Results Liraglutide decreased body weight and reduced the levels of blood glucose, triglyceride and low-density lipoprotein cholesterol in HF diet-fed rats. Liraglutide increased the levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α in vivo and vitro. The levels of miR-27b were upregulated in HF diet-fed rats, whereas liraglutide reduced the levels of miR-27b. In vitro, overexpression of miR-27b decreased the mRNA and protein levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α. Transfection with the miR-27b mimics attenuated the effect of liraglutide on the browning of white adipocytes. Conclusion Liraglutide induced browning of white adipose through regulation of miR-27b.

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