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

Barberà, Maria José; Schlüter, Agatha; Pedraza, Neus; Iglesias, Roser; Villarroya, Francesc; Giralt, Marta

doi:10.1074/jbc.m006246200

Cited by 303 publications

(136 citation statements)

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“…Transcriptional regulation of genes encoding enzymes such as SCD1, ACC1, and FAS is complex, and the direct targets for RIP140 action have yet to be elucidated. In BAT, transcription from the UCP1 gene may be regulated by PPARs, retinoids, and thyroid hormone, as well as through the activation of ␤-adrenergic receptor intracellular signaling pathways (19,(48)(49)(50)(51). Expression of UCP1 has been shown to be induced in WAT in transgenic mice by introduction of an activated form of PPAR␦ (20) and also in human white adipocytes in culture as a result of expression of PGC-1␣ and activation by ligands for PPAR␥ (52).…”

Section: Discussionmentioning

confidence: 99%

“…Many of these metabolic processes are controlled in part by nuclear receptors (4,5), including peroxisome proliferatoractivated receptors (PPARs) (6,7), thyroid hormone receptor (8,9), estrogen receptor ␣ (ER␣) (10,11), and ER-related receptor ␣ (ERR␣) (12). The best characterized of these are the PPARs, with PPAR␥ and PPAR␣ playing an essential role in adipogenesis (13)(14)(15)(16) and in thermogenesis and fatty acid oxidation (17)(18)(19), respectively, whereas recent studies have implicated a role for PPAR␦ in lipid homeostasis (20).…”

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confidence: 99%

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Nuclear receptor corepressor RIP140 regulates fat accumulation

Leonardsson

Steel

Christian

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

340

355

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Nuclear receptors and their coactivators have been shown to function as key regulators of adipose tissue biology. Here we show that a ligand-dependent transcriptional repressor for nuclear receptors plays a crucial role in regulating the balance between energy storage and energy expenditure. Mice devoid of the corepressor protein RIP140 are lean, show resistance to high-fat diet-induced obesity and hepatic steatosis, and have increased oxygen consumption. Although the process of adipogenesis is unaffected, expression of certain lipogenic enzymes is reduced. In contrast, genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1, are markedly increased. Therefore, the maintenance of energy homeostasis requires the action of a transcriptional repressor in white adipose tissue, and ligand-dependent recruitment of RIP140 to nuclear receptors may provide a therapeutic target in the treatment of obesity and related disorders. E nergy homeostasis is a highly regulated process that requires precise control of food intake and energy expenditure (1). The major and most efficient storage of energy occurs in the form of triglycerides in white adipose tissue (WAT), and it is now clear that the adipocyte itself may act as an endocrine cell such that altered adipocyte function would cause changes in systemic energy balance (2, 3). From adipogenic stores, fatty acids are easily mobilized during periods of energy restriction or increased physical activity to provide enough fuel for energy synthesis in the form of ATP. In addition, energy is dissipated by generating heat in brown adipose tissue (BAT) and skeletal muscles by regulating the uncoupling of ATP production from respiration. Many of these metabolic processes are controlled in part by nuclear receptors (4, 5), including peroxisome proliferatoractivated receptors (PPARs) (6, 7), thyroid hormone receptor (8, 9), estrogen receptor ␣ (ER␣) (10, 11), and ER-related receptor ␣ (ERR␣) (12). The best characterized of these are the PPARs, with PPAR␥ and PPAR␣ playing an essential role in adipogenesis (13-16) and in thermogenesis and fatty acid oxidation (17-19), respectively, whereas recent studies have implicated a role for PPAR␦ in lipid homeostasis (20).Nuclear receptors stimulate target gene transcription by recruiting coactivators that are required to remodel chromatin and facilitate the assembly of the basal transcription machinery (21). The key coactivator in metabolic processes is the PPAR␥ coactivator 1␣ (PGC-1␣) (22-25), which was initially shown to promote adaptive thermogenesis in BAT and which has emerged as a target for integrating signals in the regulation of specific metabolic programs in other tissues, including muscle and liver. More recently, the related coactivator PGC-1␤ (26, 27) has been implicated in the regulation of energy expenditure as a potential coactivator for ERR␣ (28). In addition, the p160 family of coactivators has also been found to control energy balance in adipose tissue. For instance, SRC1, in associatio...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nuclear receptor corepressor RIP140 regulates fat accumulation

Leonardsson

Steel

Christian

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

340

355

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“…The plasmid constructs used were 4551 UCP-1-CAT (where the CAT reporter gene is under the control of a 4551-bp full-length 5Ј-flanking region of the UCP-1 promoter) (33), Ϫ3628/Ϫ2283/linked to Ϫ141 CAT corresponding with a deletion mutant of the UCP-1 proximal promoter that does not contain C/EBP binding sites (34) and pCMV ␤-galactosidase (gal) (a viral promoter driving expression of the reporter gene ␤-gal). Ten micrograms of DNA-CAT together with 2 g of DNA-␤-gal (to monitor transfection efficiency) were added to each 10-cm dish.…”

Section: Methodsmentioning

confidence: 99%

Insulin-induced Up-regulated Uncoupling Protein-1 Expression Is Mediated by Insulin Receptor Substrate 1 through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Fetal Brown Adipocytes

Valverde

Arribas

Mur

et al. 2003

Journal of Biological Chemistry

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“…In the Myf5-positive myogenic lineage, the PRDM16 and C/ EBP-β transcriptional complex induces the expression of PPAR-γ and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α), which subsequently induces the differentiation of brown adipocytes [42] . In particular, PGC-1α also cooperates with PPAR-γ and PPAR-α and regulates mitochondrial biogenesis and oxidative metabolism [43,44] . In addition, C/EBP-β has been reported to be a key transcriptional activator of UCP1 expression and the thermogenesis process [32,41] .…”

Section: Differentiation Of Into Brown Adipocytes From Progenitor Cellsmentioning

confidence: 99%

Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells

Park

Kim

Bae

2014

WJSC

219

193

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pattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation (adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: White adipocytes; Brown adipocytes; Beige/ brite adipocytes; Mesenchymal stem cells; Adipogenesis; Thermogenesis; Browning Core tip: Here, we summarize the characteristic differences of the white, brown and beige adipocytes derived from mesenchymal stem cells, including their anatomical location. In particular, we focus on the newly discovered brown-like adipocytes called beige/brite adipocytes. A deeper understanding of the molecular mechanism of these adipocytes may provide clues for overcoming obesity and its associated metabolic diseases. AbstractAdipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue (WAT) or brown adipose tissue (BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold-or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expression

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

Cited by 303 publications

References 55 publications

Nuclear receptor corepressor RIP140 regulates fat accumulation

Nuclear receptor corepressor RIP140 regulates fat accumulation

Insulin-induced Up-regulated Uncoupling Protein-1 Expression Is Mediated by Insulin Receptor Substrate 1 through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Fetal Brown Adipocytes

Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells

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