Peroxisome Proliferator-activated Receptor γ Coactivator 1β (PGC-1β), A Novel PGC-1-related Transcription Coactivator Associated with Host Cell Factor

Lin, Jiandie D.; Puigserver, Pere; Donovan, Jerry; Tarr, Paul T.; Spiegelman, Bruce M.

doi:10.1074/jbc.c100631200

Cited by 484 publications

(435 citation statements)

References 22 publications

(29 reference statements)

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“…Both our group and Bruce Spiegelman's group isolated the gene encoding PGC1b, a new homologue of PGC1a. 44,45 Data from our lab have shown that PGC1b is highly expressed in tissues with a high mitochondrial content such as skeletal muscle and the heart, supporting a role in mitochondrial function. However, unlike PGC1a, PGC1b is unaffected in rat liver by food withdrawal or cold exposure, suggesting that PGC1b may play a role in basal mitochondrial function.…”

Section: Targeting Fa Oxidation To Prevent or Treat Lipotoxicitymentioning

confidence: 90%

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

2004

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Obesity and type 2 diabetes mellitus are the major noncommunicable public health problem of the 21st century. The best strategy to tackle this problem is to develop strategies to prevent/treat obesity. However, it is becoming clear that despite successful research identifying weight regulatory pathways, the development of the obesity epidemic is outpacing scientific progress. The lack of success controlling the obesity epidemic in an aging population will result in another subsequent uncontrolled epidemic of complications. Our research focuses on the mechanisms causing lipotoxicity aiming to identify suitable strategies to prevent or at least retard the development of the metabolic syndrome. Previous work using transgenic and knockout mouse models has shown an interplay between white adipose tissue and skeletal muscle linking fatty acid (FA) synthesis with reciprocal effects on FA oxidation. Work from our lab and others suggests that defective adipose tissue is a key link between obesity, insulin resistance and type 2 diabetes mellitus by promoting the development of lipotoxicity in peripheral tissues. We propose a series of models to describe the process by which the adipose tissue could react to an energy-rich environment and responds depending on genetic and physiological factors, impacting on the functions of other peripheral tissues. We suggest that by examining hypotheses that encompass multiple organs and the partitioning of energy between these organs, a suitable strategy can be devised for the treatment of chronic obesity.

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Section: Targeting Fa Oxidation To Prevent or Treat Lipotoxicitymentioning

confidence: 90%

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

2004

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“…Although a faint band was present with a molecular weight over 100 KDa in the PGC-1α KO muscles, taking into account its molecular weight, we do not consider that this band represents PGC-1α. PGC-1β is a very close homolog of PGC-1α and shares extensive sequence identity (Lin et al 2002). In addition to their similarities, PGC-1α and PGC-1β share common protein binding partners and the regulation of certain gene programs in skeletal muscle (Handschin et al 2007).…”

Section: Methodsmentioning

confidence: 99%

Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training

Derbré

Gómez-Cabrera

Nascimento

et al. 2011

AGE

113

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Low mitochondriogenesis is critical to explain loss of muscle function in aging and in the development of frailty. The aim of this work was to explain the mechanism by which mitochondriogenesis is decreased in aging and to determine to which extent it may be prevented by exercise training. We used aged rats and compared them with peroxisome proliferator-activated receptor-γ coactivator-1α deleted mice (PGC-1α KO). PGC-1α KO mice showed a significant decrease in the mitochondriogenic pathway in muscle. In aged rats, we found a loss of exercise-induced expression of PGC-1α, nuclear respiratory factor-1 (NRF-1), and of cytochrome C. Thus muscle mitochondriogenesis, which is activated by exercise training in young animals, is not in aged or PGC-1α KO ones. Other stimuli to increase PGC-1α synthesis apart from exercise training, namely cold induction or thyroid hormone treatment, were effective in young rats but not in aged ones. To sum up, the low mitochondrial biogenesis associated with aging may be due to the lack of response of PGC-1α to different stimuli. Aged rats behave as PGC-1α KO mice. Results reported here highlight the role of PGC-1α in the loss of mitochondriogenesis associated with aging and point to this important transcriptional coactivator as a target for pharmacological interventions to prevent age-associated sarcopenia.

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“…PGC-1a and PGC-1b are preferentially expressed in tissues with high oxidative capacity, such as the heart, slow twitch skeletal muscle and BAT, where they regulate mitochondrial function and cellular metabolism (Puigserver et al, 1998;Wu et al, 1999;Lin et al, 2002;Kamei et al, 2003;St-Pierre et al, 2003). In contrast, PPRC1 exhibits only modest differences in expression across different tissues (Andersson and Scarpulla, 2001).…”

Section: Introductionmentioning

confidence: 99%

Peri‐implantation lethality in mice lacking the PGC‐1‐related coactivator protein

Sun

Feng

et al. 2012

Developmental Dynamics

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Background: Members of the PPARg coactivator-1 (PGC-1) family are central transcriptional coactivators that regulate cell metabolic processes ranging from mitochondrial biogenesis to oxidative respiration. PGC-1-related coactivator (PPRC1 or PRC), initially identified as a member of the PGC-1 family, is believed to regulate mitochondria biogenesis, respiration pathways, and cell proliferation. However, its physiological role is not clearly understood. Here, we investigate the biological functions of PPRC1 in vivo using PPRC1 deficient mice generated by gene targeting. Results: Homozygous deficient PPRC1 mice failed to form egg cylinders and died after implantation but before embryonic day 6.5, whereas mice heterozygous for PPRC1 were viable, fertile and indistinguishable from their wild-type littermates. Furthermore, PPRC1 mRNA was expressed at the embryonic stage before implantation and was rapidly upregulated during the first day of embryoid body formation. The PPRC1 mRNA was then subsequently down-regulated, although its precise function at this stage of development was unclear. Conclusions: This is the first study to suggest a nonredundant role for PPRC1 in mouse early embryonic development. Developmental Dynamics 241:975-983, 2012. V C 2012 Wiley Periodicals, Inc.Key words: embryonic lethality; gene targeting; PGC-1-related coactivator; PGC-1 family Key findings:Disruption of pprc1 gene causes peri-implantation embryonic lethality. Developmental deficiencies in pprc1 2/2 embryos occur during peri-implantation. In vitro culturing of pprc1 2/2 blastocysts is susceptible to growth retardation. PPRC1 mRNA is expressed during preimplantation embryonic development. PPRC1 mRNA is rapidly up-regulated during early embryoid body formation. Accepted 23 February 2012Developmental Dynamics ABBREVIATIONS PGC-1 PPARg coactivator-1 PPRC1 PGC-1-a-related coactivator protein BAT brown adipose tissue ICM inner cell mass TG trophoblast giant cells E3.5 embryonic day 3.5 ESC embryonic stem cell EB embryoid body

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Peroxisome Proliferator-activated Receptor γ Coactivator 1β (PGC-1β), A Novel PGC-1-related Transcription Coactivator Associated with Host Cell Factor

Cited by 484 publications

References 22 publications

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training

Peri‐implantation lethality in mice lacking the PGC‐1‐related coactivator protein

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