Cardiac lipin 1 expression is regulated by the peroxisome proliferator activated receptor γ coactivator 1α/estrogen related receptor axis.

@article{Mitra2011CardiacL1,
  title={Cardiac lipin 1 expression is regulated by the peroxisome proliferator activated receptor $\gamma$ coactivator 1$\alpha$/estrogen related receptor axis.},
  author={Mayurranjan S. Mitra and Joel D. Schilling and Xiaowei Wang and Patrick Y Jay and Janice M. Huss and Xiong Su and Brian N. Finck},
  journal={Journal of molecular and cellular cardiology},
  year={2011},
  volume={51 1},
  pages={
          120-8
        }
}
Lipin family proteins (lipin 1, 2, and 3) are bifunctional intracellular proteins that regulate metabolism by acting as coregulators of DNA-bound transcription factors and also dephosphorylate phosphatidate to form diacylglycerol [phosphatidate phosphohydrolase activity] in the triglyceride synthesis pathway. Herein, we report that lipin 1 is enriched in heart and that hearts of mice lacking lipin 1 (fld mice) exhibit accumulation of phosphatidate. We also demonstrate that the expression of the… Expand
Complex Interplay between the Lipin 1 and the Hepatocyte Nuclear Factor 4 α (HNF4α) Pathways to Regulate Liver Lipid Metabolism
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The induction of lipin 1 by H NF4α may serve as a mechanism to affect promoter selection to direct HNF4α to promoters of genes encoding fatty acid oxidation enzymes. Expand
Complex interplay between the lipin 1 and the hepatocyte nuclear factor 4 alpha ( HNF 4 alpha ) pathways to regulate liver lipid metabolism
Lipin 1 is a bifunctional protein that serves as a metabolic enzyme in the triglyceride synthesis pathway and regulates gene expression through direct protein-protein interactions with DNA-boundExpand
Differential regulation of the expressions of the PGC-1α splice variants, lipins, and PPARα in heart compared to liver[S]
TLDR
Novel differences in the regulation of lipins, PPARα, and PGC-1α splice variants during fasting in heart versus liver are identified, even though the ultimate outcome in both tissues is to increase FA turnover and oxidation. Expand
Combination of lipid metabolism alterations and their sensitivity to inflammatory cytokines in human lipin-1-deficient myoblasts.
TLDR
The data suggest that the pathogenic mechanism of rhabdomyolysis in lipin-1-deficient patients combines the predisposing constitutive impairment of lipid metabolism and its exacerbation by pro-inflammatory cytokines. Expand
Estrogen-related Receptor γ (ERRγ) Is a Novel Transcriptional Regulator of Phosphatidic Acid Phosphatase, LIPIN1, and Inhibits Hepatic Insulin Signaling*
TLDR
It is reported that nuclear estrogen-related receptor (ERR) γ is a novel transcriptional regulator of LIPIN1 and the selective control of ERRγ transcriptional activity by its specific inverse agonist could provide a novel therapeutic approach to the amelioration of impaired hepatic insulin signaling induced by LipIN1-mediated PKCϵ activation. Expand
Lipin-1 Phosphatidic Phosphatase Activity Modulates Phosphatidate Levels to Promote Peroxisome Proliferator-activated Receptor γ (PPARγ) Gene Expression during Adipogenesis*
TLDR
The results highlight the importance of lipid intermediates as choreographers of gene regulation during adipogenesis, and the results highlight a specific role for lipins as determinants of levels of a phosphatidic acid pool that influences Pparg expression. Expand
PGC-1β and ChREBP partner to cooperatively regulate hepatic lipogenesis in a glucose concentration-dependent manner.
TLDR
The data suggest that PGC-1β-mediated coactivation of ChREBP is involved in the lipogenic response to hyperglycemia. Expand
Peroxisome Proliferator-activated Receptor γ Coactivator 1 (PGC-1)- and Estrogen-related Receptor (ERR)-induced Regulator in Muscle 1 (PERM1) Is a Tissue-specific Regulator of Oxidative Capacity in Skeletal Muscle Cells*
TLDR
These findings support a role for Perm1 acting downstream of PGC-1α and ERRs to regulate muscle-specific pathways important for energy metabolism and contractile function and enable novel approaches for preserving/enhancing muscle function. Expand
Gender Differences in the Expression and Cellular Localization of Lipin 1 in the Hearts of Fructose-Fed Rats
TLDR
The results of this study suggest that fructose diet causes gender-dependent alterations in cardiac lipid metabolism, and potentially detrimental effects of FRD seem to be limited to male rats. Expand
Lipin-1 and lipin-3 together determine adiposity in vivo.
TLDR
It is established thatlipin-1 and lipin-3 cooperate in vivo to determine adipose tissue PAP activity and adiposity, and may have implications in understanding the protection of lipIn-1-deficient humans from overt lipodystrophy. Expand
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Lipin 1 is an inducible amplifier of the hepatic PGC-1α/PPARα regulatory pathway
TLDR
It is demonstrated that the expression of lipin 1 is induced by peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha), a transcriptional coactivators controlling several key hepatic metabolic pathways. Expand
Peroxisome Proliferator-activated Receptor Coactivator-1α (PGC-1α) Coactivates the Cardiac-enriched Nuclear Receptors Estrogen-related Receptor-α and -γ
TLDR
The results identify ERRα and ERRγ as novel PGC-1α interacting proteins, implicate ERR isoforms in the regulation of mitochondrial energy metabolism, and suggest a potential mechanism whereby P GC-1 α selectively binds transcription factor partners. Expand
Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway.
TLDR
It is demonstrated that the expression of lipin 1 is induced by peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha), a transcriptional coactivators controlling several key hepatic metabolic pathways. Expand
Lipin 1 Represses NFATc4 Transcriptional Activity in Adipocytes To Inhibit Secretion of Inflammatory Factors
TLDR
Both lipin 1 protein and total PAP activity are decreased with increasing adiposity in the visceral, but not subcutaneous, fat pads of ob/ob mice, placinglipin 1 as a potentially important link between triacylglycerol synthesis and adipose tissue inflammation. Expand
Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha.
TLDR
These results identify ERRalpha and ERRgamma as novel PGC-1alpha interacting proteins, implicate ERR isoforms in the regulation of mitochondrial energy metabolism, and suggest a potential mechanism whereby P GC-1 alpha selectively binds transcription factor partners. Expand
Lipin 2 Is a Liver-enriched Phosphatidate Phosphohydrolase Enzyme That Is Dynamically Regulated by Fasting and Obesity in Mice*
TLDR
RNAi against lipin 2 markedly reduced PAP-1 activity in hepatocytes from both wild type and fld mice and suppressed triglyceride synthesis under conditions of high fatty acid availability, suggesting thatlipin 2 plays an important role as a hepatic P AP-1 enzyme. Expand
Alterations in Hepatic Metabolism in fld Mice Reveal a Role for Lipin 1 in Regulating VLDL-Triacylglyceride Secretion
TLDR
New and unexpected effects of lipin 1 are revealed on hepatic TAG metabolism and obesity-related hepatic insulin resistance and adenoviral-mediated overexpression oflipin 1 in liver of these mice inhibits VLDL-TAG secretion and improves hepatic diabetes signaling. Expand
A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders.
TLDR
A critical role for PPAR alpha is defined in a transcriptional regulatory response to fasting and the PPARalpha-/- mouse is identified as a potentially useful murine model of inborn and acquired abnormalities of human fatty acid utilization. Expand
An Increase in Murine Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α (PGC-1α) mRNA in Response to Exercise Is Mediated by β-Adrenergic Receptor Activation
A single bout of exercise increases expression of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α mRNA, which may promote mitochondrial biogenesis in skeletal muscle. In brownExpand
Cardiac-Specific Induction of the Transcriptional Coactivator Peroxisome Proliferator-Activated Receptor &ggr; Coactivator-1&agr; Promotes Mitochondrial Biogenesis and Reversible Cardiomyopathy in a Developmental Stage-Dependent Manner
TLDR
Results indicate that PGC-1&agr; drives mitochondrial biogenesis in a developmental stage-dependent manner permissive during the neonatal period, and this unique murine model should prove useful for the study of the molecular regulatory programs governing mitochondrialBiogenesis. Expand
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