Borghild Arntsen

University of Oslo, Kristiania (historical), Oslo, Norway

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Publications (7)31.41 Total impact

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    ABSTRACT: The surface of lipid droplets (LDs) in various cell types is coated with perilipin proteins encoded by the Plin genes. Perilipins regulate LD metabolism by selectively recruiting lipases and other proteins to LDs. We have studied the expression of perilipins in mouse muscle. The glycolytic fiber-enriched gastrocnemius muscle expresses predominantly Plin2-4. The oxidative fiber-enriched soleus muscle expresses Plin2-5. Expression of Plin2 and Plin4-5 is elevated in gastrocnemius and soleus muscles from mice fed a high-fat diet. This effect is preserved in peroxisome proliferator-activated receptor-alpha (PPARα) deficient mice. Mouse muscle derived C2C12 cells differentiated into glycolytic fibers increase transcription of these Plins when exposed to various long chain fatty acids (FAs). To understand how FAs regulate Plin genes, we used specific activators and antagonists against PPARs, Plin promoter reporter assays, chromatin immunoprecipitation, siRNA and animal models. Our analyses demonstrate that FAs require PPARδ to induce transcription of Plin4 and Plin5. We further identify a functional PPAR binding site in the Plin5 gene and establish Plin5 as a novel direct PPARδ target in muscle. Our study reveals that muscle cells respond to elevated FAs by increasing transcription of several perilipin LD-coating proteins. This induction renders the muscle better equipped to sequester incoming FAs into cytosolic LDs.
    The Journal of Lipid Research 04/2013; DOI:10.1194/jlr.M038992 · 4.73 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western and non-Western countries, but its pathogenesis is not fully understood. Based on the role of nicotinamide phosphoribosyltransferase (NAMPT) in fat and glucose metabolism and cell survival, we hypothesized a role for NAMPT/visfatin in the pathogenesis of NAFLD-related disease. We conducted clinical studies at a referral medical center in well-characterized NAFLD patients (n = 58) and healthy controls (n = 27). In addition we performed experimental in vitro studies in hepatocytes. We examined 1) the hepatic and systemic expression of NAMPT/visfatin in patients with NAFLD and control subjects, 2) the hepatic regulation of NAMPT/visfatin, and 3) the effect of NAMPT/visfatin on hepatocyte apoptosis. Our main findings were as follows. 1) Patients with NAFLD had decreased NAMPT/visfatin expression both systemically in serum and within the hepatic tissue, with no difference between simple steatosis and nonalcoholic steatohepatitis. 2) By studying the hepatic regulation of NAMPT/visfatin in wild-type and peroxisome proliferators-activated receptor (PPAR)alpha(-/-) mice as well as in hepatocytes, we showed that PPARalpha activation and glucose may be involved in the down-regulation of hepatic NAMPT/visfatin expression in NAFLD. 4) Within the liver, NAMPT/visfatin was located to hepatocytes, and our in vitro studies showed that NAMPT/visfatin exerts antiapoptotic effects in these cells, involving enzymatic synthesis of nicotinamide adenine dinucleotide. Based on these findings, we suggest a role for decreased NAMPT/visfatin levels in hepatocyte apoptosis in NAFLD-related disease.
    The Journal of Clinical Endocrinology and Metabolism 06/2010; 95(6):3039-47. DOI:10.1210/jc.2009-2148 · 6.31 Impact Factor
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    ABSTRACT: The PAT family (originally named for Perilipin, ADFP and TIP47) now includes four members: Perilipins, ADFP, TIP47 and S3-12. Significant primary sequence homology and the ability to associate with lipid storage droplets (LSDs) are well conserved within this family and across species. In this study, we have characterized a novel PAT protein, lipid storage droplet protein 5 (LSDP5) of 463 residues. A detailed sequence analysis of all murine PAT proteins reveals that LSDP5, TIP47 and ADFP share the highest order of sequence similarity, whereas perilipin and S3-12 have more divergent carboxyl- and amino-termini, respectively. Ectopically-expressed YFP-LSDP5 or flag-LSDP5 fusion proteins associate with LSDs. In accord with recent published data for perilipin, forced expression of LSDP5 in CHO cells inhibits lipolysis of intracellular LSDs. The LSDP5 gene is primarily transcribed in cells that actively oxidize fatty acids, such as heart, red muscle and liver. Expression of LSDP5 is stimulated by ligand activation of peroxisomal proliferator-activated receptor alpha (PPARalpha), and significantly reduced in liver and heart in the absence of this transcription factor. PPARalpha is generally required for regulation of fatty acid metabolism during fasting, but fasting induces LSDP5 mRNA in liver even in the absence of PPARalpha.
    Biochimica et Biophysica Acta 03/2007; 1771(2):210-27. DOI:10.1016/j.bbalip.2006.11.011 · 4.66 Impact Factor
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    ABSTRACT: The adipose differentiation-related protein (ADFP)/adipophilin belongs to a family of PAT (for perilipin, ADFP, and TIP47) proteins that associate on the surface of lipid droplets (LDs). Except for LD association, a clear role for ADFP has not been found. We demonstrate that ADFP is transcriptionally regulated by peroxisome proliferator-activated receptor alpha (PPARalpha) in mouse liver and rat and human hepatoma cells through a highly conserved direct repeat-1(DR-1) element. Although the ADFP mRNA is highly increased by a synthetic PPARalpha agonist, the ADFP protein is only substantially increased in cells containing LDs, such as hepatocytes incubated with fatty acids, and in livers of fasted mice. ADFP is induced by fasting even in the absence of a functional PPARalpha, in marked contrast to the PPARalpha target gene acyl-coenzyme A oxidase-1. Activation of LXRs, which stimulates LD formation through the activation of lipogenesis, does not affect ADFP mRNA levels. TIP47, another PAT member known to be expressed in liver, was unaffected by all treatments. This constitutively expressed PAT member seems to be less transcriptionally regulated than ADFP. These observations suggest that ADFP is primarily a fasting-induced protein in liver that coats the newly synthesized triacylglycerol-containing LDs formed during fasting.
    The Journal of Lipid Research 06/2006; 47(5):931-43. DOI:10.1194/jlr.M500459-JLR200 · 4.73 Impact Factor
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    ABSTRACT: This work describes the molecular mechanisms of fatty acid and hormonal modulations of the retinoid X receptor alpha (RXRalpha) in rat liver cells. We examined the effects of different fatty acids (myristic, stearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and several hormones (the glucocorticoid analogue dexamethasone, insulin, and retinoic acid) on the RXRalpha mRNA and protein levels in rat hepatoma cells and cultured hepatocytes. The fatty acids induced the RXRalpha gene expression resulting in up to 3-fold induction. Dexamethasone alone induced the mRNA level and, in combination with fatty acids, an additive or synergistic effect was observed. The dexamethasone-increased mRNA level was obliterated by insulin. The same pattern of regulation of the protein level was observed when determined in cultured hepatocytes, but the induced protein level showed a lower magnitude of stimulation than the mRNA level. This could indicate a post-transcriptional modulation of the RXRalpha gene expression. Time course studies showed a maximal induction of mRNA and protein levels after 18 h and 48 h, respectively. Our results uniformly show that the RXRalpha gene expression is under distinct regulation by fatty acids and hormones which suggests a coupling with the lipid metabolizing system and the hormonal signaling pathway.
    The Journal of Lipid Research 05/1998; 39(4):744-54. · 4.73 Impact Factor
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    ABSTRACT: This work describes the molecular mechanism of fatty acid and hormonal modulation of retinoid X receptor (RXRα) in rat liver. We examined the effects of different fatty acids (myristic-, stearic-, linolenic-, oleic-, arachidonic- and tetradecylthioacetic acid (TTA)) and the synthetic glucocorticoid dexamethasone on RXRα mRNA and protein steady-state levels in hepatoma cells and cultured hepatocytes. Fatty acids induced the RXRα gene expression where TTA showed the most inductive effect (three-fold induction). Dexamethasone alone resulted in a stronger induction (up to seven-fold in hepatocytes), and in combination with fatty acids, an additive or synergistic effect was observed. The RXRα protein level in cultured hepatocytes showed a similar pattern of regulation, with a slight inductive effect of fatty acids and an additive or synergistic effect was observed in combination with dexamethasone. Our results indicate that the RXRα gene expression is under distinct regulation by fatty acids and dexamethasone acid which strongly suggests a coupling with the lipid metabolizing system and the retinoid signaling pathway.
    Biochimie 02/1997; 79(2):107-110. DOI:10.1016/S0300-9084(97)81499-X · 3.12 Impact Factor
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    ABSTRACT: This work describes the molecular mechanism of fatty acid and hormonal modulation of retinoid X receptor (RXR alpha) in rat liver. We examined the effects of different fatty acids (myristic-, stearic-, linolenic-, oleic-, arachidonic- and tetradecylthioacetic acid (TTA)) and the synthetic glucocorticoid dexamethasone on RXR alpha mRNA and protein steady-state levels in hepatoma cells and cultured hepatocytes. Fatty acids induced the RXR alpha gene expression where TTA showed the most inductive effect (three-fold induction). Dexamethasone alone resulted in a stronger induction (up to seven-fold in hepatocytes), and in combination with fatty acids, an additive or synergistic effect was observed. The RXR alpha protein level in cultured hepatocytes showed a similar pattern of regulation, with a slight inductive effect of fatty acids and an additive or synergistic effect was observed in combination with dexamethasone. Our results indicate that the RXR alpha gene expression is under distinct regulation by fatty acids and dexamethasone acid which strongly suggests a coupling with the lipid metabolizing system and the retinoid signaling pathway.
    Biochimie 79(2-3):107-10. · 3.12 Impact Factor