Srebp2: A master regulator of sterol and fatty acid synthesis

Madison, Blair B.

doi:10.1194/jlr.c066712

Cited by 186 publications

(164 citation statements)

References 8 publications

(5 reference statements)

Supporting

Mentioning

149

Contrasting

Order By: Relevance

“…In addition to suppression of SREBP-1 target gene expression, we also determined expression levels of SREBP-2 target genes. Srebp-2 has been shown to be the primary physiologic regulator of cholesterol biosynthesis (22). Because we observed significant reduction of hepatic cholesterol in Plin2-null mice, we suspected that SREBP-2 might be altered as well.…”

Section: Plin2-null Mice On Long-term Western Diet Are Protected Frommentioning

confidence: 71%

Perilipin-2 Deletion Impairs Hepatic Lipid Accumulation by Interfering with Sterol Regulatory Element-binding Protein (SREBP) Activation and Altering the Hepatic Lipidome

Libby¹,

Bales²,

Orlicky

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by George CarmanPerilipin-2 (PLIN2) is a constitutively associated cytoplasmic lipid droplet coat protein that has been implicated in fatty liver formation in non-alcoholic fatty liver disease. Mice with or without whole-body deletion of perilipin-2 (Plin2-null) were fed either Western or control diets for 30 weeks. Perilipin-2 deletion prevents obesity and insulin resistance in Western diet-fed mice and dramatically reduces hepatic triglyceride and cholesterol levels in mice fed Western or control diets. Gene and protein expression studies reveal that PLIN2 deletion suppressed SREBP-1 and SREBP-2 target genes involved in de novo lipogenesis and cholesterol biosynthetic pathways in livers of mice on either diet. GC-MS lipidomics demonstrate that this reduction correlated with profound alterations in the hepatic lipidome with significant reductions in both desaturation and elongation of hepatic neutral lipid species. To examine the possibility that lipidomic actions of PLIN2 deletion contribute to suppression of SREBP activation, we isolated endoplasmic reticulum membrane fractions from long-term Western diet-fed wild type (WT) and Plin2-null mice. Lipidomic analyses reveal that endoplasmic reticulum membranes from Plin2-null mice are markedly enriched in -3 and -6 long-chain polyunsaturated fatty acids, which others have shown inhibit SREBP activation and de novo lipogenesis. Our results identify PLIN2 as a determinant of global changes in the hepatic lipidome and suggest the hypothesis that these actions contribute to SREBP-regulated de novo lipogenesis involved in non-alcoholic fatty liver disease.

show abstract

Section: Plin2-null Mice On Long-term Western Diet Are Protected Frommentioning

confidence: 71%

Perilipin-2 Deletion Impairs Hepatic Lipid Accumulation by Interfering with Sterol Regulatory Element-binding Protein (SREBP) Activation and Altering the Hepatic Lipidome

Libby¹,

Bales²,

Orlicky

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The regulation of lipogenic gene expression by insulin and fatty acids is mainly mediated by transcription factors, such as SREBPs. The SREBPs were also found to modulate transcription of genes encoding enzymes of cholesterol and fatty acid synthesis and uptake, including HMGCR, acetyl CoA carboxylase, fatty acid synthase and lipoprotein lipase [82]. Notably, it is SREBP2 which selectively activates de novo cholesterol synthesis by inducing the expression of HMGCR as well as other pertinent enzymes of the cholesterol biosynthesis pathway [83].…”

Section: Discussionmentioning

confidence: 98%

Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

115

View full text Add to dashboard Cite

It is hypothesized that Rhizoma Coptidis (RC) alkaloids exert their hypolipidemic effects primarily by targeting the gastrointestinal tract and liver. Thus, this study was conducted to evaluate the antihyperlipidemic mechanisms of RC alkaloids (at a daily dose of 140mg/kg for 35days) in high-fat and high-cholesterol induced hyperlipidemic B6 mice. After treatment, serum lipid parameters were determined, the expression of lipid metabolism related genes and pathways such as the sterol regulatory element binding proteins (SREBPs) and bile acid signaling in mice were also investigated. Meanwhile, Illumina sequencing was used to investigate the differences in gut microbiota of B6 mice. The results indicated that RC alkaloids reduced the body weight gain and serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total bile acids (TBA) and lipopolysaccharide of B6 mice. Liver fat deposition and epididymal adipose cell size were also deceased in therapy group. RC alkaloids feeding significantly promoted the abundance of Sporobacter termitidis, Alcaligenes faecalis, Akkermansia muciniphila in the gut of mice, whereas, the abundance of Escherichia coli, Desulfovibrio C21_c20, Parabacteroides distasonis was suppressed. The observed antihyperlipidemic effects of RC alkaloids can also be attributed to their action as agonists of FXR and TGR5, activators for SREBP2, LDLR, UCP2 and CYP7A1, inhibitors of HMGCR, TXNIP, TLR4 and JNK. Therefore, this study expands current knowledge on hypolipidemic mechanisms of RC alkaloids and presents new evidence supporting a key role for RC alkaloids as regulators of lipid homeostasis by modulation gut microbiota and hepatic lipid metabolism.

show abstract

“…In rabbit does feed high fat and/or high cholesterol diets, impaired perinatal development partly relates to altered maternal and placental lipid handling. In particular, there is a greater accumulation of lipids in the maternal liver (Montoudis, Boileau, Simoneau, & Lafond, ) and placental labyrinthine zone during pregnancy (Frantz et al, ; Montoudis et al, ; Popják, ; Tarrade et al, ), driven via local changes in the activity of HMG‐CoA‐reductase and/or nSREBP‐2 (Madison, ; Marseille‐Tremblay, Gravel, Lafond, & Mounier, ). Genes involved in cholesterol handling, namely LDL‐R , CD36 , and ABC‐G1 were also downregulated in the placenta in high fat and cholesterol diet‐fed does, with LXR‐α additionally reduced in male but not female fetuses (Tarrade et al, ).…”

Section: Models Of Iugr and Fetal Programmingmentioning

confidence: 99%

Models of Intrauterine growth restriction and fetal programming in rabbits

López-Tello

Álvarez

González-Bulnes³

et al. 2019

Molecular Reproduction Devel

View full text Add to dashboard Cite

Intrauterine growth restriction (IUGR) affects approximately 10% of human pregnancies globally and has immediate and life‐long consequences for offspring health. However, the mechanisms underlying the pathogenesis of IUGR and its association with later health and disease outcomes are poorly understood. To address these knowledge gaps, the use of experimental animals is critically important. Since the 50's different environmental, pharmacological, and surgical manipulations have been performed in the rabbit to improve our knowledge of the control of fetal growth, fetal responses to IUGR, and mechanisms by which offspring may be programmed by an adverse gestational environment. The purpose of this review is therefore to summarize the utility of the rabbit as a model for IUGR research. It first summarizes the knowledge of prenatal and postnatal development in the rabbit and how these events relate to developmental milestones in humans. It then describes the methods used to induce IUGR in rabbits and the knowledge gained about the mechanisms determining prenatal and postnatal outcomes of the offspring. Finally, it discusses the application of state of the art approaches in the rabbit, including high‐resolution ultrasound, magnetic resonance imaging, and gene targeting, to gain a deeper integrative understanding of the physiological and molecular events governing the development of IUGR. Overall, we hope to engage and inspire investigators to employ the rabbit as a model organism when studying pregnancy physiology so that we may advance our understanding of mechanisms underlying IUGR and its consequences in humans and other mammalian species.

show abstract

Srebp2: A master regulator of sterol and fatty acid synthesis

Cited by 186 publications

References 8 publications

Perilipin-2 Deletion Impairs Hepatic Lipid Accumulation by Interfering with Sterol Regulatory Element-binding Protein (SREBP) Activation and Altering the Hepatic Lipidome

Perilipin-2 Deletion Impairs Hepatic Lipid Accumulation by Interfering with Sterol Regulatory Element-binding Protein (SREBP) Activation and Altering the Hepatic Lipidome

Rhizoma Coptidis alkaloids alleviate hyperlipidemia in B6 mice by modulating gut microbiota and bile acid pathways

Models of Intrauterine growth restriction and fetal programming in rabbits

Contact Info

Product

Resources

About