Expanding roles for SREBP in metabolism

Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Cell Metabolism (Impact Factor: 16.75). 10/2012; 16(4):414-419. DOI: 10.1016/j.cmet.2012.09.002.

ABSTRACT Sterol regulatory element-binding protein (SREBP) transcription factors regulate cellular lipogenesis and lipid homeostasis. Recent studies reveal expanding roles for SREBPs with the description of new regulatory mechanisms, the identification of unexpected transcriptional targets, and the discovery of functions for SREBPs in type II diabetes, cancer, immunity, neuroprotection, and autophagy.

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Available from: Wei Shao, Aug 30, 2015
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    • "In the Golgi, SREBP is cleaved by site-1 and site-2 proteases to generate active SREBP. Active SREBP is then translocated into the nucleus and promotes transcription of genes involved in lipid metabolism (Shao and Espenshade, 2012). Although SREBP expressed in the gut responds to levels of circulating lipids and cholesterol, the blood-brain-barrier prevents lipids from entering the brain in mammals and de novo lipogenesis is critical for nervous system function (Camargo et al., 2009). "
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    ABSTRACT: Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated in neurodegenerative disease. Here, we find that a key consequence of ROS and neuronal mitochondrial dysfunction is the accumulation of lipid droplets (LD) in glia. In Drosophila, ROS triggers c-Jun-N-terminal Kinase (JNK) and Sterol Regulatory Element Binding Protein (SREBP) activity in neurons leading to LD accumulation in glia prior to or at the onset of neurodegeneration. The accumulated lipids are peroxidated in the presence of ROS. Reducing LD accumulation in glia and lipid peroxidation via targeted lipase overexpression and/or lowering ROS significantly delays the onset of neurodegeneration. Furthermore, a similar pathway leads to glial LD accumulation in Ndufs4 mutant mice with neuronal mitochondrial defects, suggesting that LD accumulation following mitochondrial dysfunction is an evolutionarily conserved phenomenon, and represents an early, transient indicator and promoter of neurodegenerative disease. Copyright © 2015 Elsevier Inc. All rights reserved.
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    • "In mammals, sterol response element binding protein, SREBP, is one of the most important transcription factors in both cholesterol and fatty acid metabolism, with the mammalian SREBP-1c playing a critical role in fatty acid metabolism (Shao & Espenshade, 2012). C. elegans are cholesterol auxotrophs but their SREBP ortholog, sbp-1, plays a critical role in fatty acid metabolism sharing a number of regulatory features and targets with its mammalian counterpart (Kniazeva et al., 2004; McKay et al., 2003). "
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    ABSTRACT: Abstract C. elegans provides a genetically tractable system for deciphering the homeostatic mechanisms that underlie fat regulation in intact organisms. Here, we provide an overview of the recent advances in the C. elegans fat field with particular attention to studies of C. elegans lipid droplets, the complex links between lipases, autophagy, and lifespan, and analyses of key transcriptional regulatory mechanisms that coordinate lipid homeostasis. These studies demonstrate the ancient origins of mammalian and C. elegans fat regulatory pathways and highlight how C. elegans is being used to identify and analyze novel lipid pathways that are then shown to function similarly in mammals. Despite its many advantages, study of fat regulation in C. elegans is currently faced with a number of conceptual and methodological challenges. We critically evaluate some of the assumptions in the field and highlight issues that we believe should be taken into consideration when interpreting lipid content data in C. elegans.
    Critical Reviews in Biochemistry and Molecular Biology 09/2014; 50(1):1-16. DOI:10.3109/10409238.2014.959890 · 5.81 Impact Factor
    • "Peroxisome proliferator activated-receptor-γ (PPARG) is an indispensable transcription factor for adipocyte differentiation inducing specific adipocyte gene expression which results in lipid accumulation and adipocyte maduration (Du et al., 2013). In addition, sterol regulatory element-binding transcription factor 1 (SREBF1) regulates lipid metabolism through the induction of genes which are important for triglyceride uptake, synthesis and storage (Shao and Espenshade, 2012). Nutrition in early life affected muscle expression of PPARG and SREBF1 mRNA in cattle (Du et al., 2010b; Graugnard et al., 2009), which is correlated with different potential of intramuscular adipogenesis. "
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    ABSTRACT: The aim of this study was to evaluate the effect of herbage allowance treatment of native pastures from calf conception to weaning on muscle fiber density and diameter and gene expression (insulin-like growth factor (IGF) system and adipogenesis) during the first year of age of purebred (Hereford and Angus) and crossbred (F1) dams offspring. Forty crossbred calves, offspring of purebred or crossbred dams, were used in a randomized block design with a factorial arrangement of herbage allowance (HA) of native pastures (high and low; 4 vs. 2.5 kg dry matter/kg body weight (BW)) and dam genotype resulting in 4 calf groups (high-purebred, high-crossbred, low-purebred, low-crossbred offspring). Calf BW were registered while blood and Semitendinosus muscle samples were collected at birth, weaning (142 days) and at 380 days old to measure plasma IGF-I concentrations and muscle expression of genes related with the IGF system and adipogenesis by quantitative real time PCR. Calf BW at birth did not differ between calf groups but during the postnatal period, low purebred offspring were lighter (P<0.05) than the other three calf groups. Lean to fat tissue ratio tended to be greater (P=0.08) in high than in low HA offspring. Muscle fiber density did not differ among calf groups, but fiber diameter was greater in low than high and in crossbred than purebred offspring. Plasma IGF-I concentrations were lower (P<0.05) in low purebred offspring than in the other three calf groups. The IGFBP5 mRNA expression was greater in low crossbred offspring when compared to the other three groups and PPARG mRNA expression was greater in high than in low and in purebred than crossbred offspring at birth whereas SREBF1 mRNA expression was greater in high crossbred compared to the other three groups at birth and at weaning. At 380 days, after winter restriction, IGF receptor type 1 (IGF1R) and IGFBP5 mRNA expression were greater in high purebred than in high crossbred offspring. The environment provided by the dams during gestation and lactation is probably influenced by the nutritional plane and genotype of the cow. As a consequence, changes appeared between calf groups in calf BW, body composition, Semitendinosus muscle fiber diameter and expression of genes related with the IGF-I system and adipogenesis.
    Livestock Science 09/2014; 167. DOI:10.1016/j.livsci.2014.07.010 · 1.10 Impact Factor
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