BSCL2

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Justin J. Rochford - One of the best experts on this subject based on the ideXlab platform.

  • Female adipose tissue-specific BSCL2 knockout mice develop only moderate metabolic dysfunction when housed at thermoneutrality and fed a high-fat diet
    Nature Publishing Group, 2018
    Co-Authors: George D. Mcilroy, Weiping Han, Sharon E. Mitchell, Mirela Delibegović, Justin J. Rochford
    Abstract:

    Abstract Mutations affecting the BSCL2 gene cause the most severe form of congenital generalised lipodystrophy. Affected individuals almost completely lack adipose tissue and suffer from severe diabetes and metabolic complications. Likewise, mice lacking BSCL2 in all tissues have dramatically reduced adipose mass, glucose intolerance and hyperinsulinaemia. However, male adipose tissue-specific BSCL2 knockout mice fail to develop the metabolic dysfunction observed in BSCL2 null mice and BSCL2 deficient patients, despite a similar generalised lack of adipose tissues. Clinical reports indicate gender differences frequently exist in cases of lipodystrophy, with female patients more adversely affected than male patients. We therefore generated and characterised female mice lacking BSCL2 specifically in adipose tissue (Ad-B2(−/−)). We show that female Ad-B2(−/−) mice also develop early-onset lipodystrophy when fed a chow diet and are maintained under standard housing conditions (21 °C) or thermoneutrality (30 °C). Despite this, female Ad-B2(−/−) mice fail to develop severe metabolic dysfunction. Only when female Ad-B2(−/−) mice are maintained at thermoneutrality and fed a high-fat diet do subtle alterations to metabolic homeostasis manifest. This is despite a striking inability to expand adipose mass. Our findings provide further evidence that loss of BSCL2 in non-adipose tissues may contribute to the severity of metabolic dysfunction in this condition

  • BRIEF REPORT The Human Lipodystrophy Gene BSCL2/Seipin May Be Essential for Normal Adipocyte Differentiation
    2013
    Co-Authors: Victoria A Payne, Neil Grimsey, Antoinette Tuthill, Sam Virtue, Sarah L Gray, Edoardo Dalla Nora, Robert K Semple, Justin J. Rochford
    Abstract:

    OBJECTIVE—Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder featuring near complete absence of adipose tissue. Remarkably, although the causative gene, BSCL2, has been known for several years, its molecular function and its role in adipose tissue development have not been elucidated. Therefore, we examined whether BSCL2 is involved in the regulation of adipocyte differentiation and the mechanism whereby pathogenic mutations in BSCL2 cause lipodystrophy. RESEARCH DESIGN AND METHODS—Following the characterization of BSCL2 expression in developing adipocytes, C3H10T1/2 mesenchymal stem cells were generated in which BSCL2 expression was knocked down using short hairpin RNA (shRNA). These cells were used to investigate whether BSCL2 is required for adipogenesis. BSCL2 constructs harboring pathogenic mutations known to cause lipodystrophy were also generate

  • Neuroanatomical characterisation of BSCL2 mRNA in adult mouse brain.
    2013
    Co-Authors: Alastair S. Garfield, Wai S. Chan, Rowena J. Dennis, Daisuke Ito, Lora K. Heisler, Justin J. Rochford
    Abstract:

    Radioactive in situ hybridisation histochemistry analysis of BSCL2 mRNA distribution in coronal section across the rostral-caudal extent of adult mouse brain. Endogenous BSCL2 expression was detected throughout the brain, for full characterisation see Table 1. (A–O) 35S-labelled BSCL2 expression was detected in the piriform cortex (Pir), olfactory tubercle (Tu), islands of Calleja (ICj), caudate putamen (CP) lateral septal nucleus intermediate part (LSI), medial septal nucleus (MS), nucleus of the vertical limb of the diagonal band (VDB), lateral septal nucleus ventral part (LSV), nucleus of the horizontal limb of the diagonal band (HDB), magnocellular preoptic nucleus (MCPO), ventromedial preoptic nucleus (VMPO), median preoptic nucleus (MnPO), medial preoptic nucleus medial part (MPOM), paraventricular thalamic nucleus (PVA), lateral globus pallidus (LGP), supraoptic nucleus (SO), suprachiasmatic nucleus (SCh), subfornical organ (SFO), paraventricular nucleus of the hypothalamus (PVN), zona incerta (ZI), dorsomedial nucleus of the hypothalamus (DMH), ventromedial nucleus of the hypothalamus (VMH), arcuate nucleus of the hypothalamus (ARC), basomedial amygdaloid nucleus (BMA), medial amygdaloid nucleus (MeA), medial habenular (MHb), pyramidal cell layer of the hippocampus (py), granular layer of the dentate gyrus (GrDG), posterior hypothalamus (PH), supramammilliary nucleus medial part (SuMM), premammillary nucleus ventral part (PMV), nucleus of Darkschewitsch (Dk), Edinger-Westphal nucleus (EW), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), periaqueductal grey (PAG), median raphe nucleus (MnR), lateral parabrachial nucleus (LPBN), dorsal tegmental nucleus (DTg), laterodorsal tegmental nucleus (LDTg), locus coeruleus (LC), Barrington’s nucleus (Bar), medial vestibular nucleus (MVe), ambiguous nucleus (Amb), dorsal vagal complex (DVC), hypoglossal nucleus (12N). Scale bar in (A) represents 1 mm and applies to all other images.

  • BSCL2 mRNA distribution within the PVN and DVC.
    2013
    Co-Authors: Alastair S. Garfield, Wai S. Chan, Rowena J. Dennis, Daisuke Ito, Lora K. Heisler, Justin J. Rochford
    Abstract:

    Radioactive in situ hybridisation histochemistry analysis of BSCL2 mRNA distribution in coronal section across three rostral-to-caudal levels of adult PVN and DVC. (A–C) 35S-labelled BSCL2 mRNA expression in the PVN demonstrating robust labelling in the ventral (A), medial magnocellular (B), lateral magnocellular (B, C) and posterior domains (C). Scattered BSCL2 labelled cells were expressed in the anterior and medial (B, C) parvicellular portion. (D–F) 35S-labelled Bslc2 mRNA expression in the DVC was highest within the 10N at the level of the area postrema. Within the NTS the preponderance of BSCL2 mRNA was localised to the medial and ventral domains (E, F). No expression was detected in the area postrema (E). 4v, fourth ventricle; 10N, dorsal motor nucleus of the vagus; 12N, hypoglossal nucleus; AP, area postrema; cc, central canal; PaAP, PVN anterior parvicellular; PaLM, PVN lateral magnocellular; PaMM, PVN medial magnocellular; PaMP, PVN medial parvicellular; PaPo, PVN posterior; PaV, PVN ventral; SolC, NTS commissural; SolDL, NTS dorsolateral; SolG, NTS gelatinous; SolIM, NTS intermediate; SolM, NTS medial; SolV, NTS ventral; SolVL, NTS ventrolateral.

  • Expression of BSCL2 mRNA in adult mouse brain.
    2013
    Co-Authors: Alastair S. Garfield, Wai S. Chan, Rowena J. Dennis, Daisuke Ito, Lora K. Heisler, Justin J. Rochford
    Abstract:

    Autoradiographical visualisation of BSCL2 mRNA in saggital section of the adult mouse brain using radioactive in situ hybridisation histochemistry. (A) Diagrammatic representation of the mouse BSCL2 locus detailing the location of the ISHH riboprobe (not to scale). (B) Endogenous BSCL2 expression as detected by a specific antisense riboprobe revealed strong expression within the basal forebrain (BF), hippocampus (Hippo), hypothalamus (Hypo), dorsal brainstem (dBS) and ventral brainstem (vBS). (C) Corresponding BSCL2 sense riboprobe control.

Lawrence Chan - One of the best experts on this subject based on the ideXlab platform.

  • berardinelli seip congenital lipodystrophy 2 seipin is a cell autonomous regulator of lipolysis essential for adipocyte differentiation
    Molecular and Cellular Biology, 2012
    Co-Authors: Weiqin Chen, Vijay Yechoor, Benny Hungjunn Chang, Michael A Mancini, Pradip K Saha, Sean M Hartig, Lan Li, Vasumathi T Reddy, Yisheng Yang, Lawrence Chan
    Abstract:

    : Mutations in BSCL2 underlie human congenital generalized lipodystrophy. We inactivated BSCL2 in mice to examine the mechanisms whereby absence of BSCL2 leads to adipose tissue loss and metabolic disorders. BSCL2(-/-) mice develop severe lipodystrophy of white adipose tissue (WAT), dyslipidemia, insulin resistance, and hepatic steatosis. In vitro differentiation of both BSCL2(-/-) murine embryonic fibroblasts (MEFs) and stromal vascular cells (SVCs) reveals normal early-phase adipocyte differentiation but a striking failure in terminal differentiation due to unbridled cyclic AMP (cAMP)-dependent protein kinase A (PKA)-activated lipolysis, which leads to loss of lipid droplets and silencing of the expression of adipose tissue-specific transcription factors. Importantly, such defects in differentiation can be largely rescued by inhibitors of lipolysis but not by a gamma peroxisome proliferator-activated receptor (PPARγ) agonist. The residual epididymal WAT (EWAT) in BSCL2(-/-) mice displays enhanced lipolysis. It also assumes a "brown-like" phenotype with marked upregulation of UCP1 and other brown adipose tissue-specific markers. Together with decreased Pref1 but increased C/EBPβ levels, these changes highlight a possible increase in cAMP signaling that impairs terminal adipocyte differentiation in the EWAT of BSCL2(-/-) mice. Our study underscores the fundamental role of regulated cAMP/PKA-mediated lipolysis in adipose differentiation and identifies BSCL2 as a novel cell-autonomous determinant of activated lipolysis essential for terminal adipocyte differentiation.

  • the human lipodystrophy gene product berardinelli seip congenital lipodystrophy 2 seipin plays a key role in adipocyte differentiation
    Endocrinology, 2009
    Co-Authors: Weiqin Chen, Vijay Yechoor, Benny Hungjunn Chang, Keith L March, Lawrence Chan
    Abstract:

    Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In this study, we investigated the role of BSCL2 in the regulation of adipocyte differentiation. BSCL2 mRNA is highly up-regulated during standard hormone-induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the preadipocyte lineage. Knockdown of BSCL2 by short hairpin RNA in C3H10T1/2 cells has no effect on bone morphogenetic protein-4-induced preadipocyte commitment. However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome proliferator-activated receptor-γ agonist pioglitazone at an early stage of differentiation. Interestingly, pioglitazone-induced differentiation in the absence of standard hormone is not associated with up-regulated BSCL2 expression. On the other hand, short hairpin RNA-knockdown of BSCL2 largely blocks pioglitazone-induced adipose differentiation. These experiments suggest that BSCL2 may be essential for normal adipogenesis; it works upstream or at the level of peroxisome proliferator-activated receptor-γ, enabling the latter to exert its full activity during adipogenesis. Loss of BSCL2 function thus interferes with the normal transcriptional cascade of adipogenesis during fat cell differentiation, resulting in near total loss of fat or lipodystrophy.

Hongyuan Yang - One of the best experts on this subject based on the ideXlab platform.

  • gpat3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy
    Human Molecular Genetics, 2020
    Co-Authors: Mingming Gao, George Liu, Lin Liu, Xiaowei Wang, Hoi Yin Mak, Hongyuan Yang
    Abstract:

    Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity of glycerol-3-phosphate acyltransferases (GPATs), and increased GPAT activity may be responsible for the defective adipogenesis under seipin deficiency. Here we generated Seipin-/-Gpat3-/- mice, which had mild but significant recovery of white adipose tissue mass over Seipin-/- mice. The mass of brown adipose tissue (BAT) of the Seipin-/-Gpat3-/- mice was almost completely restored to normal level. Importantly, the Seipin-/-Gpat3-/- mice showed significant improvement in liver steatosis and insulin sensitivity over Seipin-/- mice, which is attributable to the increased BAT mass and to the enhanced browning of the subcutaneous fat of the Seipin-/-Gpat3-/- mice. Together, our results establish a functional link between seipin and GPAT3 in vivo and suggest that GPAT inhibitors may have beneficial effects on BSCL2 patients.

  • seipin ablation in mice results in severe generalized lipodystrophy
    Human Molecular Genetics, 2011
    Co-Authors: Xin Cui, Yuhui Wang, Yin Tang, Yixiao Liu, Liping Zhao, Jingna Deng, Xingui Peng, George Liu, Hongyuan Yang
    Abstract:

    Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is an autosomal recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance and fatty liver. Here, we create the first murine model of BSCL2 by targeted disruption of seipin, the causative gene for BSCL2. Compared with their wild-type littermates, the seipin ―/― mice are viable and of normal weight but display significantly reduced adipose tissue mass, hepatic steatosis, glucose intolerance and hyperinsulinemia. The levels of leptin and adiponectin were both significantly decreased in seipin ―/― mice, so were non-esterified fatty acids upon fasting. Surprisingly, however, hypertriglyceridemia which is common in human BSCL, was not observed in seipin ―/― mice. Our findings suggest a possible tissue-autonomous role of seipin in liver lipid storage. The availability of the seipin ―/― mice should help elucidate the molecular function of seipin and lead to a better understanding of the many metabolic consequences of human BSCL2.

Weiqin Chen - One of the best experts on this subject based on the ideXlab platform.

  • 1-s2.0-S0303720718303460-main-01-2019.pdf
    2019
    Co-Authors: Weiqin Chen
    Abstract:

    BSCL2−/− mice recapitulate many of the major metabolic manifestations in Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) individuals, including lipodystrophy, hepatosteatosis, muscular hypertrophy, and insulin resistance. Metabolic defects in BSCL2−/− mice with regard to glucose and lipid metabolism in skeletal muscle have never been investigated. Here, we identified BSCL2−/− mice displayed reduced intramyocellular triglyceride (IMTG) content but increased glycogen storage predominantly in oxidative type I soleus muscle (SM). These changes were associated with increased incomplete fatty acid oxidation and glycogen synthesis. Interestingly, SM in BSCL2−/− mice demonstrated a fasting duration induced insulin sensitivity which was further confirmed by hyperinsulinemic-euglycemic clamp in SM of overnight fasted BSCL2−/− mice but reversed by raising circulating NEFA levels through intralipid infusion. Furthermore, mice with skeletal muscle-specific inactivation of BSCL2 manifested no changes in muscle deposition of lipids and glycogen, suggesting BSCL2 does not play a cell-autonomous role in muscle lipid and glucose homeostasis. Our study uncovers a novel link between muscle metabolic defects and insulin resistance, and underscores an important role of circulating NEFA in regulating oxidative muscle insulin signaling in BSCL2 lipodystrophy

  • Altered Lipid Metabolism in Residual White Adipose Tissues of BSCL2 Deficient Mice
    2016
    Co-Authors: Weiqin Chen, Hongyi Zhou, Siyang Liu, Cassie J. Fhaner, Bethany C. Gross, Todd A. Lydic, Gavin E. Reid
    Abstract:

    Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that BSCL22/2 mice develop lipodystrophy of white adipose tissue (WAT) due to unbridled lipolysis. The residual epididymal WAT (EWAT) displays a browning phenotype with much smaller lipid droplets (LD) and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and BSCL22/2mice. Analysis of total saponified fatty acids revealed that the residual EWAT of BSCL22/2mice contained a much higher proportion of oleic18:1n9 acid concomitant with a lower proportion of palmitic16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA) remodeling. The acyl chains in major species of triacylglyceride (TG) and diacylglyceride (DG) in the residual EWAT of BSCL22/2 mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, BSCL22/ 2 adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal b-oxidation genes were also markedly increased in BSCL22/2 adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT) was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, BSCL2 is also important in fatty aci

  • Residual BSCL2−/− EWAT and BSCL2+/+ EWAT exhibit differential lipid profiles.
    2013
    Co-Authors: Weiqin Chen, Hongyi Zhou, Siyang Liu, Cassie J. Fhaner, Bethany C. Gross, Todd A. Lydic, Gavin E. Reid
    Abstract:

    A) Inactivation of BSCL2 in mice causes massive loss of epididymal white adipose tissue (EWAT). B) Thin layer chromatography (TLC) analysis of total lipids extracted from EWAT of male non-fasting BSCL2+/+ and BSCL2−/− mice. M: TLC standards. CE: cholesterol ester; TG: triacylglyceride; FFA: free fatty acid, CHO: cholesterol; DG: diacylglyceride; PL: phospholipid. Total lipids from equal amounts of tissue for each genotype were loaded. B) Enzymatic analysis of EWAT triacylglycerides (TG). Results were presented as µg TG per mg tissue. C) Total EWAT TG contents based on total EWAT weights. n = 6-7 each. **: p

  • The residual BSCL2−/− subcutaneous white adipose tissues were not browning but had similar altered lipid metabolism.
    2013
    Co-Authors: Weiqin Chen, Hongyi Zhou, Siyang Liu, Cassie J. Fhaner, Bethany C. Gross, Todd A. Lydic, Gavin E. Reid
    Abstract:

    qPCR analyses of BAT specific genes Ucp1 and Elovl3, lipolytic product activated transcription factor Pparα and its targeted genes Cpt1α and Acox2 (A); and genes involved in elongation, desaturation and TG synthesis (B) in isolated adipocytes from ScWAT of BSCL2+/+ and BSCL2−/− mice. Each sample was pooled from 3-4 6-week-old nonfasting male wild-type and BSCL2−/− mice (n  =  4–5). *: P

  • Lipidomic analysis of DGs by shotgun mass spectrometry of EWAT from BSCL2+/+ and BSCL2−/− mice.
    2013
    Co-Authors: Weiqin Chen, Hongyi Zhou, Siyang Liu, Cassie J. Fhaner, Bethany C. Gross, Todd A. Lydic, Gavin E. Reid
    Abstract:

    DG species were determined using high resolution ESI-MS and confirmed via product ion scan mode CID-MS/MS as described in Methods (n = 3 pooled from 6 animals). Data are expressed as % total DG ion abundance in each genotype. Data are presented as means ± SD. *: p

Wang Yuhui - One of the best experts on this subject based on the ideXlab platform.

  • Adipose-Specific Knockout of Seipin/BSCL2 Results in Progressive Lipodystrophy
    diabetes, 2014
    Co-Authors: Lu Liu, Jiang Qingqing, Wang Xuhong, Zhang Yuxi, Lin, Ruby C. Y., Lam, Sin Man, Shui Guanghou, Zhou Linkang, Li Peng, Wang Yuhui
    Abstract:

    Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy, characterized by an almost complete loss of adipose tissue and severe insulin resistance. BSCL2 is caused by loss-of-function mutations in the BSCL2/SEIPIN gene, which is upregulated during adipogenesis and abundantly expressed in the adipose tissue. The physiological function of SEIPIN in mature adipocytes, however, remains to be elucidated. Here, we generated adipose-specific Seipin knockout (ASKO) mice, which exhibit adipocyte hypertrophy with enlarged lipid droplets, reduced lipolysis, adipose tissue inflammation, progressive loss of white and brown adipose tissue, insulin resistance, and hepatic steatosis. Lipidomic and microarray analyses revealed accumulation/imbalance of lipid species, including ceramides, in ASKO adipose tissue as well as increased endoplasmic reticulum stress. Interestingly, the ASKO mice almost completely phenocopy the fat-specific peroxisome proliferator-activated receptor-gamma (Ppar gamma) knockout (FKO-gamma) mice. Rosiglitazone treatment significantly improved a number of metabolic parameters of the ASKO mice, including insulin sensitivity. Our results therefore demonstrate a critical role of SEIPIN in maintaining lipid homeostasis and function of adipocytes and reveal an intimate relationship between SEIPIN and PPAR-gamma.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000337918200022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Endocrinology & MetabolismSCI(E)PubMed22ARTICLEvangeorgeliu@gmail.com; zdoc66@126.com; h.rob.yang@unsw.edu.au72320-23316

  • Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy
    american journal of physiology endocrinology and metabolism, 2012
    Co-Authors: Cui Xin, Wang Yuhui, Deng Jingna, Xu Guoheng, Peng Xingui, Ju Shenghong, Meng Lingjun, Fei Weihua, Zhang Ling, Liu George
    Abstract:

    Cui X, Wang Y, Meng L, Fei W, Deng J, Xu G, Peng X, Ju S, Zhang L, Liu G, Zhao L, Yang H. Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy. Am J Physiol Endocrinol Metab 302: E705-E713, 2012. First published January 10, 2012; doi:10.1152/ajpendo.00237.2011.-Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance, and fatty liver. BSCL2 is caused by loss-of-function mutations in the BSCL2/seipin gene, which encodes seipin. The essential role for seipin in adipogenesis has recently been established both in vitro and in vivo. However, seipin is highly upregulated at later stages of adipocyte development, and its role in mature adipocytes remains to be elucidated. We therefore generated transgenic mice overexpressing a short isoform of human BSCL2 gene (encoding 398 amino acids) using the adipocyte-specific aP2 promoter. The transgenic mice produced similar to 150% more seipin than littermate controls in white adipose tissue. Surprisingly, the increased expression of seipin markedly reduced the mass of white adipose tissue and the size of adipocytes and lipid droplets. This may be due in part to elevated lipolysis rates in the transgenic mice. Moreover, there was a nearly 50% increase in the triacylglycerol content of transgenic liver. These results suggest that seipin promotes the differentiation of preadipocytes but may inhibit lipid storage in mature adipocytes.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000301791300009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Endocrinology & MetabolismPhysiologySCI(E)21ARTICLE6E705-E71330

  • Seipin ablation in mice results in severe generalized lipodystrophy
    human molecular genetics, 2011
    Co-Authors: Cui Xin, Wang Yuhui, Tang Yin, Liu Yixiao, Zhao Liping, Deng Jingna, Xu Guoheng, Peng Xingui, Ju Shenghong, Liu George
    Abstract:

    Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is an autosomal recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance and fatty liver. Here, we create the first murine model of BSCL2 by targeted disruption of seipin, the causative gene for BSCL2. Compared with their wild-type littermates, the seipin(-/-) mice are viable and of normal weight but display significantly reduced adipose tissue mass, hepatic steatosis, glucose intolerance and hyperinsulinemia. The levels of leptin and adiponectin were both significantly decreased in seipin(-/-) mice, so were non-esterified fatty acids upon fasting. Surprisingly, however, hypertriglyceridemia which is common in human BSCL, was not observed in seipin(-/-) mice. Our findings suggest a possible tissue-autonomous role of seipin in liver lipid storage. The availability of the seipin(-/-) mice should help elucidate the molecular function of seipin and lead to a better understanding of the many metabolic consequences of human BSCL2.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000292560000011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry & Molecular BiologyGenetics & HereditySCI(E)PubMed59ARTICLE153022-30302

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