Seipin, adipogenesis and lipid droplets

Fei, Weihua; Du, Ximing; Yang, Hongyuan

doi:10.1016/j.tem.2011.02.004

Cited by 94 publications

(71 citation statements)

References 44 publications

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“…Higher PA levels in S-KO compared with gS-KO testes may be associated with a diluting effect of normal lipids present in the Leydig cells of gS-KO mice, which express low levels of seipin. Elevated PA levels have also been reported from seipin-deleted yeast and seipin-KO Drosophila (27)(28)(29)(30). We speculate that seipin may participate in the regulation of PA metabolism in testis, thereby controlling LD morphology and formation.…”

Section: Discussionsupporting

confidence: 52%

Lack of testicular seipin causes teratozoospermia syndrome in men

Jiang

Gao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Obesity impairs male fertility, providing evidence for a link between adipose tissue and reproductive function; however, potential consequences of adipose tissue paucity on fertility remain unknown. Lack of s.c. fat is a hallmark of Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), which is caused by mutations in BSCL2-encoding seipin. Mice with a targeted deletion of murine seipin model BSCL2 with severe lipodystrophy, insulin resistance, and fatty liver but also exhibit male sterility. Here, we report teratozoospermia syndrome in a lipodystrophic patient with compound BSCL2 mutations, with sperm defects resembling the defects of infertile seipin null mutant mice. Analysis of conditional mouse mutants revealed that adipocyte-specific loss of seipin causes progressive lipodystrophy without affecting fertility, whereas loss of seipin in germ cells results in complete male infertility and teratozoospermia. Spermatids of the human patient and mice devoid of seipin in germ cells are morphologically abnormal with large ectopic lipid droplets and aggregate in dysfunctional clusters. Elevated levels of phosphatidic acid accompanied with an altered ratio of polyunsaturated to monounsaturated and saturated fatty acids in mutant mouse testes indicate impaired phospholipid homeostasis during spermiogenesis. We conclude that testicular but not adipose tissue-derived seipin is essential for male fertility by modulating testicular phospholipid homeostasis.

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Section: Discussionsupporting

confidence: 52%

Lack of testicular seipin causes teratozoospermia syndrome in men

Jiang

Gao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Previous results and data in this work suggest a fundamental role for SEIPIN/Fld1p in lipid metabolism (3,21). Loss of SEIPIN function can change the quantity and/or distribution of certain lipids, such as PA (21).…”

Section: Seipin and Ppar-gsupporting

confidence: 60%

“…It has been proposed that the absence of SEIPIN may lead to the accumulation of certain phospholipid species, such as phosphatidic acid (PA), which may serve as strong PPAR-g antagonists, thereby causing lipodystrophy (3).…”

mentioning

confidence: 99%

Adipose-Specific Knockout of Seipin/Bscl2 Results in Progressive Lipodystrophy

et al. 2014

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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-γ (Pparγ) knockout (FKO-γ) 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-γ.

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“…Another recent surprising yet exciting fi nding is that both seipin and the yeast seipin homolog, Fld1p, play a critical role in the cellular dynamics of LDs (16)(17)(18). It has been suggested that seipin/Fld1p may regulate the metabolism of fatty acids/phospholipids (phosphatidic acid), and/or the generation of LDs, although the molecular function of seipin remains to be elucidated (19)(20)(21). Seipin is predicted to span the endoplasmic reticulum (ER) membrane twice, with both N-and C termini in the cytoplasm and a large luminal loop ( 10,22 ).…”

Section: Lipid Analysismentioning

confidence: 99%