Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death

Kim, Ji Young; K, Liu; Zhou, Shengli; Tillison, Kristin; Wu, Yuzhang; Smas, Cynthia M.

doi:10.1152/ajpendo.00104.2007

Cited by 58 publications

(69 citation statements)

References 66 publications

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“…1 ). Upregulation of CIDEC by insulin by PI3K was consistent with previous reports in mouse 3T3-L1 adipocytes ( 47 ). These results suggest that the regulatory effects of insulin on both CIDEA and CIDEC expression are mediated via a PI3K-dependent pathway.…”

Section: Both Akt1 and Akt2 Mediate Insulin-induced Downregulation Ofsupporting

confidence: 92%

Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes

Ito¹,

Nagasawa²,

Omae³

et al. 2011

Journal of Lipid Research

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Section: Both Akt1 and Akt2 Mediate Insulin-induced Downregulation Ofsupporting

confidence: 92%

Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes

Ito¹,

Nagasawa²,

Omae³

et al. 2011

Journal of Lipid Research

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“…FSP27 transcript is expressed in both human and murine white adipocytes (13,25) and is present at lower levels in murine brown adipocytes (13). In mice, CIDEA is found only in brown adipocytes (13,44), whereas in humans a high level of CIDEA is noted in white adipocytes (26). CIDEB transcript is markedly enriched in human and murine liver, with expression also reported for murine kidney and intestine (11,13,15).…”

mentioning

confidence: 87%

“…Curiously, the first described function of CIDEs was promotion of apoptosis. FSP27, CIDEA, and CIDEB exert robust apoptotic activity upon ectopic expression in mammalian cells (5,8,11,13,17). CIDE proteins have a region of amino acid sequence homology in their NH 2 -terminal halves, termed the CIDE N domain, that is also present in the major proapoptotic nuclease DFF40 and its inhibitory partner protein DFF45 (11).…”

Section: Ms Smas CMmentioning

confidence: 99%

“…FSP27 and CIDEA are expressed only in adipocytes, with distinctions noted for transcript expression in human vs. mouse. FSP27 transcript is expressed in both human and murine white adipocytes (13,25) and is present at lower levels in murine brown adipocytes (13). In mice, CIDEA is found only in brown adipocytes (13,44), whereas in humans a high level of CIDEA is noted in white adipocytes (26).…”

Section: Ms Smas CMmentioning

confidence: 99%

“…In mice, CIDEA is found only in brown adipocytes (13,44), whereas in humans a high level of CIDEA is noted in white adipocytes (26). CIDEB transcript is markedly enriched in human and murine liver, with expression also reported for murine kidney and intestine (11,13,15).…”

mentioning

confidence: 99%

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Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA

Liu

Zhou

Kim

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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MS, Smas CM.Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA. Am J Physiol Endocrinol Metab 297: E1395-E1413, 2009. First published October 20, 2009 doi:10.1152/ajpendo.00188.2009.-The adipocytespecific protein FSP27, also known as CIDEC, is one of three cell death-inducing DFF45-like effector (CIDE) proteins. The first known function for CIDEs was promotion of apoptosis upon ectopic expression in mammalian cells. Recent studies in endogenous settings demonstrated key roles for CIDEs in energy metabolism. FSP27 is a lipid droplet-associated protein whose heterologous expression enhances formation of enlarged lipid droplets and is required for unilocular lipid droplets typical of white adipocytes in vivo. Here, we delineate relationships between apoptotic function and lipid droplet localization of FSP27. We demonstrate that ectopic expression of FSP27 induces enlarged lipid droplets in multiple human cell lines, which is indicative that its mechanism involves ubiquitously present, rather than adipocyte-specific, cellular machinery. Furthermore, promotion of lipid droplet formation in HeLa cells via culture in exogenous oleic acid offsets FSP27-mediated apoptosis. Using transient cotransfections and analysis of lipid droplets in HeLa cells stably expressing FSP27, we show that FSP27 does not protect lipid droplets from action of ATGL lipase. Domain mapping with eGFP-FSP27 deletion constructs indicates that lipid droplet localization of FSP27 requires amino acids 174 -192 of its CIDE C domain. The apoptotic mechanism of FSP27, which we show involves caspase-9 and mitochondrial cytochrome c, also requires this 19-amino acid region. Interaction assays determine the FSP27 CIDE C domain complexes with CIDEA, and Western blot reveals that FSP27 protein levels are reduced by coexpression of CIDEA. Overall, our findings demonstrate the function of the FSP27 CIDE C domain and/or regions thereof for apoptosis, lipid droplet localization, and CIDEA interaction.fat-specific protein 27; cell death-inducing DFF45-like effector A; adipose OBESITY AND ITS RELATED COMORBIDITIES are approaching epidemic levels (1, 9). The development of new therapeutic inroads to treat these conditions would be greatly facilitated by a full understanding of lipid homeostasis (35,36). Lipotoxicity is a highly detrimental outcome of the obese state, leading to derangement of cell function and/or cell death in various tissues (34,35,37). White adipocytes present in white adipose tissue are the major site storage of excess energy in the form of triacylglycerol, contained within intracellular lipid droplets (7,38). Efficient storage of excess fatty acids within adipocyte lipid droplets also serves to protect other cells and tissues from their lipotoxic effects (7, 38). Lipid droplets are highly dynamic organelles consisting of a neutral lipid core, a phospholipid monolayer, and a large number of lipid droplet-associated proteins (7, 38). The role for the vast majority ...

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CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth

Xu,

Li,

et al. 2024

FEBS Letters

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The cell death‐inducing DFF45‐like effector (CIDE) proteins, including Cidea, Cideb, and Cidec/Fsp27, regulate various aspects of lipid homeostasis, including lipid storage, lipolysis, and lipid secretion. This review focuses on the physiological roles of CIDE proteins based on studies on knockout mouse models and human patients bearing CIDE mutations. The primary cellular function of CIDE proteins is to localize to lipid droplets (LDs) and to control LD fusion and growth across different cell types. We propose a four‐step process of LD fusion, characterized by (a) the recruitment of CIDE proteins to the LD surface and CIDE movement, (b) the enrichment and condensate formation of CIDE proteins to form LD fusion plates at LD–LD contact sites, (c) lipid transfer through lipid‐permeable passageways within the fusion plates, and (d) the completion of LD fusion. Lastly, we outline CIDE‐interacting proteins as regulatory factors, as well as their contribution in LD fusion.

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Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death

Abstract: Smas CM. Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death.

Cited by 58 publications

References 66 publications

Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes

Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes

Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA

CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth

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