The Experts below are selected from a list of 42513 Experts worldwide ranked by ideXlab platform

Pingsheng Liu - One of the best experts on this subject based on the ideXlab platform.

  • the adrenal Lipid Droplet is a new site for steroid hormone metabolism
    Proteomics, 2018
    Co-Authors: Linqiang Zhang, Xiaotong Zhu, Xiaoming Zhou, Haizhen Wang, Hongchao Zhang, Bin Liang, Pingsheng Liu
    Abstract:

    Steroid hormones play essential roles for living organisms. It has been long and well established that the endoplasmic reticulum (ER) and mitochondria are essential sites for steroid hormone biosynthesis because several steroidogenic enzymes are located in these organelles. The adrenal gland Lipid Droplet (LD) proteomes from human, macaque monkey, and rodent are analyzed, revealing that steroidogenic enzymes are also present in abundance on LDs. The enzymes found include 3β-hydroxysteroid dehydrogenase (HSD3B) and estradiol 17β-dehydrogenase 11 (HSD17B11). Analyses by Western blot and subcellular localization consistently demonstrate that HSD3B2 is localized on LDs. Furthermore, in vitro experiments confirm that the isolated LDs from HeLa cell stably expressing HSD3B2 or from rat adrenal glands have the capacity to convert pregnenolone to progesterone. Collectively, these data suggest that LDs may be important sites of steroid hormone metabolism. These findings may bring novel insights into the biosynthesis and metabolism of steroid hormones and the development of treatments for adrenal disorders.

  • dietary fatty acids promote Lipid Droplet diversity through seipin enrichment in an er subdomain
    bioRxiv, 2018
    Co-Authors: Zhe Cao, Guanghou Shui, Pingsheng Liu, Yan Hao, Yiu Yiu Lee, Pengfei Wang, Kang Xie, Wen Jiun Lam, Yifei Qiu, Byungho Kang
    Abstract:

    Exogenous metabolites from microbial and dietary origins have profound effects on host metabolism. Here, we report that a sub-population of Lipid Droplets (LDs), which are conserved organelles for fat storage, is defined by metabolites-driven targeting of the C. elegans seipin ortholog, SEIP-1. Loss of SEIP-1 function reduced the size of a subset of LDs while over-expression of SEIP-1 had the opposite effect. Ultrastructural analysis revealed SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purified with LDs. Analyses of C. elegans and bacterial genetic mutants indicated a requirement of polyunsaturated fatty acids (PUFAs) and microbial cyclopropane fatty acids (CFAs) for SEIP-1 enrichment, as confirmed by dietary supplementation experiments. In mammalian cells, heterologous expression of SEIP-1 promoted Lipid Droplet expansion from ER subdomains in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by enforcing LD diversity.

  • proteome of skeletal muscle Lipid Droplet reveals association with mitochondria and apolipoprotein a i
    Journal of Proteome Research, 2011
    Co-Authors: Huina Zhang, Hongchao Zhang, Yang Wang, Shuyan Zhang, Gong Peng, Fuquan Yang, Pingsheng Liu
    Abstract:

    The Lipid Droplet (LD) is a universal organelle governing the storage and turnover of neutral Lipids. Mounting evidence indicates that elevated intramuscular triglyceride (IMTG) in skeletal muscle LDs is closely associated with insulin resistance and Type 2 Diabetes Mellitus (T2DM). Therefore, the identification of the skeletal muscle LD proteome will provide some clues to dissect the mechanism connecting IMTG with T2DM. In the present work, we identified 324 LD-associated proteins in mouse skeletal muscle LDs through mass spectrometry analysis. Besides Lipid metabolism and membrane traffic proteins, a remarkable number of mitochondrial proteins were observed in the skeletal muscle LD proteome. Furthermore, imaging by fluorescence microscopy and transmission electronic microscopy (TEM) directly demonstrated that mitochondria closely adhere to LDs in vivo. Moreover, our results revealed for the first time that apolipoprotein A-I (apo A-I), the principal apolipoprotein of high density lipoprotein (HDL) part...

Robert V Farese - One of the best experts on this subject based on the ideXlab platform.

  • determinants of endoplasmic reticulum to Lipid Droplet protein targeting
    Developmental Cell, 2020
    Co-Authors: Mariajesus Olarte, Robert V Farese, Siyoung Kim, Morris E Sharp, Jessica M J Swanson, Tobias C Walther
    Abstract:

    Summary Lipid Droplet (LD) formation from the endoplasmic reticulum (ER) is accompanied by the targeting and accumulation of specific hydrophobic, membrane-embedded proteins on LDs. The determinants of this process are unknown. Here, we study the hydrophobic membrane motifs of two Drosophila melanogaster proteins, GPAT4 and ALG14, that utilize this pathway, and we identify crucial sequence features that mediate LD accumulation. Molecular dynamics simulations and studies in cells reveal that LD targeting of these motifs requires deeply inserted tryptophans that have lower free energy in the LD oil phase and positively charged residues near predicted hairpin hinges that become less constrained in the LD environment. Analyzing hydrophobic motifs from similar LD-targeting proteins, it appears that the distribution of tryptophan and positively charged residues distinguishes them from non-LD-targeting membrane motifs. Our studies identify specific sequence features and principles of hydrophobic membrane motifs that mediate their accumulation on LDs.

  • ldaf1 and seipin form a Lipid Droplet assembly complex
    Developmental Cell, 2019
    Co-Authors: Jeeyun Chung, Tobias C Walther, Robert V Farese, Talley J Lambert, Zon Weng Lai
    Abstract:

    Summary Lipid Droplets (LDs) originate from the endoplasmic reticulum (ER) to store triacylglycerol (TG) and cholesterol esters. The ER protein seipin was shown to localize to ER-LD contacts soon after LDs form, but what determines the sites of initial LD biogenesis in the ER is unknown. Here, we identify TMEM159, now re-named Lipid Droplet assembly factor 1 (LDAF1), as an interaction partner of seipin. Together, LDAF1 and seipin form an ∼600 kDa oligomeric complex that copurifies with TG. LDs form at LDAF1-seipin complexes, and re-localization of LDAF1 to the plasma membrane co-recruits seipin and redirects LD formation to these sites. Once LDs form, LDAF1 dissociates from seipin and moves to the LD surface. In the absence of LDAF1, LDs form only at significantly higher cellular TG concentrations. Our data suggest that the LDAF1-seipin complex is the core protein machinery that facilitates LD biogenesis and determines the sites of their formation in the ER.

  • functional genomic screen reveals genes involved in Lipid Droplet formation and utilization
    Nature, 2008
    Co-Authors: Yi Guo, Tobias C Walther, Meghana Rao, Nico Stuurman, Gohta Goshima, Koji Terayama, Jinny S Wong, Ronald D Vale, Peter Walter, Robert V Farese
    Abstract:

    Eukaryotic cells store neutral Lipids in cytoplasmic Lipid Droplets enclosed in a monolayer of phosphoLipids and associated proteins. These dynamic organelles serve as the principal reservoirs for storing cellular energy and for the building blocks for membrane Lipids. Excessive Lipid accumulation in cells is a central feature of obesity, diabetes and atherosclerosis, yet remarkably little is known about Lipid-Droplet cell biology. Here we show, by means of a genome-wide RNA interference (RNAi) screen in Drosophila S2 cells that about 1.5% of all genes function in Lipid-Droplet formation and regulation. The phenotypes of the gene knockdowns sorted into five distinct phenotypic classes. Genes encoding enzymes of phosphoLipid biosynthesis proved to be determinants of Lipid-Droplet size and number, suggesting that the phosphoLipid composition of the monolayer profoundly affects Droplet morphology and Lipid utilization. A subset of the Arf1-COPI vesicular transport proteins also regulated Droplet morphology and Lipid utilization, thereby identifying a previously unrecognized function for this machinery. These phenotypes are conserved in mammalian cells, suggesting that insights from these studies are likely to be central to our understanding of human diseases involving excessive Lipid storage.

Carole Sztalryd - One of the best experts on this subject based on the ideXlab platform.

  • The perilipin family of Lipid Droplet proteins: Gatekeepers of intracellular lipolysis.
    Biochimica et biophysica acta. Molecular and cell biology of lipids, 2017
    Co-Authors: Carole Sztalryd, Dawn L. Brasaemle
    Abstract:

    Lipid Droplets in chordates are decorated by two or more members of the perilipin family of Lipid Droplet surface proteins. The perilipins sequester Lipids by protecting Lipid Droplets from lipase action. Their relative expression and protective nature is adapted to the balance of Lipid storage and utilization in specific cells. Most cells of the body have tiny Lipid Droplets with perilipins 2 and 3 at the surfaces, whereas specialized fat-storing cells with larger Lipid Droplets also express perilipins 1, 4, and/or 5. Perilipins 1, 2, and 5 modulate lipolysis by controlling the access of lipases and co-factors of lipases to substrate Lipids stored within Lipid Droplets. Although perilipin 2 is relatively permissive to lipolysis, perilipins 1 and 5 have distinct control mechanisms that are altered by phosphorylation. Here we evaluate recent progress toward understanding functions of the perilipins with a focus on their role in regulating lipolysis and autophagy. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.

  • the perilipins major cytosolic Lipid Droplet associated proteins and their roles in cellular Lipid storage mobilization and systemic homeostasis
    Annual Review of Nutrition, 2016
    Co-Authors: Alan R Kimmel, Carole Sztalryd
    Abstract:

    The discovery by Dr. Constantine Londos of perilipin 1, the major scaffold protein at the surface of cytosolic Lipid Droplets in adipocytes, marked a fundamental conceptual change in the understanding of lipolytic regulation. Focus then shifted from the enzymatic activation of lipases to substrate accessibility, mediated by perilipin-dependent protein sequestration and recruitment. Consequently, the Lipid Droplet became recognized as a unique, metabolically active cellular organelle and its surface as the active site for novel protein-protein interactions. A new area of investigation emerged, centered on Lipid Droplets' biology and their role in energy homeostasis. The perilipin family is of ancient origin and has expanded to include five mammalian genes and a growing list of evolutionarily conserved members. Universally, the perilipins modulate cellular Lipid storage. This review provides a summary that connects the perilipins to both cellular and whole-body homeostasis.

  • perilipins Lipid Droplet coat proteins adapted for tissue specific energy storage and utilization and Lipid cytoprotection
    Biochimie, 2014
    Co-Authors: Carole Sztalryd, Alan R Kimmel
    Abstract:

    Cytosolic Lipid storage Droplets are primary functional organelles that regulate cellular Lipid metabolism and homeostasis. Paradoxically, excess Lipid stores are linked to both adaptive (fasting and chronic exercise) and mal-adaptive (obesity and related health complications) conditions. Thus, collective metabolic and physiological processes must balance Lipid storage and utilization with prevention of lipocytotoxicity and compounding tissue dysfunctions, urging the need to further define the connection of mammalian Lipid Droplet function and Lipid homeostasis. The perilipins are a multi-protein family that targets Lipid Droplet surfaces and regulates Lipid storage and hydrolysis. Study of perilipin functions has provided insight into the physiological roles of cytosolic Lipid Droplets and their relationship with obesity-related pathologies. Here, we review the current knowledge of the multiple perilipin proteins in regulating tissue-specific Lipid Droplets and associations with tissue and systemic energetics.

Madeleen Bosma - One of the best experts on this subject based on the ideXlab platform.

  • Lipid Droplet dynamics in skeletal muscle
    Experimental Cell Research, 2015
    Co-Authors: Madeleen Bosma
    Abstract:

    The skeletal muscle is subjected to high mechanical and energetic demands. Lipid Droplets are an important source of energy substrates for the working muscle. Muscle cells contain a variety of Lipid Droplets, which are fundamentally smaller than those found in adipocytes. This translates into a greater Lipid Droplet surface area serving as the interface for intracellular Lipid metabolism. The skeletal muscle has a high plasticity, it is subjected to major remodeling following training and detraining. This coincides with adaptations in Lipid Droplet characteristics and dynamics. The majority of Lipid Droplets in skeletal muscle are located in the subsarcolemmal region or in-between the myofibrils, in close vicinity to mitochondria. The vastly organized nature of skeletal muscle fibers limits organelle mobility. The high metabolic rate and substrate turnover in skeletal muscle demands a strict coordination of intramyocellular Lipid metabolism and LD dynamics, in which Lipid Droplet coat proteins play an important role. This review provides insights into the characteristics, diversity and dynamics of skeletal muscle Lipid Droplets.

Ronald P. Kühnlein - One of the best experts on this subject based on the ideXlab platform.

  • The contribution of the Drosophila model to Lipid Droplet research.
    Progress in lipid research, 2011
    Co-Authors: Ronald P. Kühnlein
    Abstract:

    Intracellular Lipid Droplets have long been misconceived as evolutionarily conserved but functionally frugal components of cellular metabolism. An ever-growing repertoire of functions has elevated Lipid Droplets to fully-fledged cellular organelles. Insights into the multifariousness of these organelles have been obtained from a range of model systems now employed for Lipid Droplet research including the fruit fly, Drosophila melanogaster. This review summarizes the progress in fly Lipid Droplet research along four main avenues: the role of Lipid Droplets in fat storage homeostasis, the control of Lipid Droplet structure, the Lipid Droplet surface as a dynamic protein-association platform, and Lipid Droplets as mobile organelles. Moreover, the research potential of the fruit fly model is discussed with respect to the prevailing general questions in Lipid Droplet biology.

  • perilipin dependent control of Lipid Droplet structure and fat storage in drosophila
    Cell Metabolism, 2010
    Co-Authors: Mathias Beller, Anna V Bulankina, Hehsuan Hsiao, Henning Urlaub, Herbert Jackle, Ronald P. Kühnlein
    Abstract:

    Lipid Droplets are intracellular organelles enriched in adipose tissue that govern the body fat stores of animals. In mammals, members of the evolutionarily conserved PERILIPIN protein family are associated with the Lipid Droplet surface and participate in Lipid homeostasis. Here, we show that Drosophila mutants lacking the PERILIPIN PLIN1 are hyperphagic and suffer from adult-onset obesity. PLIN1 is a central and Janus-faced component of fat metabolism. It provides barrier function to storage Lipid breakdown and acts as a key factor of stimulated lipolysis by modulating the access of proteins to the Lipid Droplet surface. It also shapes Lipid Droplet structure, transforming unilocular into multilocular fat cells. We generated flies devoid of all PERILIPIN family members and show that they exhibit impaired yet functional body fat regulation. Our data reveal the existence of a basal and possibly ancient Lipid homeostasis system.

  • characterization of the drosophila Lipid Droplet subproteome
    Molecular & Cellular Proteomics, 2006
    Co-Authors: Mathias Beller, Herbert Jackle, Dietmar Riedel, Lothar Jänsch, Guido Dieterich, Jürgen Wehland, Ronald P. Kühnlein
    Abstract:

    Lipid storage Droplets are universal organelles essential for the cellular and organismal lipometabolism including energy homeostasis. Despite their apparently simple design they are proposed to participate in a growing number of cellular processes, raising the question to what extent the functional multifariousness is reflected by a complex organellar proteome composition. Here we present 248 proteins identified in a subproteome analysis using Lipid storage Droplets of Drosophila melanogaster fat body tissue. In addition to previously known Lipid Droplet-associated PAT (Perilipin, ADRP, and TIP47) domain proteins and homologues of several mammalian Lipid Droplet proteins, this study identified a number of proteins of diverse biological function, including intracellular trafficking supportive of the dynamic and multifaceted character of these organelles. We performed intracellular localization studies on selected newly identified subproteome members both in tissue culture cells and in fat body cells directly. The results suggest that the Lipid Droplets of fat body cells are of combinatorial protein composition. We propose that subsets of Lipid Droplets within single cells are characterized by a protein “zip code,” which reflects functional differences or specific metabolic states. Molecular & Cellular Proteomics 5: 1082–1094, 2006.

  • Characterization of the Drosophila Lipid Droplet Subproteome
    Molecular & cellular proteomics : MCP, 2006
    Co-Authors: Mathias Beller, Herbert Jackle, Dietmar Riedel, Lothar Jänsch, Guido Dieterich, Jürgen Wehland, Ronald P. Kühnlein
    Abstract:

    Lipid storage Droplets are universal organelles essential for the cellular and organismal lipometabolism including energy homeostasis. Despite their apparently simple design they are proposed to participate in a growing number of cellular processes, raising the question to what extent the functional multifariousness is reflected by a complex organellar proteome composition. Here we present 248 proteins identified in a subproteome analysis using Lipid storage Droplets of Drosophila melanogaster fat body tissue. In addition to previously known Lipid Droplet-associated PAT (Perilipin, ADRP, and TIP47) domain proteins and homologues of several mammalian Lipid Droplet proteins, this study identified a number of proteins of diverse biological function, including intracellular trafficking supportive of the dynamic and multifaceted character of these organelles. We performed intracellular localization studies on selected newly identified subproteome members both in tissue culture cells and in fat body cells directly. The results suggest that the Lipid Droplets of fat body cells are of combinatorial protein composition. We propose that subsets of Lipid Droplets within single cells are characterized by a protein "zip code," which reflects functional differences or specific metabolic states.