Adipocyte Differentiation-Related Protein and OXPAT in Rat and Human Skeletal Muscle: Involvement in Lipid Accumulation and Type 2 Diabetes Mellitus

Minnaard, Ronnie; Schrauwen, Patrick; Schaart, Gert; Jörgensen, Johanna A.; Lenaers, Ellen; Mensink, Marco; Hesselink, Matthijs K. C.

doi:10.1210/jc.2009-0352

Cited by 86 publications

(72 citation statements)

References 37 publications

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“…Studies conflict as to whether the level of PLIN2, or possibly PLIN5, is related to insulin resistance in obese, diabetic individuals (135,136). Tissue-specific ablation of Plin2 and -5 in skeletal muscle will provide important insights into their actions.…”

Section: Lds and Skeletal Muscle Metabolismmentioning

confidence: 99%

The role of lipid droplets in metabolic disease in rodents and humans

Coleman²,

et al. 2011

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Lipid droplets (LDs) are intracellular organelles that store neutral lipids within cells. Over the last two decades there has been a dramatic growth in our understanding of LD biology and, in parallel, our understanding of the role of LDs in health and disease. In its simplest form, the LD regulates the storage and hydrolysis of neutral lipids, including triacylglycerol and/or cholesterol esters. It is becoming increasingly evident that alterations in the regulation of LD physiology and metabolism influence the risk of developing metabolic diseases such as diabetes. In this review we provide an update on the role of LD-associated proteins and LDs in metabolic disease. Overview of lipid dropletsLipid droplets (LDs) are intracellular organelles that store neutral lipids within cells. Over the last two decades there has been a dramatic growth in our understanding of LD biology and, in parallel, our understanding of the role they play in health and disease. LDs regulate the storage and hydrolysis of neutral lipids, including triacylglycerol (TAG) and/or cholesterol esters. For example, adipocytes, the major reservoir of TAG in the body, store their TAG within LDs, and TAG storage in adipocytes is increased in obese animals and humans. The rates of adipocyte lipolysis in many obese individuals are constitutively increased, resulting in elevated levels of circulating fatty acids, which may be stored as TAG in LDs within skeletal muscle and liver. Both local and circulating free fatty acids are thought to be important etiologic agents in the development of insulin resistance, hyperlipidemia, inflammation, and hepatic steatosis (1-3). In this article, we will briefly review the basic characteristics of LDs and then focus on our present knowledge of the current view of the role of LDs in metabolic disease.Cells have developed the capacity to store fatty acids as neutral lipids within LDs for several reasons. An important role of LDs in adipocytes is to store fatty acids as TAG to serve as a reservoir of energetic substrates that can be released when food is scarce. The detrimental effects associated with excess fatty acid entry into cells are often termed "lipotoxicity." Cells protect themselves from these effects by either oxidizing the fatty acids or sequestering them as TAG within LDs. Consistent with this hypothesis, activation of PPARα, which increases the expression of genes that encode oxidative proteins, also increases the expression of LDs and LD-associated proteins (4, 5). PPARγ and PPARδ, along with other transcription factors, can also promote droplet formation (4, 6). As noted above, when fatty acids exceed the oxidative capacity of cells, they not only enhance LD formation, but may also induce apoptosis. An example of the protection LD formation provides was demonstrated in an experiment in which exogenous oleic acid added to fibroblasts deficient in diacylglycerol acyltransferase 1 (DGAT1) promoted lipotoxic cell death. Expression of DGAT1, the terminal step in TAG synthesis, in fibroblasts channeled exces...

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Section: Lds and Skeletal Muscle Metabolismmentioning

confidence: 99%

The role of lipid droplets in metabolic disease in rodents and humans

Coleman²,

et al. 2011

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“…nos. GP34 and GP31; Progen Biotechnik) (7,40,47), ATGL (54 kDa) (rabbit monoclonal antibody no. 2439; Cell Signaling Technology, Danvers, MA) (1), and CGI-58 (42 kDa) rabbit polyclonal antibody (NB110-41576; Novus Biologicals, Oakville, ON, Canada) (1,63).…”

Section: Animalsmentioning

confidence: 99%

Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction

MacPherson

Ramos

Vandenboom

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thought to regulate lipolysis by directly interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. Our purpose was to examine interactions between PLIN2, PLIN3, and PLIN5, with ATGL and its coactivator CGI-58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation [150-ms volleys at 60 Hz with a train rate of 20 tetani/min (25°C)] to maximally stimulate intramuscular lipid breakdown. Results show that the interaction between ATGL and CGI-58 increased 128% following contraction (P ϭ 0.041). Further, ATGL interacts with PLIN2, PLIN3, and PLIN5 at rest and following contraction. The PLIN2-ATGL interaction decreased significantly by 21% following stimulation (P ϭ 0.013). Both PLIN3 and PLIN5 coprecipitated with CGI-58 at rest and following contraction, while there was no detectable interaction between PLIN2 and CGI-58 in either condition. Therefore, our findings indicate that in skeletal muscle, during contraction-induced muscle lipolysis, ATGL and CGI-58 strongly associate and that the PLIN proteins work together to regulate lipolysis, in part, by preventing ATGL and CGI-58 interactions at rest. adipocyte differentiation-related protein; adipophilin; OXPAT; MLDP; TIP47; ABHD5 FATTY ACIDS (FA) RELEASED from intramuscular triglycerides (IMTG) during lipolysis provide an important source of energy during muscle contraction. In skeletal muscle, IMTGs are packaged into lipid droplets that possess a unique coat of proteins associated with the surrounding phospholipid monolayer. This protein coat provides an interface for specific processes, such as transport, lipogenesis, and lipolysis (10, 34). Perilipins (PLINs) are the most recognized family of lipid droplet proteins and are the most likely to be involved in the regulation of lipogenesis and lipolysis in skeletal muscle (31).Our understanding of PLIN proteins in skeletal muscle is limited; however, studies in other tissues and in cell culture indicate that PLIN proteins are key regulators of lipid metabolism, as they appear to be directly involved with how cells and tissues store, mobilize, and utilize fatty acids (8,12,15,34,35,62). The PLIN family consists of five members, PLIN1

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“…In addition to perilipin (PLIN1) and adipose differentiation-related protein (ADRP or PLIN2), three additional members of the PAT family of LD proteins, PLIN3-PLIN5 (also known as TIP47, S3-12 and OXPAT, respectively), are present in vertebrates. They are expressed in variety of organs with different temporal and spatial patterns, reflecting their tissuespecific roles (Dalen et al, 2004;Minnaard et al, 2009;Wang and Sztalryd, 2011). In addition to members of the PAT family, the repertoire of LD proteins in vertebrates also includes the cell-deathinducing DNA fragmentation factor-like effector (CIDE) domain family (CIDEA, CIDEB and CIDEC/FSP27), adding more complexity to LD regulation (Wu et al, 2008).…”

Section: Box 1 Lipid Droplet Proteinsmentioning

confidence: 99%

A comparative perspective on lipid storage in animals

Birsoy

Festuccia

Laplante

2013

Journal of Cell Science

130

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SummaryLipid storage is an evolutionary conserved process that exists in all organisms from simple prokaryotes to humans. In Metazoa, longterm lipid accumulation is restricted to specialized cell types, while a dedicated tissue for lipid storage (adipose tissue) exists only in vertebrates. Excessive lipid accumulation is associated with serious health complications including insulin resistance, type 2 diabetes, cardiovascular diseases and cancer. Thus, significant advances have been made over the last decades to dissect out the molecular and cellular mechanisms involved in adipose tissue formation and maintenance. Our current understanding of adipose tissue development comes from in vitro cell culture and mouse models, as well as recent approaches to study lipid storage in genetically tractable lower organisms. This Commentary gives a comparative insight into lipid storage in uni-and multi-cellular organisms with a particular emphasis on vertebrate adipose tissue. We also highlight the molecular mechanisms and nutritional signals that regulate the formation of mammalian adipose tissue.

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Adipocyte Differentiation-Related Protein and OXPAT in Rat and Human Skeletal Muscle: Involvement in Lipid Accumulation and Type 2 Diabetes Mellitus

Abstract: These results indicate involvement of OXPAT and ADRP in muscular lipid accumulation and type 2 diabetes.

Cited by 86 publications

References 37 publications

The role of lipid droplets in metabolic disease in rodents and humans

The role of lipid droplets in metabolic disease in rodents and humans

Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction

A comparative perspective on lipid storage in animals

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