Genes for Apolipoprotein B and Microsomal Triglyceride Transfer Protein Are Expressed in the Heart

Nielsen, Lars Bo; Véniant, Murielle M.; Borén, Jan; Raabe, Martin; Wong, Jinny S.; Tam, Carmen; Flynn, Laura M.; Vanni-Reyes, Teresa; Gunn, Michael D.; Goldberg, Ira J.; Hamilton, Robert L.; Young, Stephen G.

doi:10.1161/01.cir.98.1.13

Cited by 122 publications

(85 citation statements)

References 12 publications

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“…A recently discovered pathway to reduce excessive cardiac lipids involves the synthesis and secretion of apoBcontaining lipoproteins (172). This mobilization of myocardial TG for lipoprotein secretion is thought to provide the heart with a "safety valve" for the disposal of excess lipids.…”

Section: Cardiac Musclementioning

confidence: 99%

Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores

Zechner

Kienesberger

Haemmerle

et al. 2009

Journal of Lipid Research

475

377

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Fatty acids (FAs) are essential components of all lipid classes and pivotal substrates for energy production in all vertebrates. Additionally, they act directly or indirectly as signaling molecules and, when bonded to amino acid side chains of peptides, anchor proteins in biological membranes. In vertebrates, FAs are predominantly stored in the form of triacylglycerol (TG) within lipid droplets of white adipose tissue. Lipid droplet-associated TGs are also found in most nonadipose tissues, including liver, cardiac muscle, and skeletal muscle. The mobilization of FAs from all fat depots depends on the activity of TG hydrolases. Currently, three enzymes are known to hydrolyze TG, the well-studied hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL), discovered more than 40 years ago, as well as the relatively recently identified adipose triglyceride lipase (ATGL). The phenotype of HSL-and ATGL-deficient mice, as well as the disease pattern of patients with defective ATGL activity (due to mutation in ATGL or in the enzymeʼs activator, CGI-58), suggest that the consecutive action of ATGL, HSL, and MGL is responsible for the complete hydrolysis of a TG molecule. The complex regulation of these enzymes by numerous, partially uncharacterized effectors creates the "lipolysome," a complex metabolic network that contributes to the control of lipid and energy homeostasis. This review focuses on the structure, function, and regulation of lipolytic enzymes with a special emphasis on ATGL.-Zechner, R., P. C. Kienesberger, G. Haemmerle, R. Zimmermann, and A. Lass. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J. Lipid Res. 2009. 50: 3-21.Supplementary key words lipolysis • hydrolase • neutral lipid storage disease Lipid homeostasis reflects a balance of processes, designed to generate fatty acids (FAs) and lipids, deliver them from their site of origin to target tissues, and catabolize them for metabolic purposes. Innumerable genes and signal components are responsible for an integrated communication network between many tissues and organs, including adipose tissue, liver, muscles, the digestive tract, pancreas, and the nervous system. This network ultimately accounts for the accurate regulation of lipid and energy homeostasis. Despite the central physiological importance of these processes for human health, many basic mechanisms regulating the synthesis, uptake, storage, and utilization of lipids remain insufficiently characterized.FAs are vital components of essentially all known organisms. They are important substrates for oxidation and the production of cellular energy. FAs are essential precursors for all lipid classes, including those forming biological membranes. Finally, they are important for protein function in acylated proteins and as ligands for nuclear receptor transcription factors. In contrast to these "beneficial" characteristics, unesterified FAs can become deleterious for cells when present even at relatively low concentrations. The chronic exposure of nona...

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Section: Cardiac Musclementioning

confidence: 99%

Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores

Zechner

Kienesberger

Haemmerle

et al. 2009

Journal of Lipid Research

475

377

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“…Entretanto, a presença de gotículas lipídicas na parede das coronárias e dos capilares de todos os grupos avaliados, demonstra a necessidade de outros estudos para verificar se elas foram acumuladas ao longo do tempo e se conduzirão a processos patológicos, ou se foram oriundas da própria síntese vascular. Nielsen et al 29 sugerem que a secreção de lipoproteínas pelo coração pode representar um caminho de transporte reverso dos triacilgliceróis, pelo qual os miócitos podem descarregar o excesso de molé-culas lipídicas (ácidos graxos livres e triacilgliceróis) não utilizadas como combustível e que poderão exercer efeitos lipotóxicos. Assim, a elevada concentração de lipídeos séricos, juntamente com aqueles presentes no endotélio vascular cardíaco, pode contribuir ou até mesmo agravar a formação das placas ateromatosas.…”

Section: S C U S S ã Ounclassified

Lipídeos séricos e morfologia hepática de ratos alimentados com diferentes fontes lipídicas (óleo de soja, gordura de peixe e porco, margarina e manteiga)

et al. 2011

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OBJETIVO: Analisar as alterações lipídicas séricas e morfológicas hepáticas de ratos alimentados com diferentes fontes lipídicas (óleo de soja, gordura de peixe e porco, margarina e manteiga). MÉTODOS: Os 50 ratos Wistars utilizados no estudo foram divididos em cinco grupos, que durante 28 dias receberam dietas semissintéticas com diferentes fontes lipídicas: óleo de soja, gordura de porco, manteiga, margarina e gordura de peixe. Foram avaliados os pesos corporais, o consumo alimentar e o coeficiente de eficiência alimentar; a atividade da lipase lipoproteica; as concentrações séricas de colesterol total e de lipoproteína de alta densidade - colesterol, triacilgliceróis e albumina, bem como a histologia dos tecidos hepático e cardíaco. RESULTADOS: O tipo de fonte lipídica não influenciou o consumo alimentar, o ganho de peso, o coeficiente de eficiência alimentar dos animais, nem a atividade da lipase lipoproteica, porém promoveu alterações nas concentrações séricas de colesterol total, lipoproteína de alta densidade - colesterol, triacilgliceróis e albumina. Todos os grupos apresentaram gotículas lipídicas nas paredes coronarianas e nos capilares cardíacos, sendo caracterizada como esteatose a deposição de gordura no fígado dos animais que receberam óleo de soja, gordura de peixe, de porco e manteiga. CONCLUSÃO: A fonte lipídica que apresentou os melhores resultados foi o óleo de soja, enquanto o consumo de gordura do peixe causou efeito sérico e tecidual semelhante ao encontrado para as outras fontes lipídicas (gordura de porco, manteiga e margarina), as quais podem contribuir para o surgimento e a progressão das doenças cardiovasculares.

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“…1 is expressed at high levels in the absorptive enterocytes of the intestine and hepatocytes, at moderate levels in the visceral endoderm of the yolk sac during embryonic development, and at relatively low levels in kidney and cardiac muscle (1)(2)(3)(4). In each of these tissues, MTP plays a key role in the assembly and secretion of apoB-containing lipoproteins (1,3,5).…”

Section: Microsomal Triglyceride Transfer Protein (Mtp)mentioning

confidence: 99%

A Deficiency of Microsomal Triglyceride Transfer Protein Reduces Apolipoprotein B Secretion

Leung¹,

Véniant²,

Kim³

et al. 2000

Journal of Biological Chemistry

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Microsomal triglyceride transfer protein (MTP) transfers lipids to apolipoprotein B (apoB) within the endoplasmic reticulum, a process that involves direct interactions between apoB and the large subunit of MTP. Recent studies with heterozygous MTP knockout mice have suggested that half-normal levels of MTP in the liver reduce apoB secretion. We hypothesized that reduced apoB secretion in the setting of half-normal MTP levels might be caused by a reduced MTP:apoB ratio in the endoplasmic reticulum, which would reduce the number of apoB-MTP interactions. If this hypothesis were true, half-normal levels of MTP might have little impact on lipoprotein secretion in the setting of halfnormal levels of apoB synthesis (since the ratio of MTP to apoB would not be abnormally low) and might cause an exaggerated reduction in lipoprotein secretion in the setting of apoB overexpression (since the MTP:apoB ratio would be even lower). To test this hypothesis, we examined the effects of heterozygous MTP deficiency on apoB metabolism in the setting of normal levels of apoB synthesis, half-normal levels of apoB synthesis (heterozygous Apob deficiency), and increased levels of apoB synthesis (transgenic overexpression of human apoB). Contrary to our expectations, half-normal levels of MTP reduced the plasma apoB100 levels to the same extent (ϳ25-35%) at each level of apoB synthesis. In addition, apoB secretion from primary hepatocytes was reduced to a comparable extent at each level of apoB synthesis. Thus, these results indicate that the concentration of MTP within the endoplasmic reticulum rather than the MTP:apoB ratio is the critical determinant of lipoprotein secretion. Finally, we found that heterozygosity for an apoB knockout mutation lowered plasma apoB100 levels more than heterozygosity for an MTP knockout allele. Consistent with that result, hepatic triglyceride accumulation was greater in heterozygous apoB knockout mice than in heterozygous MTP knockout mice. Microsomal triglyceride transfer protein (MTP)1 is expressed at high levels in the absorptive enterocytes of the intestine and hepatocytes, at moderate levels in the visceral endoderm of the yolk sac during embryonic development, and at relatively low levels in kidney and cardiac muscle (1-4). In each of these tissues, MTP plays a key role in the assembly and secretion of apoB-containing lipoproteins (1, 3, 5). MTP is located within the lumen of the endoplasmic reticulum (ER) and is thought to transfer lipids to apoB as that molecule is translated, allowing apoB to assume a proper conformation for forming a spherical lipoprotein with a neutral lipid core (6). In the absence of MTP, triglyceride-rich, apoB-containing lipoproteins cannot be assembled or secreted (3, 6, 7). The mechanism of MTP action has attracted considerable scrutiny. Of note, several lines of evidence have suggested that the assembly of lipoproteins involves a direct interaction between MTP and apoB. First, Wu et al. (8) demonstrated that apoB can be immunoprecipitated from the microsomes of cult...

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Genes for Apolipoprotein B and Microsomal Triglyceride Transfer Protein Are Expressed in the Heart

Abstract: These studies strongly suggest that the heart synthesizes and secretes apoB-containing lipoproteins.

Cited by 122 publications

References 12 publications

Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores

Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores

Lipídeos séricos e morfologia hepática de ratos alimentados com diferentes fontes lipídicas (óleo de soja, gordura de peixe e porco, margarina e manteiga)

A Deficiency of Microsomal Triglyceride Transfer Protein Reduces Apolipoprotein B Secretion

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