Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores

Institute of Molecular Biosciences, University of Graz, Austria.
The Journal of Lipid Research (Impact Factor: 4.42). 11/2008; 50(1):3-21. DOI: 10.1194/jlr.R800031-JLR200
Source: PubMed


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 enzyme's 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.

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Available from: Petra Kienesberger, Oct 03, 2015
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    • "More experiments are needed to explore the interaction among these proteins in the process of CLD formation and enlargement in ruminant mammary gland. Adipose triglyceride lipase catalyzes the initial step in the hydrolysis of TG in adipose and other tissues (Zechner et al., 2009). Absence of ATGL in mice increases adipose tissue mass and promotes lipid storage in multiple tissues (Haemmerle et al., 2006). "
    Shi HB · Yu K · Luo J · Li J · Tian HB · Zhu JJ · Sun YT · Yao DW · Xu HF · Shi HP · Loor JJ
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    ABSTRACT: Milk fat originates from the secretion of cytosolic lipid droplets (CLD) synthesized within mammary epithelial cells. Adipocyte differentiation-related protein (ADRP; gene symbol PLIN2) is a CLD-binding protein that is crucial for synthesis of mature CLD. Our hypothesis was that ADRP regulates CLD production and metabolism in goat mammary epithelial cells (GMEC) and thus plays a role in determining milk fat content. To understand the role of ADRP in ruminant milk fat metabolism, ADRP (PLIN2) was overexpressed or knocked down in GMEC using an adenovirus system. Immunocytochemical staining revealed that ADRP localized to the surface of CLD. Supplementation with oleic acid (OA) enhanced its colocalization with CLD surface and enhanced lipid accumulation. Overexpression of ADRP increased lipid accumulation and the concentration of triacylglycerol in GMEC. In contrast, morphological examination revealed that knockdown of ADRP decreased lipid accumulation even when OA was supplemented. This response was confirmed by the reduction in mass of cellular TG when ADRP was knocked down. The fact that knockdown of ADRP did not completely eliminate lipid accumulation at a morphological level in GMEC without OA suggests that some other compensatory factors may also aid in the process of CLD formation. The ADRP reversed the decrease of CLD accumulation induced by adipose triglyceride lipase. This is highly suggestive of ADRP promoting triacylglycerol stability within CLD by preventing access to adipose triglyceride lipase. Collectively, these data provide direct in vitro evidence that ADRP plays a key role in CLD formation and stability in GMEC. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
    Journal of Dairy Science 08/2015; DOI:10.3168/jds.2015-9452 · 2.57 Impact Factor
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    • "FABP3 gene has been shown to be associated with IMF content (Lee et al. 2010). Hormone-sensitive lipase gene (LIPE), which maps to chromosome 6 (Mellink et al. 1993), has been involved in the free fatty acids mobilization (Miyoshi et al. 2008; Zechner et al. 2009). Lipoprotein lipase gene (LPL) maps to chromosome 14 (Gu et al. 1992) and is responsible for lipid deposition and mobilization (Luo et al. 2009). "
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    ABSTRACT: The aim of the present study was to investigate the associations of single nucleotide polymorphisms (SNPs) in candidate genes with fatness traits in the Longissimus dorsi muscle of pigs. The polymorphisms of genes were investigated, which included beta-3-adrenergic receptor gene (ADRB3), heart fatty acid-binding protein gene (FABP3), and hormone-sensitive lipase gene (LIPE) as well as lipoprotein lipase gene (LPL). The intramuscular fat (IMF) content and fatty acid composition contents in Longissimus dorsi muscle samples were measured. Results showed that ADRB3, LIPE, and LPL SNPs were associated with IMF content (P < 0.05). ADRB3 AG heterozygotes exhibited higher IMF content. LIPE A allele was associated with greater IMF content. LPL CT heterozygotes exhibited the lowest IMF content. ADRB3 c.1192G>A had highly significant association with the total monounsaturated fatty acid (MUFA) (P < 0.01) and the total polyunsaturated fatty acid (PUFA) (P < 0.01). LIPE c.442G>A was significantly associated with the contents of C12:0 and C14:0 (P < 0.05). LPL c.624C>T was significantly associated with the percentage of C16:1 (P < 0.05) and the percentage of total saturated fatty acid (SFA) (P < 0.05). The pigs with ADRB3 G allele had more MUFA, and the pigs with LPL T allele had less SFA, implying that the ADRB3 G and LPL T in pigs may be beneficial to human health. In conclusion, the results suggest that these genetic markers are important sources of the variations for the pork selection to obtain favourable meat with higher IMF levels and appropriate fatty acid composition.
    Czech Journal of Animal Science 02/2015; 60(2):60-66. DOI:10.17221/7975-CJAS · 1.18 Impact Factor
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    • "Norepinephrine and epinephrine may induce insulin resistance via multiple mechanisms including up-regulation of glycogenolysis and gluconeogenesis (Barth et al., 2007; Ziegler et al., 2012; 1569-9048/© 2014 Elsevier B.V. All rights reserved. Dungan et al., 2009) and stimulation of adipose tissue lipolysis (Jaworski et al., 2007; Lafontan and Langin, 2009; Zechner et al., 2009; Bickel et al., 2009). However, the autonomic nervous system blockade with hexamethonium did not reverse insulin resistance induced by acute IH in mice (Iiyori et al., 2007) questioning the role of the sympathetic nervous system in insulin resistance during IH. "
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    ABSTRACT: Obstructive sleep apnea causes intermittent hypoxia (IH) and is associated with insulin resistance and type 2 diabetes. IH increases plasma catecholamine levels, which may increase insulin resistance and suppress insulin secretion. The objective of this study was to determine if adrenal medullectomy (MED) prevents metabolic dysfunction in IH. MED or sham surgery was performed in 60 male C57BL/6J mice, which were then exposed to IH or control conditions (intermittent air) for 6 weeks. IH increased plasma epinephrine and norepinephrine levels, increased fasting blood glucose and lowered basal and glucose-stimulated insulin secretion. MED decreased baseline epinephrine and prevented the IH induced increase in epinephrine, whereas the norepinephrine response remained intact. MED improved glucose tolerance in mice exposed to IH, attenuated the impairment in basal and glucose-stimulated insulin secretion, but did not prevent IH-induced fasting hyperglycemia or insulin resistance. We conclude that the epinephrine release from the adrenal medulla during IH suppresses insulin secretion causing hyperglycemia.
    Respiratory Physiology & Neurobiology 08/2014; 203. DOI:10.1016/j.resp.2014.08.018 · 1.97 Impact Factor
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