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| ATGL 脂肪甘油三酯脂酶（Adipose Triglyceride Lipase，ATGL）是一个代谢综合征标示物 |
脂肪组织是脊椎类生物最重要的能量储存库。这个脂肪库的维持是一个动态平衡调节，即脂肪的合成（成脂）和脂肪的分解（异脂）之间的动态平衡。任何因素引起这一动态平衡的紊乱或是失平衡，导致代谢紊乱、代谢综合征、肥胖和二型糖尿病的发生和发展。游离脂肪酸从脂肪组织的释放依赖于脂肪酶的水解活性。过去一般认为，激素敏感的脂肪酶是主管细胞脂肪分解的关键酶。但是，敲除激素敏感的脂肪酶基因的小鼠， 并没有发生游离脂肪酸生成的障碍。提示激素敏感的脂肪酶不是体内决定脂肪分解和能量代谢的关键酶。奥地利的科学家研究结构表明，脂肪甘油三酯脂肪酶才是影响细胞游离脂肪酸代谢和能量稳态的关键限速酶，推测他可能是今后研究开发代谢综合征和二型糖尿病的新药的靶点。此研究结果显示，脂肪甘油三酯脂肪酶基因敲除小鼠，丧失了该酶生物活性，结果造成脂肪组织增生和大量甘油三酯在多种组织中堆积。过量脂肪在心脏附着和堆积，导致心脏功能下降，和动物未成年的死亡。防御性冷适应行为提示该酶催化游离脂肪酸燃烧以维持机体温度衡态。降低脂肪甘油三酯脂肪酶意依赖性游离脂肪酸可利用度，导致糖利用增加，糖耐量和胰岛素敏感度增加。这些结果显示脂肪甘油三酯脂肪酶是主管细胞内脂肪分解代谢和能量稳态的限速酶。
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010-81786244； 010-
81786624 |
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Info@adipobiotech.com |
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www.AdipoBiotech.com |
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| Product Name |
Catalog No. |
Size |
Price |
| 脂肪甘油三酯脂肪酶（ATGL）蛋白质印迹试剂盒 |
W00576-01 |
5次 |
500 USD |
| 脂肪甘油三酯脂肪酶（ATGL）免疫组化试剂盒 |
IHC00576-01 |
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550 USD |
| Anti-human ATGL MAB 单克隆抗体 |
A00576-02-100 |
100 ul |
300 USD |
| Anti-human ATGL Antibody 兔多克隆抗体 |
A00576-03-100 |
100 ul |
300 USD |
| Anti -Adipose Triglyceride Lipase （ATGL）(
Rat, Mouse) Antibody |
A00576-06-100 |
100 ul |
300 USD |
| Adipose Triglyceride Lipase （ATGL）, recombinant, mouse |
00576-06-100 |
100 ug |
250 USD |
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| Immunohistochemical analysis of NIH/3T3-L1 cells undifferentiated (left) or differentiated (right), showing induced staining of adipocytes, using ATGL (A00576-02) mAb. |
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| Confocal immunofluorescent analysis of 3T3-L1 cells, using ATGL (A00576-02) mAb (red) showing cytoplasmic localization in differentiated cells. Lipid droplets have been labeled with BODIPY 493/503 (green). Blue pseudocolor = DRAQ5? (fluorescent DNA dye) |
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| Immunohistochemical analysis of paraffin-embedded mouse lung, showing staining specific to adipocytes, using ATGL (A00576-02) mAb |
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| Confocal immunofluorescent analysis of 3T3-L1 cells using ATGL Antibody [目录号A00576-03] (red) showing cytoplasmic localization in differentiated cells. Lipid droplets have been labeled with BODIPY 493/503 (green). Blue pseudocolor = DRAQ5? (fluorescent DNA dye). |
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| Immunohistochemical analysis of paraffin-embedded mouse lung, showing specific staining of fat, using ATGL Antibody [目录号A00576-03]. |
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| Immunohistochemical analysis of paraffin-embedded NIH/3T3-L1 cells undifferentiated (left) or differentiated (right), showing induced staining in adipocytes, using ATGL Antibody [目录号A00576-03]. |
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Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase |
| Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis. |
| Haemmerle G, et al. Science. 2006 May 5;312(5774):734-7. |
| Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state |
| J Clin Endocrinol Metab. 2007 Jun;92(6):2292-9. Epub 2007 Mar 13 |
Adipocyte triglyceride lipase expression in human obesity |
| We have investigated the gene and protein expression of adipose triglyceride lipase (ATGL) and triglyceride (TG) lipase activity from subcutaneous and visceral adipose tissue of lean and obese subjects. Visceral and subcutaneous adipose tissue was obtained from 16 age-matched lean and obese subjects during abdominal surgery. Tissues were analyzed for mRNA expression of lipolytic enzymes by real-time quantitative PCR. ATGL protein content was assessed by Western blot and TG lipase activity by radiometric assessment. Subcutaneous and visceral adipose tissue of obese subjects had elevated mRNA expression of PNPLA2 (ATGL) and other lipases including PNPLA3, PNPLA4, CES1, and LYPLAL1 (P < 0.05). Surprisingly, ATGL protein expression and TG lipase activity were reduced in subcutaneous adipose tissue of obese subjects. Immunoprecipitation of ATGL reduced total TG lipase activity in adipose lysates by 70% in obese and 83% in lean subjects. No significant differences in the ATGL activator CGI-58 mRNA levels (ABHD5) were associated with obesity. These data demonstrate that ATGL is important for efficient TG lipase activity in humans. They also demonstrate reduced ATGL protein expression and TG lipase activity despite increased mRNA expression of ATGL and other novel lipolytic enzymes in obesity. The lack of correlation between ATGL protein content and in vitro TG lipase activity indicates that small decrements in ATGL protein expression are not responsible for the reduction in TG lipase activity observed here in obesity, and that posttranslational modifications may be important. |
| Gregory R. Steinberg et al. Am J Physiol Endocrinol Metab 293: E958-E964, 2007. First published July 3, 2007; |
Adipose Triglyceride Lipase and Hormone-sensitive Lipase Are the Major Enzymes in Adipose Tissue Triacylglycerol Catabolism |
The mobilization of free fatty acids from adipose triacylglycerol (TG) stores requires the activities of triacylglycerol lipases. In this study, we demonstrate that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major enzymes contributing to TG breakdown in in vitro assays and in organ cultures of murine white adipose tissue (WAT). To differentiate between ATGL- and HSL-specific activities in cytosolic preparations of WAT and to determine the relative contribution of these TG hydrolases to the lipolytic catabolism of fat, mutant mouse models lacking ATGL or HSL and a mono-specific, small molecule inhibitor for HSL (76-0079) were used. We show that 76-0079 had no effect on TG catabolism in HSL-deficient WAT but, in contrast, essentially abolished free fatty acid mobilization in ATGL-deficient fat. CGI-58, a recently identified coactivator of ATGL, stimulates TG hydrolase activity in wild-type and HSL-deficient WAT but not in ATGL-deficient WAT, suggesting that ATGL is the sole target for CGI-58-mediated activation of adipose lipolysis. Together, ATGL and HSL are responsible for more than 95% of the TG hydrolase activity present in murine WAT. Additional known or unknown lipases appear to play only a quantitatively minor role in fat cell lipolysis.
Martina Schweiger et al. J. Biol. Chem., Vol. 281, Issue 52, 40236-40241, December 29, 2006 |
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| Expression pattern of ATGL transcript and localization of ATGL protein. A: ATGL transcript level in a panel of murine tissues. Total RNA (5 μg) from indicated mouse tissues were analyzed by Northern blot using murine ATGL cDNA probe. 3T3-L1 adipocyte RNA was loaded for positive control (Adipocyte). EtBr staining of rRNA was used as gel-loading control. B: expression of ATGL transcript in tissues of wild-type (wt) and obese (ob/ob) mice. Subcutaneous (SC) and epididymal adipose tissue (EP), liver (L), and kidney (K) RNA was isolated from 8-wk-old wt C57BL/6 and ob/ob mice and subjected to Northern blot hybridization for ATGL and 36B4 levels, quantitatated by PhosphorImager analysis, and ATGL transcript level for each sample normalized against its 36B4 control to correct for possible variations in sample loading. Data represent normalized ATGL means ± SD from wt mice (n = 4 for SC, n = 5 for EP, n = 6 for liver and kidney) or ob/ob mice (n = 6 for SC, n = 7 for EP, liver, kidney) and were analyzed by single-factor ANOVA (*P < 0.05, **P < 0.005, #P < 0.001). C: ATGL expression in WAT of mouse strains. EP and SC adipose tissue RNA was harvested from SM/J (S, n = 5) and NZB/BINJ (N, n = 6) male mice and analyzed as described in B. Individual animals are represented by triangles, with horizontal line indicating group mean, which was not significantly different between groups (P > 0.05). D: localization of ATGL protein in adipocytes. 3T3-L1 adipocytes were transfected with HA-tagged ATGL expression construct and then fixed and stained with anti-HA antibody followed by FITC-conjugated goat anti-rabbit IgG as described in MATERIALS AND METHODS. Images showed HA-tagged ATGL in green (top), lipid in red after Nile red staining (upper middle), and merged image in 3T3-L1 adipocytes (lower middle). ATGL expression in 3T3-L1 preadipocytes is also shown (bottom). Am J Physiol Endocrinol Metab 291: E115-E127, 2006; |
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| ATGL and HSL mRNA (panel A) and protein expression (panel B) before (black bars) and after (white bars) a 10-week hypocaloric diet. (A) The hypocaloric diet resulted in a significantly decreased ATGL and HSL mRNA expression (n=26; # P=0.001 and ## P=0.007, respectively). mRNA levels were quantified by RT-qPCR and normalized with 18S rRNA. (B) In line, a significantly decreased ATGL and HSL protein expression was observed after the diet (* P=0.04 and ** P=0.023, respectively). ATGL and HSL protein expression was quantified using Western blot and expression was related to the structural protein beta-actin. Before versus after using paired Student’s t-test statistics. Values are mean±SEM. Gregory R. Steinberg et al. Am J Physiol Endocrinol Metab 293: E958-E964, 2007. First published July 3, 2007; |
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ATGL and HSL mRNA and protein expression in subcutaneous adipose tissue of insulin sensitive (black bars, IS) versus insulin resistant (white bars, IR) overweight-obese subjects. (A) ATGL and HSL mRNA expression was significantly lower in IR (n=13) compared to IS (n=13) subjects (# P=0.006 and ## P=0.057, respectively). mRNA levels were quantified by RT-qPCR and normalized with 18S rRNA. (B) In line, ATGL and HSL protein expression was significantly lower in IR (n=22) compared to IS (n=22) subjects (* P=0.025 and ** P=0.001, respectively). ATGL and HSL protein expression was quantified using Western blot and expression was related to the structural protein beta-actin. IS versus IR using unpaired Student’s
t-test statistics. Values are mean±SEM. Gregory R. Steinberg et al. Am J Physiol Endocrinol Metab 293: E958-E964, 2007. First published July 3, 2007; |
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