LB-OR-5 THE ROLE OF ADIPOSE TRIGLYCERIDE LIPASE (ATGL) IN HUMAN ADIPOSE TISSUE LIPOLYSIS

2007 ◽  
Vol 8 (1) ◽  
pp. 228
Author(s):  
M. Schweiger ◽  
G. Schoiswohl ◽  
A. Lass ◽  
G. Haemmerle ◽  
R. Zechner ◽  
...  
2011 ◽  
Vol 96 (8) ◽  
pp. E1293-E1297 ◽  
Author(s):  
Thomas S. Nielsen ◽  
Mikkel H. Vendelbo ◽  
Niels Jessen ◽  
Steen B. Pedersen ◽  
Jens O. Jørgensen ◽  
...  

Abstract Context: Fasting and exercise are characterized by increased lipolysis, but the underlying mechanisms are not fully understood. Objective: The study was designed to test whether fasting and exercise affect mRNA and protein levels of adipose triglyceride lipase (ATGL) and G(0)/G(1) switch gene 2 (G0S2), a recently discovered ATGL inhibitor, in humans. Design and Participants: We studied eight healthy men (age, 25.5 ± 4.3 yr) for 6 h (a 4-h basal and a 2-h clamp period) on three occasions in a randomized crossover design: 1) in the basal state and after; 2) 72-h fasting; and 3) 1-h exercise (65% VO2max). Subcutaneous abdominal adipose tissue (AT) biopsies were taken at t = 30 and 270 min. Setting: The study was conducted at a university hospital research unit. Results: Circulating free fatty acids and GH were increased, and C-peptide was decreased by both fasting and exercise. During fasting, insulin failed to suppress free fatty acid levels, suggesting AT insulin resistance. ATGL protein was increased 44% (P < 0.001), and G0S2 mRNA and protein were decreased 56% (P = 0.02) and 54% (P = 0.01), respectively, after fasting, but both ATGL and G0S2 were unaffected by exercise. Protein levels of hormone-sensitive lipase and comparative gene identification-58 were unaffected throughout. Conclusions: We found increased AT content of ATGL and decreased protein and mRNA content of the ATGL inhibitor G0S2, suggesting increased ATGL activity during fasting, but not after short-term exercise. These findings are compatible with the notion that the ATGL-G0S2 complex is an important long-term regulator of lipolysis under physiological conditions such as fasting in humans.


Metabolism ◽  
2011 ◽  
Vol 60 (7) ◽  
pp. 1012-1020 ◽  
Author(s):  
Aiwei Yao-Borengasser ◽  
Vijayalakshmi Varma ◽  
Robert H. Coker ◽  
Gouri Ranganathan ◽  
Bounleut Phanavanh ◽  
...  

Nitric Oxide ◽  
2012 ◽  
Vol 27 ◽  
pp. S21
Author(s):  
Karoline Dörffel ◽  
Sarah Winkler ◽  
Günter Hämmerle ◽  
Rudolf Zechner ◽  
Alois Lametschwandtner ◽  
...  

2012 ◽  
Vol 13 (S1) ◽  
Author(s):  
Karoline Pail ◽  
Sarah Winkler ◽  
Gerald Wölkart ◽  
Günter Hämmerle ◽  
Rudolf Zechner ◽  
...  

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Michael J. Trites ◽  
Robin D. Clugston

AbstractThe ability of mammals to store and draw on fat reserves has been a driving force throughout evolution in an environment with intermittent nutrient availability. The discovery of adipose triglyceride lipase (ATGL) as a triglyceride lipase provided a heightened understanding of the mechanisms governing mobilization of fat reserves from adipose tissue. ATGL catalyses the initial step in adipose triglyceride lipolysis, working in concert with other enzymes to mobilize triglyceride for energy production. In addition to the role of ATGL in adipose tissue triglyceride mobilization, ATGL plays crucial roles in regulating lipid homeostasis in other tissues. These roles have been characterized primarily using transgenic mice with tissue-specific ATGL ablation. For example, the global ATGL knockout induces a severe cardiac defect that results in premature mortality that is mimicked by inducible cardiomyocyte-specific ATGL knockout. Global- and adipose-specific ATGL ablation induces a whole-body shift from lipid metabolism to glucose metabolism to satisfy metabolic demand primarily facilitated by an increase in glucose uptake by skeletal muscle. Generation of liver-specific ATGL knockouts has implicated hepatic lipolysis as a critical component of normal liver function. Analysis of β-cell ATGL knockouts implicates the necessity of pancreatic ATGL in insulin secretion. The objective of this review is to discuss the contributions of ATGL to systemic lipid- and glucose-homeostasis discovered through the study of transgenic mice.


2013 ◽  
Vol 14 (S1) ◽  
Author(s):  
Marion Mussbacher ◽  
Karoline Pail ◽  
Gerald Wölkart ◽  
Günter Hämmerle ◽  
Alois Lametschwandtner ◽  
...  

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Martina Schweiger ◽  
Matthias Romauch ◽  
Renate Schreiber ◽  
Gernot F. Grabner ◽  
Sabrina Hütter ◽  
...  

Abstract Elevated circulating fatty acids (FAs) contribute to the development of obesity-associated metabolic complications such as insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). Hence, reducing adipose tissue lipolysis to diminish the mobilization of FAs and lower their respective plasma concentrations represents a potential treatment strategy to counteract obesity-associated disorders. Here we show that specific inhibition of adipose triglyceride lipase (Atgl) with the chemical inhibitor, Atglistatin, effectively reduces adipose tissue lipolysis, weight gain, IR and NAFLD in mice fed a high-fat diet. Importantly, even long-term treatment does not lead to lipid accumulation in ectopic tissues such as the skeletal muscle or heart. Thus, the severe cardiac steatosis and cardiomyopathy that is observed in genetic models of Atgl deficiency does not occur in Atglistatin-treated mice. Our data validate the pharmacological inhibition of Atgl as a potentially powerful therapeutic strategy to treat obesity and associated metabolic disorders.


2020 ◽  
Vol 21 (21) ◽  
pp. 8289
Author(s):  
Mari T. Kaartinen ◽  
Mansi Arora ◽  
Sini Heinonen ◽  
Aila Rissanen ◽  
Jaakko Kaprio ◽  
...  

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.


2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
John N. Fain

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFβ1, TNFα, IL-1β, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans.


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