Role of adipose tissue lipolysis and adipose triglyceride lipase in non-alcoholic fatty liver disease progression
Event details
| Date | 10.04.2014 |
| Hour | 10:30 › 11:30 |
| Speaker | Dr. Pooja JHA, Medical University of Vienna and Medical University of Graz (AT) |
| Location | |
| Category | Conferences - Seminars |
SEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION ALLIANCE (LIMNA)
Mechanisms underlying the pathogenesis of NAFLD and its progression to steatohepatitis (NASH) are poorly understood. Increased fatty acid (FA) flux from adipose tissue to the liver and impaired FA signaling in liver may be involved. Since ATGL is a key intracellular lipase involved in hydrolysis of stored fat and lipid partitioning, we aimed to explore the role of ATGL in mouse models of NAFLD and NASH.
Using methionine-choline-deficient (MCD) diet to induce NASH in ob/ob mice we showed that (i) increased ATGL and hormone-sensitive lipase (HSL) activity in adipose tissue and (ii) decreased ATGL activity in liver mediate loss of adipose tissue followed by hepatic steatosis and inflammation. We next used mice deficient in ATGL and HSL to induce steatohepatitis and endotoxemia. In both these models, we showed that ATGL plays an antiinflammatory role in liver via activation of PPARα. We found that ATGL also plays an important role in circadian regulation of hepatic lipid metabolism, in particular at zeitgeber time (ZT)12 when PPARα expression is at its peak in liver. In support of this hypothesis, we found that FA profile of PPARα ligands were attenuated in ATGL-KO mice at this timepoint. Our findings fuel optimism that ATGL could represent an exciting therapeutic target for metabolic and inflammatory liver diseases.
Bio: Dr. Jha is a Postdoctoral Fellow at the Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria, and at the Institute of Pathology, Medical University of Graz, Austria
Mechanisms underlying the pathogenesis of NAFLD and its progression to steatohepatitis (NASH) are poorly understood. Increased fatty acid (FA) flux from adipose tissue to the liver and impaired FA signaling in liver may be involved. Since ATGL is a key intracellular lipase involved in hydrolysis of stored fat and lipid partitioning, we aimed to explore the role of ATGL in mouse models of NAFLD and NASH.
Using methionine-choline-deficient (MCD) diet to induce NASH in ob/ob mice we showed that (i) increased ATGL and hormone-sensitive lipase (HSL) activity in adipose tissue and (ii) decreased ATGL activity in liver mediate loss of adipose tissue followed by hepatic steatosis and inflammation. We next used mice deficient in ATGL and HSL to induce steatohepatitis and endotoxemia. In both these models, we showed that ATGL plays an antiinflammatory role in liver via activation of PPARα. We found that ATGL also plays an important role in circadian regulation of hepatic lipid metabolism, in particular at zeitgeber time (ZT)12 when PPARα expression is at its peak in liver. In support of this hypothesis, we found that FA profile of PPARα ligands were attenuated in ATGL-KO mice at this timepoint. Our findings fuel optimism that ATGL could represent an exciting therapeutic target for metabolic and inflammatory liver diseases.
Bio: Dr. Jha is a Postdoctoral Fellow at the Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria, and at the Institute of Pathology, Medical University of Graz, Austria
Practical information
- Informed public
- Free
Organizer
- Kristina Schoonjans and Johan Auwerx (for the LIMNA Alliance)
Contact
- Johan Auwerx
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