Chronic treatment with the modified Longdan Xiegan Tang attenuates olanzapine-induced fatty liver in rats by regulating hepatic de novo lipogenesis and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c, PPAR-alpha and AMPK-alpha

2019 ◽  
Vol 232 ◽  
pp. 176-187 ◽  
Author(s):  
Liying Ren ◽  
Dongmei Sun ◽  
Xia Zhou ◽  
Yifan Yang ◽  
Xiaoqian Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Liver ◽  
Chronic Treatment ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Beta Oxidation ◽  
Ppar Alpha ◽  
Fatty Acid Beta Oxidation

Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model

2006 ◽  
Vol 291 (6) ◽  
pp. G1011-G1019 ◽  
Author(s):  
Ian P. J. Alwayn ◽  
Charlotte Andersson ◽  
Sang Lee ◽  
Danielle A. Arsenault ◽  
Bruce R. Bistrian ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Essential Fatty Acid ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Resonance Spectroscopy ◽  
Liver Triglyceride ◽  
Triglyceride Accumulation ◽  
Tnf Α

Steatosis is a prominent feature of nonalcoholic fatty liver disease and a potential promoter of inflammation. Injury leading to cirrhosis is partly mediated by dysregulation of matrix protein turnover. Matrix metalloproteinase (MMP) inhibitors protect mice from lethal TNF-α induced liver injury. We hypothesized that Marimastat, a broad-spectrum MMP and TNF-α converting enzyme (TACE) inhibitor, might modulate this injury through interruption of inflammatory pathways. Triglyceride and phospholipid levels (liver, serum) and fatty acid profiles were used to assess essential fatty acid status and de novo lipogenesis as mechanisms for hepatic steatosis. Mice receiving a fat-free, high-carbohydrate diet (HCD) for 19 days developed severe fatty liver infiltration, demonstrated by histology, magnetic resonance spectroscopy, and elevated liver function tests. Animals receiving HCD plus Marimastat (HCD+MAR) were comparable to control animals. Increased tissue levels of peroxisome proliferator activated receptor-α (PPAR-α), higher levels of serum IL-6, and decreased levels of serum TNF-α receptor II were also seen in the HCD+MAR group compared with HCD-only. In addition, there was increased phosphorylation, and likely activation, of PPAR-α in the HCD+MAR group. PPAR-α is a transcription factor involved in β-oxidation of fatty acids, and IL-6 is a hepatoprotective cytokine. Liver triglyceride levels were higher and serum triglyceride and phospholipid levels lower with HCD-only but improved with Marimastat treatment. HCD-only and HCD+MAR groups were essential fatty acid deficient and had elevated rates of de novo lipogenesis. We therefore conclude that Marimastat reduces liver triglyceride accumulation by increasing fat oxidation and/or liver clearance of triglycerides. This may be related to increased expression and activation of PPAR-α or IL-6, respectively.

scholarly journals Hepatic Deletion of Mboat7 (Lpiat1) Causes Activation of SREBP-1c and Fatty Liver

2020 ◽  
pp. jlr.RA120000856 ◽  
Author(s):  
Mingfeng Xia ◽  
Preethi Chandrasekaran ◽  
Shunxing Rong ◽  
Xiaorong Fu ◽  
Matthew A. Mitsche
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Fatty Liver ◽  
Acid Composition ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Fatty Acid Content ◽  
De Novo Lipogenesis ◽  
Knock Out ◽  
Polyunsaturated Fatty Acid Content

Genetic variants that increase the risk of fatty liver disease (FLD) and cirrhosis have recently been identified in the proximity of membrane bound O-acyltransferase domain-containing 7 (MBOAT7).  To elucidate the link between these variants and FLD we characterized Mboat7 liver-specific knock-out mice (Mboat7-LSKO).  Chow-fed Mboat7-LSKO mice developed fatty livers and associated liver injury.  Lipidomic analysis of liver using mass spectrometry revealed a pronounced reduction in 20-carbon polyunsaturated fatty acid content in phosphatidylinositols (PIs), but not in other phospholipids. The change in fatty acid composition of PIs in these mice was associated with a marked increase in de novo lipogenesis due to activation of SREBP-1c, a transcription factor that coordinates the activation of genes encoding enzymes in the fatty acid biosynthesis pathway. Hepatic removal of both SREBP cleavage activating protein (Scap) and Mboat7 normalized hepatic triglycerides relative to Scap only hepatic knock-out showing increased SREBP-1c processing is required for Mboat7 induced steatosis.  This study reveals a clear relationship between PI fatty acid composition and regulation of hepatic fat synthesis and delineates the mechanism by which mutations in MBOAT7 cause hepatic steatosis.

scholarly journals A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1822
Author(s):  
Christian von Loeffelholz ◽  
Sina M. Coldewey ◽  
Andreas L. Birkenfeld
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mammalian Cells ◽  
De Novo ◽  
Adenosine Monophosphate ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

scholarly journals The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results

2010 ◽  
Vol 33 (5) ◽  
pp. 479-494 ◽  
Author(s):  
Ronald J. A. Wanders ◽  
Jos P. N. Ruiter ◽  
Lodewijk IJlst ◽  
Hans R. Waterham ◽  
Sander M. Houten
Keyword(s):  
Fatty Acid ◽  
Neonatal Screening ◽  
Beta Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Fatty Acid Beta Oxidation
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