scholarly journals Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

2014 ◽  
Vol 289 (28) ◽  
pp. 19279-19293 ◽  
Author(s):  
Frits Mattijssen ◽  
Anastasia Georgiadi ◽  
Tresty Andasarie ◽  
Ewa Szalowska ◽  
Annika Zota ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Peroxisome Proliferator ◽  
Hepatic Triglyceride ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triglyceride Secretion

scholarly journals SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation

2016 ◽  
Vol 36 (7) ◽  
pp. 1180-1193 ◽  
Author(s):  
Nathan L. Price ◽  
Brandon Holtrup ◽  
Stephanie L. Kwei ◽  
Martin Wabitsch ◽  
Matthew Rodeheffer ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Target Genes ◽  
Adipocyte Differentiation ◽  
Regulatory Element ◽  
Critical Role ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

White adipose tissue (WAT) is essential for maintaining metabolic function, especially during obesity. The intronic microRNAs miR-33a and miR-33b, located within the genes encoding sterol regulatory element-binding protein 2 (SREBP-2) and SREBP-1, respectively, are transcribed in concert with their host genes and function alongside them to regulate cholesterol, fatty acid, and glucose metabolism. SREBP-1 is highly expressed in mature WAT and plays a critical role in promotingin vitroadipocyte differentiation. It is unknown whether miR-33b is induced during or involved in adipogenesis. This is in part due to loss of miR-33b in rodents, precludingin vivoassessment of the impact of miR-33b using standard mouse models. This work demonstrates that miR-33b is highly induced upon differentiation of human preadipocytes, along withSREBP-1. We further report that miR-33b is an important regulator of adipogenesis, as inhibition of miR-33b enhanced lipid droplet accumulation. Conversely, overexpression of miR-33b impaired preadipocyte proliferation and reduced lipid droplet formation and the induction of peroxisome proliferator-activated receptor γ (PPARγ) target genes during differentiation. These effects may be mediated by targeting of HMGA2, cyclin-dependent kinase 6 (CDK6), and other predicted miR-33b targets. Together, these findings demonstrate a novel role of miR-33b in the regulation of adipocyte differentiation, with important implications for the development of obesity and metabolic disease.

scholarly journals Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content

2002 ◽  
Vol 282 (2) ◽  
pp. E395-E401 ◽  
Author(s):  
Susanne Neschen ◽  
Irene Moore ◽  
Werner Regittnig ◽  
Chun Li Yu ◽  
Yanlin Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fish Oil ◽  
Oxidative Capacity ◽  
Fatty Acyl ◽  
Control Fish ◽  
Safflower Oil ◽  
Peroxisome Proliferator ◽  
Hepatic Triglyceride ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ceramide Content

To examine the mechanism by which fish oil protects against fat-induced insulin resistance, we studied the effects of control, fish oil, and safflower oil diets on peroxisomal content, fatty acyl-CoA, diacylglycerol, and ceramide content in rat liver and muscle. We found that, in contrast to control and safflower oil-fed rats, fish oil feeding induced a 150% increase in the abundance of peroxisomal acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in liver but lacked similar effects in muscle. This was paralleled by an almost twofold increase in hepatic peroxisome content (both P < 0.002 vs. control and safflower). These changes in the fish oil-fed rats were associated with a more than twofold lower hepatic triglyceride/diacylglycerol, as well as intramuscular triglyceride/fatty acyl-CoA, content. In conclusion, these data strongly support the hypothesis that n-3 fatty acids protect against fat-induced insulin resistance by serving as peroxisome proliferator-activated receptor-α ligands and thereby induce hepatic, but not intramuscular, peroxisome proliferation. In turn, an increased hepatic β-oxidative capacity results in lower hepatic triglyceride/diacylglycerol and intramyocellular triglyceride/fatty acyl-CoA content.

scholarly journals Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yun-Xia Zhu ◽  
Ming-Liang Zhang ◽  
Yuan Zhong ◽  
Chen Wang ◽  
Wei-Ping Jia
Keyword(s):  
Protein Expression ◽  
Hepatic Steatosis ◽  
Lipid Droplet ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Diet Induced Obesity ◽  
Elevated Expression ◽  
Ppar Agonists ◽  
Associated Proteins ◽  
Human Livers

Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγand PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγor PPARαagonist, pioglitazone or fenofibrate, respectively. Liver tissues fromdb/dbdiabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis.

scholarly journals Adipose Tissue Expression of the Lipid Droplet-Associating Proteins S3-12 and Perilipin Is Controlled by Peroxisome Proliferator-Activated Receptor- 

Diabetes ◽  
2004 ◽  
Vol 53 (5) ◽  
pp. 1243-1252 ◽  
Author(s):  
K. T. Dalen ◽  
K. Schoonjans ◽  
S. M. Ulven ◽  
M. S. Weedon-Fekjaer ◽  
T. G. Bentzen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Droplet ◽  
Tissue Expression ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Adipose Triglyceride Lipase protects the endocytosis of renal cells on a high fat diet in Drosophila

2020 ◽  
Author(s):  
Aleksandra Lubojemska ◽  
M. Irina Stefana ◽  
Lena Lampe ◽  
Azumi Yoshimura ◽  
Alana Burrell ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
High Fat Diet ◽  
Lipid Droplets ◽  
Adipose Triglyceride Lipase ◽  
Peroxisome Proliferator ◽  
Lipid Uptake ◽  
Renal Cells ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triglyceride Lipase

AbstractObesity-related renal lipotoxicity and chronic kidney disease (CKD) are prevalent pathologies with complex aetiologies. One hallmark of renal lipotoxicity is the ectopic accumulation of lipid droplets in kidney podocytes and in proximal tubule cells. Renal lipid droplets are observed in human CKD patients and in high-fat diet rodent models but their precise role remains unclear. Here, we establish a high-fat diet model in Drosophila that recapitulates renal lipid droplets and several other aspects of mammalian CKD. Cell-type specific genetic manipulations show that lipid can overflow from adipose tissue and is taken up by renal cells called nephrocytes. A high-fat diet drives nephrocyte lipid uptake via the multiligand receptor Cubilin, leading to the ectopic accumulation of lipid droplets. These nephrocyte lipid droplets correlate with ER and mitochondrial deficits, as well as with impaired macromolecular endocytosis, a key conserved function of renal cells. Nephrocyte knockdown of diglyceride acyltransferase 1 (DGAT1), overexpression of adipose triglyceride lipase (ATGL) and epistasis tests together reveal that fatty acid flux through the lipid droplet triglyceride compartment protects the ER, mitochondria and endocytosis of renal cells. Strikingly, boosting nephrocyte expression of the lipid droplet resident enzyme ATGL is sufficient to rescue high-fat diet induced defects in renal endocytosis. Moreover, endocytic rescue requires a conserved mitochondrial regulator, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α). This study demonstrates that lipid droplet lipolysis counteracts the harmful effects of a high-fat diet via a mitochondrial pathway that protects renal endocytosis. It also provides a genetic strategy for determining whether lipid droplets in different biological contexts function primarily to release beneficial or to sequester toxic lipids.

scholarly journals Capparis Spinosa Improves Non-Alcoholic Steatohepatitis Through Down-Regulating SREBP-1c and a PPARα-Independent Pathway in High-Fat Diet-Fed Rats

2021 ◽  
Author(s):  
Rasoul Akbari ◽  
Hamid Yaghooti ◽  
Mohammad Taha Jalali ◽  
Laya Sadat Khorsandi ◽  
Narges Mohammadtaghvaei
Keyword(s):  
Fatty Liver ◽  
Regulatory Element ◽  
Liver Steatosis ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Hepatic Triglyceride ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Steatohepatitis ◽  
Capparis Spinosa

Abstract Background: Non-alcoholic steatohepatitis (NASH) has become a global medical problem. Currently, there is no approved pharmacologic treatment for this condition. This study aimed to evaluate the ameliorative effects of Capparis spinosa (CS) on NASH in comparison to fenofibrate.Methods: An animal model of NASH was developed using a high-fat (HF) emulsion. Fatty liver rats were treated with aqueous extract of CS fruit or fenofibrate in parallel to the HF for six weeks. Animals were examined for weight gain, serum biochemistry, insulin sensitivity, hepatic triglyceride (TG) content, histopathological changes as well as gene expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), peroxisome proliferator-activated receptor α (PPARα) and Carnitine palmitoyltransferase I (CPT1) in liver.Results: Fasting blood sugar, insulin level, body and liver weight, activities of liver enzymes, hepatic triglyceride (TG) content as well as serum lipids were decreased following six weeks CS and fenofibrate treatments compared to the HF administration alone. Histopathological examinations also showed that liver steatosis, inflammation and hepatic fibrosis were markedly attenuated in response to CS and fenofibrate interventions. At the molecular level, CS treatment down-regulated SREBP1c, ACC and up-regulated CPT1 expression, but did not show a significant effect on PPARα. In contrast, fenofibrate treatment induced the expression of all studied genes in fatty liver rats.Conclusions: These findings indicated the favorable therapeutic effects of CS fruit extract on liver damages associated with NASH. The beneficial effects of CS on lipid accumulation and steatosis were comparable to those of fenofibrate.

scholarly journals The Lipid Droplet-Associated Protein Adipophilin Is Expressed in Human Trophoblasts and Is Regulated by Peroxisomal Proliferator-Activated Receptor-γ/Retinoid X Receptor

2003 ◽  
Vol 88 (12) ◽  
pp. 6056-6062 ◽  
Author(s):  
Ibrahim Bildirici ◽  
Cheong-Rae Roh ◽  
W. Timothy Schaiff ◽  
Beth M. Lewkowski ◽  
D. Michael Nelson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Droplet ◽  
Fatty Acid Uptake ◽  
Cellular Fatty Acid ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Acid Uptake ◽  
Lipid Uptake ◽  
Peroxisome Proliferator Activated Receptor ◽  
Associated Proteins

Abstract Uptake and transplacental transfer of fatty acids is essential for fetal development. Human adipophilin and its murine ortholog adipocyte differentiation-related protein are lipid droplet-associated proteins that are implicated in cellular fatty acid uptake in adipocytes. The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) stimulates lipid uptake by adipocytes and enhances differentiation of placental trophoblasts. We therefore hypothesized that adipophilin is expressed in human trophoblasts and that its expression is regulated by PPARγ. We initially determined that adipophilin is expressed in human villous trophoblasts and that adipophilin expression is enhanced during differentiation of cultured primary term human trophoblasts. We also found that exposure of cultured human trophoblasts to the PPARγ ligand troglitazone resulted in a concentration-dependent increase in adipophilin expression. We observed a similar increase with LG268, a ligand for retinoid X receptor (RXR), the heterodimeric partner of PPARγ. Lastly, we demonstrated that ligand-activated PPARγ and RXR stimulated the transcriptional activity of adipophilin promoter in CV-1 cells and in the placental JEG3 cell line. We conclude that the expression of adipophilin is enhanced during trophoblast differentiation and is up-regulated by ligand-activated PPARγ/RXR. Enhanced adipophilin expression may contribute to fatty acid uptake by the placenta.

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