Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease

Zhang, Xuelin; Wang, Yang; Liu, Pingsheng

doi:10.1007/s13238-016-0327-9

Cited by 29 publications

(23 citation statements)

References 92 publications

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“…HSD17B13 was previously reported to be localized to the LDs in mouse (8) and human (9) hepatocytes. A role of LD-associated proteins in the formation and expansion of LDs as well as in NAFLD progression has been reported in multiple studies (38)(39)(40)(41). Consistent with these observations, we observed increased expression of PLIN2, one of the LD proteins, in hepatic tissues of HSD17B13KO mice.…”

Section: Discussionsupporting

confidence: 92%

Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice

Adam

Heikelä

Sobolewski³

et al. 2018

FASEB j.

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Hydroxysteroid (17β) dehydrogenases (HSD17Bs) form an enzyme family characterized by their ability to catalyze reactions in steroid and lipid metabolism. In the present study, we characterized the phenotype of HSD17B13-knockout (HSD17B13KO) mice deficient in Hsd17b13. In these studies, hepatic steatosis was detected in HSD17B13KO male mice, indicated by histologic analysis and by the increased triglyceride concentration in the liver, whereas reproductive performance and serum steroid concentrations were normal in HSD17B13KO mice. In line with these changes, the expression of key proteins in fatty acid synthesis, such as FAS, acetyl-CoA carboxylase 1, and SCD1, was increased in the HSD17B13KO liver. Furthermore, the knockout liver showed an increase in 2 acylcarnitines, suggesting impaired mitochondrial β-oxidation in the presence of unaltered malonyl CoA and AMPK expression. The glucose tolerance did not differ between wild-type and HSD17B13KO mice in the presence of lower levels of glucose 6-phosphatase in HSD17B13KO liver compared with wild-type liver. Furthermore, microgranulomas and increased portal inflammation together with up-regulation of immune response genes were observed in HSD17B13KO mice. Our data indicate that disruption of Hsd17b13 impairs hepatic-lipid metabolism in mice, resulting in liver steatosis and inflammation, but the enzyme does not play a major role in the regulation of reproductive functions.-Adam, M., Heikelä, H., Sobolewski, C., Portius, D., Mäki-Jouppila, J., Mehmood, A., Adhikari, P., Esposito, I., Elo, L. L., Zhang, F.-P., Ruohonen, S. T., Strauss, L., Foti, M., Poutanen, M. Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice.

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Section: Discussionsupporting

confidence: 92%

Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice

Adam

Heikelä

Sobolewski³

et al. 2018

FASEB j.

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“…The findings that neutral lipids occupy approximately 5-16% of bovine luteal tissue area is in agreement with other studies examining LD to luteal cell area or volume (27,28,43). In contrast, other tissues rarely contain the same amount of neutral lipids, except during pathological situations (8)(9)(10)(11). Likely, the area occupied by LDs in steroidogenic cells is even greater since luteal endothelial cells account for nearly 50% of luteal tissue (44) but rarely contain LDs (45).…”

Section: Discussionsupporting

confidence: 89%

Composition of the Lipid Droplets of the Bovine Corpus Luteum

Talbott

Plewes

Krause

et al. 2020

Preprint

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Phosphatidylinositol; PLIN, perilipin; PNS, post-nuclear supernatant; PNS-LD, post-nuclear supernatant depleted of lipid droplet; PS, Phosphatidylserine; SEM, standard error of the mean; SM, Sphingomyelin; SB, sphingoid bases; SOAT1, Sterol O-acyltransferase; STAR, steroidogenic acute regulatory protein; TC; theca cell; TEM, Transmission electron microscopy 2. Abstract (199/200 words)Establishment and maintenance of pregnancy is dependent on progesterone synthesized by luteal tissue in the ovary.Our objective was to identify the characteristics of lipid droplets (LDs) in ovarian steroidogenic cells. We hypothesized that LDs are a major feature of steroidogenic luteal cells and store cholesteryl esters. Bovine luteal tissue was used for whole tissue analysis. Further analyses were performed on isolated ovarian steroidogenic cells: granulosa and theca cells of the follicle, and small/large luteal cells. Isolated luteal LDs were collected for lipid/protein analyses. Luteal tissue contained perilipins 2/3/5, hormone-sensitive lipase and abhydrolase domain containing 5. Luteal tissue was enriched in TGs compared to other tissues, except of adipose tissue. Large and small luteal cells were distinguished from follicular cells by the presence of LDs and LD-associated proteins. Furthermore, LDs from large luteal cells were numerous and small; whereas, LDs from small luteal cells were large and less numerous. Isolated LDs contained nearly all of the TGs and cholesteryl esters present in luteal tissue. Isolated luteal LDs were composed primarily of TG, with lesser amounts of cholesteryl esters, diglyceride and other phospholipids. Bovine luteal tissue LDs are distinct from LDs in other bovine tissues, including follicular steroidogenic cells.

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“…In contrast to candidate-gene studies, GWAS are particularly useful for the identification of novel genes associated with diseases that otherwise would have not been considered as candidates due to a limited knowledge of their function. To date, there is compelling evidence of the association of variants in the Patatin-like phospholipase domain containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) genes, which are both involved in liver fat retention through lipid droplet remodelling and very-low density lipoprotein (VLDL) secretion, and NAFLD susceptibility and progression to NASH [ 119 , 120 , 121 , 122 , 123 ]. On the other hand, environmental factors and their impact on pathways involved in the pathogenesis of disease can be assessed by other omics analysis.…”

Section: Application Of Omics Technologies In Liver Diseasesmentioning

confidence: 99%

“…While transcriptomics allows the identification of alterations in gene expression, proteomics can be used to monitor changes in protein expression and post-translational modifications at different stages of disease progression. Proteomic studies of NAFLD have revealed 34 candidate biomarkers in liver and serum [ 119 , 122 , 126 ]. Gene or protein expression changes do not always correspond to phenotypic alterations because they operate on a markedly different time scales.…”

Section: Application Of Omics Technologies In Liver Diseasesmentioning

confidence: 99%

Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease

et al. 2017

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Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH). Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed.

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Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease

Cited by 29 publications

References 92 publications

Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice

Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice

Composition of the Lipid Droplets of the Bovine Corpus Luteum

Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease

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