ORCID Profile
0000-0002-6666-6871
Current Organisation
University of Oxford
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Publisher: Public Library of Science (PLoS)
Date: 08-09-2017
Publisher: American Physiological Society
Date: 04-2019
DOI: 10.1152/AJPENDO.00365.2018
Abstract: The liver is a critical tissue for maintaining glucose, fatty acid, and cholesterol homeostasis. Primary hepatocytes represent the gold standard for studying the mechanisms controlling hepatic glucose, lipid, and cholesterol metabolism in vitro. However, access to primary hepatocytes can be limiting, and therefore, other immortalized hepatocyte models are commonly used. Here, we describe substrate metabolism of cultured AML12, IHH, and PH5CH8 cells, hepatocellular carcinoma-derived HepG2s, and primary mouse hepatocytes (PMH) to identify which of these cell lines most accurately phenocopy PMH basal and insulin-stimulated metabolism. Insulin-stimulated glucose metabolism in PH5CH8 cells, and to a lesser extent AML12 cells, responded most similarly to PMH. Notably, glucose incorporation in HepG2 cells were 14-fold greater than PMH. The differences in glucose metabolic activity were not explained by differential protein expression of key regulators of these pathways, for ex le glycogen synthase and glycogen content. In contrast, fatty acid metabolism in IHH cells was the closest to PMHs, yet insulin-responsive fatty acid metabolism in AML12 and HepG2 cells was most similar to PMH. Finally, incorporation of acetate into intracellular-free cholesterol was comparable for all cells to PMH however, insulin-stimulated glucose conversion into lipids and the incorporation of acetate into intracellular cholesterol esters were strikingly different between PMHs and all tested cell lines. In general, AML12 cells most closely phenocopied PMH in vitro energy metabolism. However, the cell line most representative of PMHs differed depending on the mode of metabolism being investigated, and so careful consideration is needed in model selection.
Publisher: Oxford University Press (OUP)
Date: 30-10-2018
DOI: 10.1093/IJE/DYX216
Abstract: Verbal autopsy (VA) is a method that determines the cause of death by interviewing a relative of the deceased about the events occurring before the death, in regions where medical certification of cause of death is incomplete. This paper aims to review the ethical standards reported in peer-reviewed VA studies. A systematic review of Medline and Ovid was conducted by two independent researchers. Data were extracted and analysed for articles based on three key areas: Institutional Review Board (IRB) clearance and consenting process data collection and management procedures, including: time between death and interview training and education of interviewer, confidentiality of data and data security and declarations of funding and conflict of interest. The review identified 802 articles, of which 288 were included. The review found that 48% all the studies reported having IRB clearance or obtaining consent of participants. The interviewer training and education levels were reported in 62% and 21% of the articles, respectively. Confidentiality of data was reported for 14% of all studies, 18% did not report the type of respondent interviewed and 51% reported time between death and the interview for the VA. Data security was reported in 8% of all studies. Funding was declared in 63% of all studies and conflict of interest in 42%. Reporting of all these variables increased over time. The results of this systematic review show that although there has been an increase in ethical reporting for VA studies, there still remains a large gap in reporting.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2019
DOI: 10.1158/1541-7786.MCR-18-0347
Abstract: Extracellular-derived FAs are primary building blocks for complex lipids and heterogeneity in FA metabolism exists in prostate cancer that can influence tumor cell behavior.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.YEXCR.2017.07.015
Abstract: Annexin A6 (AnxA6) has been implicated in the regulation of endo-/exocytic pathways, cholesterol transport, and the formation of multifactorial signaling complexes in many different cell types. More recently, AnxA6 has also been linked to triglyceride storage in adipocytes. Here we investigated the potential role of AnxA6 in fatty acid (FA) - induced lipid droplet (LD) formation in hepatocytes. AnxA6 was associated with LD from rat liver and HuH7 hepatocytes. In oleic acid (OA) -loaded HuH7 cells, substantial amounts of AnxA6 bound to LD in a Ca
Publisher: Cold Spring Harbor Laboratory
Date: 10-03-2023
DOI: 10.1101/2023.03.09.531813
Abstract: Fatty liver is characterised by the expansion of lipid droplets and is associated with the development of many metabolic diseases, including insulin resistance, dyslipidaemia and cardiovascular disease. We assessed the morphology of hepatic lipid droplets and performed quantitative proteomics in lean, glucose-tolerant mice compared to high-fat diet (HFD) fed mice that displayed hepatic steatosis and glucose intolerance as well as high-starch diet (HStD) fed mice who exhibited similar levels of hepatic steatosis but remained glucose tolerant. Both HFD and HStD-fed mice had more and larger lipid droplets than Chow-fed animals. We observed striking differences in liver lipid droplet proteomes of HFD and HStD-fed mice compared to Chow-fed mice, with fewer differences between HFD and HStD. Taking advantage of our diet strategy, we identified a fatty liver lipid droplet proteome consisting of proteins common in HFD- and HStD-fed mice. Likewise, a proteome associated with glucose tolerance that included proteins common in Chow and HStD but not HFD-fed mice was identified. Notably, glucose intolerance was associated with changes in the ratio of adipose triglyceride lipase (ATGL) to perilipin 5 (PLIN5) in the lipid droplet proteome, suggesting dysregulation of neutral lipid homeostasis in glucose-intolerant fatty liver, which supports bioactive lipid synthesis and impairs hepatic insulin action. We conclude that our novel dietary approach uncouples ectopic lipid burden from insulin resistance-associated changes in the hepatic lipid droplet proteome.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Shilpa Nagarajan.