Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Journal article

Jackisch, L, Kumsaiyai, W, Moore, J.D, Al-Daghri, N, Kyrou, I, Barber, T.M, Randeva, H, Kumar, S, Tripathi, G and McTernan, P.G 2018. Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids. Diabetologia. https://doi.org/10.1007/s00125-018-4558-6
AuthorsJackisch, L, Kumsaiyai, W, Moore, J.D, Al-Daghri, N, Kyrou, I, Barber, T.M, Randeva, H, Kumar, S, Tripathi, G and McTernan, P.G
Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05). Our study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes.

Year2018
JournalDiabetologia
PublisherSpringer
ISSN0012186X
14320428
Digital Object Identifier (DOI)https://doi.org/10.1007/s00125-018-4558-6
Web address (URL)http://hdl.handle.net/10545/624102
hdl:10545/624102
Publication dates09 Feb 2018
Publication process dates
Deposited09 Aug 2019, 08:51
ContributorsUniversity of Warwick
Permalink -

https://repository.derby.ac.uk/item/95240/differential-expression-of-lp-pla2-in-obesity-and-type-2-diabetes-and-the-influence-of-lipids

Log in to edit
  • 49
    total views
  • 0
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Co-Culture of Gut Bacteria and Metabolite Extraction Using Fast Vacuum Filtration and Centrifugation
Guraka, A., Duff, R., Waldron, J., Tripathi, G. and Kermanizadeh, A. 2024. Co-Culture of Gut Bacteria and Metabolite Extraction Using Fast Vacuum Filtration and Centrifugation. Methods and Protocols. 7 (74), pp. 1-13. https://doi.org/10.3390/mps7050074
Drug induced liver injury - a 2023 update.
Allison, R., Guraka, A., Shawa, I., Tripathi, G., Moritz, W. and Kermanizadeh, A. 2023. Drug induced liver injury - a 2023 update. Journal of Toxicology and Environmental Health, Part B. 26 (8), pp. 1-26. https://doi.org/10.1080/10937404.2023.2261848
Design and Manufacture of One-Size-Fits-All Healthcare Face Shields for the NHS During the COVID-19 Pandemic
Gunputh, U., Williams, G., Leighton, A., Carter, W., Varasteh, H., Pawlik, M., Lu, Y., Sims, R., Lyons, M., Clementson, J., Tripathi, G., Nick Chambers, Matt Roe and Wood, P. 2022. Design and Manufacture of One-Size-Fits-All Healthcare Face Shields for the NHS During the COVID-19 Pandemic. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.4258668
Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions
Sreejesh Sreedharan, Zouganelis, G., Samantha J Drake, Gyanendra Tripathi and Ali Kermanizadeh 2022. Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions. Journal of Toxicology and Environmental Health, Part B: Critical Reviews. pp. 1-27. https://doi.org/10.1080/10937404.2022.2153456
PWE-001 field cancerisation theory in colorectal cancer (crc): what role do fibroblast growth factors have?
Patel, A, Williams, N, Nwokolo, C, Tripathi, G and Arasaradnam, R 2014. PWE-001 field cancerisation theory in colorectal cancer (crc): what role do fibroblast growth factors have? Gut. https://doi.org/10.1136/gutjnl-2014-307263.261
Unfolded protein response in adipose tissue of obese diabetic women significantly improved 6 months post bariatric surgery, irrespective of malabsorptive or bypass operation type and correlates with plasma glucose concentration
Voyias, P, Antonysunil, A, Kumasaiyai, W, Kyrou, I, Vrbikova, J, Hainer, V, Fried, M, Sramkova, P, Saravanan, P, Kumar, S, McTernan, P and Tripathi, G 2014. Unfolded protein response in adipose tissue of obese diabetic women significantly improved 6 months post bariatric surgery, irrespective of malabsorptive or bypass operation type and correlates with plasma glucose concentration. bioscientifica. https://doi.org/10.1530/endoabs.34.P269
A 3-month low fat diet leads to significant lipid profile improvement in obese T2DM Saudi subjects, without substantial weight loss, and the capacity to manage a damaging high-fat meal challenge more appropriately post intervention
Al-Disi, D, Al-Daghri, N, Khan, N, Alsaif, M, Alfadda, A, Sabico, S, Tripathi, G and McTernan, P 2014. A 3-month low fat diet leads to significant lipid profile improvement in obese T2DM Saudi subjects, without substantial weight loss, and the capacity to manage a damaging high-fat meal challenge more appropriately post intervention. bioscientifica. https://doi.org/10.1530/endoabs.34.P223
Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro
Pushpakom, S.P, Adaikalakoteswari, A, Owen, A, Back, D.J, Tripathi, G, Kumar, S, McTernan, P and Pirmohamed, M 2018. Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. Diabetes and Vascular Disease Research. https://doi.org/10.1177/1479164118757924
Vitamin D receptor gene polymorphisms modify cardiometabolic response to vitamin D supplementation in T2DM patients
Al-Daghri, N.M, Mohammed, A.K, Al-Attas, O.S, Ansari, M.G.A, Wani, K, Hussain, S.D, Sabico, S, Tripathi, G and Alokail, M.S 2017. Vitamin D receptor gene polymorphisms modify cardiometabolic response to vitamin D supplementation in T2DM patients. Scientific Reports. https://doi.org/10.1038/s41598-017-08621-7
Recepteur d'Origine nantais (RON) tyrosine kinase splicing variants lacking exons 18 and 19 occur ubiquitously in lung cancer
Krishnaswamy, S, Mohammed, A.K, Amer, O.E, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2015. Recepteur d'Origine nantais (RON) tyrosine kinase splicing variants lacking exons 18 and 19 occur ubiquitously in lung cancer. International Journal of Clinical and Experimental Medicine.
Elevated cord leptin from low B12 mothers predicts birth weight
Antonysunil, A, Vatish, M, Lawson, A, Wood, C, Sivakumar, K, Webster, C, Anderson, N, McTernan, P, Tripathi, G and Saravanan, P 2014. Elevated cord leptin from low B12 mothers predicts birth weight. bioscientifica. https://doi.org/10.1530/endoabs.34.P262
PWE-254 Is the macroscopically normal mucosa (MNM) around colorectal cancer really ‘normal’?
Patel, A, Fang, Y, Moore, J, Williams, N, Tripathi, G and Arasaradnam, R 2015. PWE-254 Is the macroscopically normal mucosa (MNM) around colorectal cancer really ‘normal’? Gut. https://doi.org/10.1136/gutjnl-2015-309861.700
Meal size and frequency influences metabolic endotoxaemia and inflammatory risk but has no effect on diet induced thermogenesis in either lean or obese subjects
Piya, M, Reddy, N, Campbell, A, Hattersley, J, Halder, L, Tripathi, G, Tahrani, A, Kumar, S, Barber, T and McTernan, P 2014. Meal size and frequency influences metabolic endotoxaemia and inflammatory risk but has no effect on diet induced thermogenesis in either lean or obese subjects. bioscientifica. https://doi.org/10.1530/endoabs.34.P226
Splice variants of the extracellular region of RON receptor tyrosine kinase in lung cancer cell lines identified by PCR and sequencing
Krishnaswamy, S, Mohammed, A.K, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2017. Splice variants of the extracellular region of RON receptor tyrosine kinase in lung cancer cell lines identified by PCR and sequencing. BMC Cancer. https://doi.org/10.1186/s12885-017-3747-x
Identification of the splice variants of Recepteur d'Origine nantais (RON) in lung cancer cell lines
Krishnaswamy, S, Bukhari, I, Mohammed, A.K, Amer, O.E, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2018. Identification of the splice variants of Recepteur d'Origine nantais (RON) in lung cancer cell lines. Gene. https://doi.org/10.1016/j.gene.2018.09.027
Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2
Al‐Daghri, N.M, Alokail, M.S, Rahman, S, Amer, O.E, Al‐Attas, O.S, Alfawaz, H, Tripathi, G, Sabico, S., Chrousos, G.P, McTernan, P.G and Piya, M.K 2015. Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2. European Journal of Clinical Investigation. https://doi.org/10.1111/eci.12468
Novel splicing variants of recepteur d'origine nantais (RON) tyrosine kinase involving exons 15–19 in lung cancer
Krishnaswamy, S, Mohammed, A.K, Amer, O.E, Tripathi, G, Alokail, M.S and Al-Daghri, N.M 2015. Novel splicing variants of recepteur d'origine nantais (RON) tyrosine kinase involving exons 15–19 in lung cancer. Lung Cancer. https://doi.org/10.1016/j.lungcan.2015.12.002
Field cancerisation in colorectal cancer: A new frontier or pastures past?
Patel, A, Tripathi, G, Gopalakrishnan, K, Williams, N and Arasaradnam, R.P 2015. Field cancerisation in colorectal cancer: A new frontier or pastures past? World Journal of Gastroenterology. https://doi.org/10.3748/wjg.v21.i13.3763
Freeze dried broccoli extract relieves ER stress and mitochondrial inefficiency in differentiated human pre-adipocyte cells
Murphy, A, Jackisch, L., Azharian, S, Aladel, A, Barker, G, Tripathi, G, Chappell, M and McTernan, P 2014. Freeze dried broccoli extract relieves ER stress and mitochondrial inefficiency in differentiated human pre-adipocyte cells. bioscientifica. https://doi.org/10.1530/endoabs.44.P191
Systemic triglycerides as a key determinant of TLR regulated inflammatory risk in human adipose tissue post bariatric surgical intervention and weight loss
Kumsaiyai, W, Al-Daghri, N, Kyrou, I, Vrbikova, J, Hainer, V, Fried, M, Sramkova, P, Barber, T, S Kumar, Tripathi, G and McTernan, P 2014. Systemic triglycerides as a key determinant of TLR regulated inflammatory risk in human adipose tissue post bariatric surgical intervention and weight loss. bioscientifica. https://doi.org/10.1530/endoabs.34.P238
Tunicamycin-induced ER stress mediates mitochondrial dysfunction in human adipocytes
Jackisch, L, Murphy, A, Al-Daghri, N, McTernan, P, Randeva, H and Tripathi, G 2014. Tunicamycin-induced ER stress mediates mitochondrial dysfunction in human adipocytes. bioscientifica. https://doi.org/10.1530/endoabs.44.P193
Methyl donor deficiency due to low vitamin b12 impairs insulin signalling in human adipocytes by down regulating AKT pathway via PTEN and TRB3
Adaikalakoteswari, A, Finer, S, Voyias, P.D, McCarthy, M, Vatish, M, Moore, J, Smart-Halajko, M, Bawazeer, N, Al-Daghri, N.M, McTernan, P.G, Hitman, G.A, Saravanan, P and Tripathi, G 2014. Methyl donor deficiency due to low vitamin b12 impairs insulin signalling in human adipocytes by down regulating AKT pathway via PTEN and TRB3. American Diabetes Association.
Vitamin B12 deficiency induces adipocyte dysfunction via enhanced cholesterol biosynthesis, unfolded protein response and associated epigenetic marks
Finer, S, Hitman, G.A, Saravanan, P and Tripathi, G 2014. Vitamin B12 deficiency induces adipocyte dysfunction via enhanced cholesterol biosynthesis, unfolded protein response and associated epigenetic marks. Norwich Research ParK.
The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes
Piya, Milan K, Harte, A. L, Sivakumar, K, Tripathi, G, Voyias, P. D, James, S, Sabico, S, Al-Daghri, N, M, Saravanan, P, Barber, T. M, Kumar, S, Vatish, M and McTernan, P. G 2014. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. American Journal of Physiology Endocrinology and Metabolism. https://doi.org/10.1152/ajpendo.00308.2013
Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes.
Adaikalakoteswari, A, Jayashri, R, Sukumar, N, Venkataraman, H, Pradeepa, R, Gokulakrishnan, K, Anjana, R.M, McTernan, P.G, Tripathi, G, Patel, V and Kumar, S. 2014. Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes. Cardiovascular Diabetology. https://doi.org/10.1186/s12933-014-0129-4
Low maternal vitamin B12 status is associated with lower cord blood HDL cholesterol in white caucasians living in the UK
Adaikalakoteswari, A, Vatish, M, Lawson, A, Wood, C, Sivakumar, K, McTernan, P, Webster, C, Anderson, N, Yajnik, C, Tripathi, G and Saravanan, P 2015. Low maternal vitamin B12 status is associated with lower cord blood HDL cholesterol in white caucasians living in the UK. Nutrients. https://doi.org/10.3390/nu7042401
Enhanced thermic effect of food, postprandial NEFA suppression and raised adiponectin in obese women who eat slowly.
Reddy, N.L, Peng, C, Carreira, M.C, Halder, L, Hattersley, J, Piya, M.K, Tripathi, G, Randeva, H.S, Casanueva, F.F, McTernan, P.G and Kumar, S 2014. Enhanced thermic effect of food, postprandial NEFA suppression and raised adiponectin in obese women who eat slowly. Cinical Endocrinology. https://doi.org/10.1111/cen.12652
Maternal inheritance of circulating irisin in humans.
Al-Daghri, N.M, Al-Attas, O.S, Alokail, M.S, Alkharfy, K.M, Yousef, M, Vinodson, B, Amer, O.E, Alnaami, A.M, Sabico, S, Tripathi, G and Piya, M.K. 2014. Maternal inheritance of circulating irisin in humans. Clincal Science. https://doi.org/10.1042/CS20130426
Surface charge visualization at viable living cells
Perry, D, Paulose Nadappuram, B, Momotenko, D, Voyias, P.D, Page, A, Tripathi, G, Frenguelli, B.G and Unwin, P.R 2016. Surface charge visualization at viable living cells. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.5b13153
Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery.
de la Escalera, L.M, Kyrou, I, Vrbikova, J, Hainer, V, Sramkova, P, Fried, M, Piya, M.K, Kumar, S, Tripathi, G and McTernan, P.G 2017. Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery. BMC Medicine. https://doi.org/10.1186/s12916-017-0797-5
Identification of brown adipose tissue using MR imaging in a human adult with histological and immunohistochemical confirmation.
Reddy, N.L, Jones, T.A, Wayte, S.C, Adesanya, O, Sankar, S, Yeo, Y.C, Tripathi, G, McTernan, P.G, Randeva, H.S, Kumar, S and Hutchinson, C.E 2014. Identification of brown adipose tissue using MR imaging in a human adult with histological and immunohistochemical confirmation. The Journal of clinical endocrinology and metabolism. https://doi.org/10.1210/jc.2013-2036
Postprandial effect of a high-fat meal on endotoxemia in Arab women with and without insulin-resistance-related diseases.
Al-Disi, D, A-Daghri, N, Khan, N, Alfadda, A, Sallam, R, Alsaif, M, Sabico, S, Tripathi, G and McTernan, P 2015. Postprandial effect of a high-fat meal on endotoxemia in Arab women with and without insulin-resistance-related diseases. Nutrients. https://doi.org/10.3390/nu7085290
Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes.
Hu, J, Kyrou, I, Tan, B.K, Dimitriadis, G.K, Ramanjaneya, M, Tripathi, G, Patel, V, James, S, Kawan, M, Chen, J and Randeva, H.S 2016. Short-chain fatty acid acetate stimulates adipogenesis and mitochondrial biogenesis via GPR43 in brown adipocytes. Endocrinology. https://doi.org/10.1210/en.2015-1944
Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects
Al-Daghri, N.M, Rahman, S, Sabico, S, Yakout, S, Wani, K, Al-Attas, O.S, Saravanan, P, Tripathi, G, McTernan, P.G and Alokail, M.S 2016. Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects. Nutrients. https://doi.org/10.3390/nu8090460