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3. Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses

Author

Bos, Maxime M., Goulding, Neil J., Lee, Matthew A., Hofman, Amy, Bot, Mariska, Pool, René, Vijfhuizen, Lisanne S., Zhang, Xiang, Li, Chihua, Mustafa, Rima, Neville, Matt J., Li-Gao, Ruifang, Trompet, Stella, Beekman, Marian, Biermasz, Nienke R., Boomsma, Dorret I., de Boer, Irene, Christodoulides, Constantinos, Dehghan, Abbas, van Dijk, Ko Willems, Ford, Ian, Ghanbari, Mohsen, Heijmans, Bastiaan T., Ikram, M. Arfan, Jukema, J. Wouter, Mook-Kanamori, Dennis O., Karpe, Fredrik, Luik, Annemarie I., Lumey, L. H., van den Maagdenberg, Arn M. J. M., Mooijaart, Simon P., de Mutsert, Renée, Penninx, Brenda W. J. H., Rensen, Patrick C. N., Richmond, Rebecca C., Rosendaal, Frits R., Sattar, Naveed, Schoevers, Robert A., Slagboom, P. Eline, Terwindt, Gisela M., Thesing, Carisha S., Wade, Kaitlin H., Wijsman, Carolien A., Willemsen, Gonneke, Zwinderman, Aeilko H., van Heemst, Diana, Noordam, Raymond, and Lawlor, Deborah A.

Published
2021
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4. Evaluation of endocrine complications in beta-thalassemia intermedia (β-TI): a cross-sectional multicenter study

Author

Karimi, Mehran, Zarei, Tahereh, Haghpanah, Sezaneh, Azarkeivan, Azita, Kattamis, Christos, Ladis, Vassilis, Kattamis, Antonios, Kilinc, Yurdanur, Daar, Shahina, Alyaarubi, Saif, Khater, Doaa, Wali, Yasser, Elshinawy, Mohamed, Almadhani, Ali, Yassin, Mohamed, Soliman, Ashraf T., Canatan, Duran, Obiedat, Maha, Al-Rimawi, Hala, Mariannis, Demetris, Christodoulides, Constantinos, Christou, Soteroula, Tzoulis, Ploutarchos, Campisi, Saveria, Di Maio, Salvatore, and De Sanctis, Vincenzo

Published
2020
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8. Dact1, a Nutritionally Regulated Preadipocyte Gene, Controls Adipogenesis by Coordinating the Wnt/β-Catenin Signaling Network

Author

Lagathu, Claire, Christodoulides, Constantinos, Virtue, Sam, Cawthorn, William P, Franzin, Chiara, Kimber, Wendy A, Nora, Edoardo Dalla, Campbell, Mark, Medina-Gomez, Gema, Cheyette, Benjamin NR, Vidal-Puig, Antonio J, and Sethi, Jaswinder K

Subjects
Biomedical and Clinical Sciences, Genetics, Nutrition, Obesity, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Cancer, 3T3-L1 Cells, Adaptor Proteins, Signal Transducing, Adipocytes, Adipose Tissue, Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Differentiation, Gene Expression Regulation, Genes, Reporter, Humans, Intracellular Signaling Peptides and Proteins, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, RNA, Messenger, RNA-Binding Proteins, Reverse Transcriptase Polymerase Chain Reaction, TCF Transcription Factors, Transcription Factor 4, Wnt Proteins, beta Catenin, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

ObjectiveWnt signaling inhibits adipogenesis, but its regulation, physiological relevance, and molecular effectors are poorly understood. Here, we identify the Wnt modulator Dapper1/Frodo1 (Dact1) as a new preadipocyte gene involved in the regulation of murine and human adipogenesis.Research design and methodsChanges in Dact1 expression were investigated in three in vitro models of adipogenesis. In vitro gain- and loss-of-function studies were used to investigate the mechanism of Dact1 action during adipogenesis. The in vivo regulation of Dact1 and Wnt/beta-catenin signaling were investigated in murine models of altered nutritional status, of pharmacological stimulation of in vivo adipogenesis, and during the development of dietary and genetic obesity.ResultsDact1 is a preadipocyte gene that decreases during adipogenesis. However, Dact1 knockdown impairs adipogenesis through activation of the Wnt/beta-catenin signaling pathway, and this is reversed by treatment with the secreted Wnt antagonist, secreted Frizzled-related protein 1 (Sfrp1). In contrast, constitutive Dact1 overexpression promotes adipogenesis and confers resistance to Wnt ligand-induced antiadipogenesis through increased expression of endogenous Sfrps and reduced expression of Wnts. In vivo, in white adipose tissue, Dact1 and Wnt/beta-catenin signaling also exhibit coordinated expression profiles in response to altered nutritional status, in response to pharmacological stimulation of in vivo adipogenesis, and during the development of dietary and genetic obesity.ConclusionsDact1 regulates adipogenesis through coordinated effects on gene expression that selectively alter intracellular and paracrine/autocrine components of the Wnt/beta-catenin signaling pathway. These novel insights into the molecular mechanisms controlling adipose tissue plasticity provide a functional network with therapeutic potential against diseases, such as obesity and associated metabolic disorders.

Published
2009

12. HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution

Author

Kuo, Feng-Chih, primary, Neville, Matt J., additional, Sabaratnam, Rugivan, additional, Wesolowska-Andersen, Agata, additional, Phillips, Daniel, additional, Wittemans, Laura B.L., additional, van Dam, Andrea D., additional, Loh, Nellie Y., additional, Todorčević, Marijana, additional, Denton, Nathan, additional, Kentistou, Katherine A., additional, Joshi, Peter K., additional, Christodoulides, Constantinos, additional, Langenberg, Claudia, additional, Collas, Philippe, additional, Karpe, Fredrik, additional, and Pinnick, Katherine E., additional

Published
2022
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14. Apolipoprotein A-V is a potential target for treating coronary artery disease: evidence from genetic and metabolomic analyses

Author

Ibi, Dorina, primary, Boot, Manon, additional, Dollé, Martijn E.T., additional, Jukema, J. Wouter, additional, Rosendaal, Frits R., additional, Christodoulides, Constantinos, additional, Neville, Matt J., additional, Koivula, Robert, additional, Rensen, Patrick C.N., additional, Karpe, Fredrik, additional, Noordam, Raymond, additional, and Willems van Dijk, Ko, additional

Published
2022
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19. Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk:evidence from multi-cohort Mendelian randomization and metabolomic profiling

Author

van Vliet, Nicolien A., Bos, Maxime M., Thesing, Carisha S., Chaker, Layal, Pietzner, Maik, Houtman, Evelyn, Neville, Matt J., Li-Gao, Ruifang, Trompet, Stella, Mustafa, Rima, Ahmadizar, Fariba, Beekman, Marian, Bot, Mariska, Budde, Kathrin, Christodoulides, Constantinos, Dehghan, Abbas, Delles, Christian, Elliott, Paul, Evangelou, Marina, Gao, He, Ghanbari, Mohsen, van Herwaarden, Antonius E., Ikram, M. Arfan, Jaeger, Martin, Jukema, J. Wouter, Karaman, Ibrahim, Karpe, Fredrik, Kloppenburg, Margreet, Meessen, Jennifer M.T.A., Meulenbelt, Ingrid, Milaneschi, Yuri, Mooijaart, Simon P., Mook-Kanamori, Dennis O., Netea, Mihai G., Netea-Maier, Romana T., Peeters, Robin P., Penninx, Brenda W.J.H., Sattar, Naveed, Slagboom, P. Eline, Suchiman, H. Eka D., Völzke, Henry, Willems van Dijk, Ko, Noordam, Raymond, van Heemst, Diana, van Vliet, Nicolien A., Bos, Maxime M., Thesing, Carisha S., Chaker, Layal, Pietzner, Maik, Houtman, Evelyn, Neville, Matt J., Li-Gao, Ruifang, Trompet, Stella, Mustafa, Rima, Ahmadizar, Fariba, Beekman, Marian, Bot, Mariska, Budde, Kathrin, Christodoulides, Constantinos, Dehghan, Abbas, Delles, Christian, Elliott, Paul, Evangelou, Marina, Gao, He, Ghanbari, Mohsen, van Herwaarden, Antonius E., Ikram, M. Arfan, Jaeger, Martin, Jukema, J. Wouter, Karaman, Ibrahim, Karpe, Fredrik, Kloppenburg, Margreet, Meessen, Jennifer M.T.A., Meulenbelt, Ingrid, Milaneschi, Yuri, Mooijaart, Simon P., Mook-Kanamori, Dennis O., Netea, Mihai G., Netea-Maier, Romana T., Peeters, Robin P., Penninx, Brenda W.J.H., Sattar, Naveed, Slagboom, P. Eline, Suchiman, H. Eka D., Völzke, Henry, Willems van Dijk, Ko, Noordam, Raymond, and van Heemst, Diana

Abstract

Background: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. Methods: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. Results: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99–1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96–1.04; p value

Published
2021

21. Associations between outdoor temperature and bright sunlight with metabolites in two population-based European cohorts

Author

Eveleens Maarse, Boukje C., primary, Loh, Nellie Y., additional, Karpe, Fredrik, additional, Rosendaal, Frits R., additional, van Heemst, Diana, additional, Mook-Kanamori, Dennis O., additional, Willems van Dijk, Ko, additional, Rensen, Patrick C.N., additional, Kooijman, Sander, additional, Christodoulides, Constantinos, additional, and Noordam, Raymond, additional

Published
2020
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23. Investigating the relationships between unfavorable sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses

Author

Bos, Maxime M, primary, Goulding, Neil J, additional, Lee, Matthew A, additional, Hofman, Amy, additional, Bot, Mariska, additional, Pool, René, additional, Vijfhuizen, Lisanne S, additional, Zhang, Xiang, additional, Li, Chihua, additional, Mustafa, Rima, additional, Neville, Matt J, additional, Li-Gao, Ruifang, additional, Trompet, Stella, additional, Beekman, Marian, additional, Biermasz, Nienke R, additional, Boomsma, Dorret I, additional, Boer, Irene de, additional, Christodoulides, Constantinos, additional, Dehghan, Abbas, additional, Dijk, Ko Willems van, additional, Ford, Ian, additional, Gao, He, additional, Ghanbari, Mohsen, additional, Heijmans, Bastiaan T, additional, Ikram, M Arfan, additional, Jukema, J Wouter, additional, Mook-Kanamori, Dennis O, additional, Karpe, Fredrik, additional, Luik, Annemarie I, additional, Lumey, L.H., additional, van den Maagdenberg, Arn M.J.M., additional, Mooijaart, Simon P, additional, Mutsert, Renée de, additional, Penninx, Brenda W.J.H., additional, Rensen, Patrick CN, additional, Richmond, Rebecca C, additional, Rosendaal, Frits R, additional, Sattar, Naveed, additional, Schoevers, Robert A, additional, Slagboom, P Eline, additional, Terwindt, Gisela M, additional, Thesing, Carisha S, additional, Wade, Kaitlin H, additional, Wijsman, Carolien A, additional, Willemsen, Gonneke, additional, Zwinderman, Aeilko H., additional, Heemst, Diana van, additional, Noordam, Raymond, additional, and Lawlor, Deborah A, additional

Published
2020
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25. Evaluation of endocrine complications in beta-thalassemia intermedia (β-TI): a cross-sectional multicenter study

Author

Karimi, Mehran, primary, Zarei, Tahereh, additional, Haghpanah, Sezaneh, additional, Azarkeivan, Azita, additional, Kattamis, Christos, additional, Ladis, Vassilis, additional, Kattamis, Antonios, additional, Kilinc, Yurdanur, additional, Daar, Shahina, additional, Alyaarubi, Saif, additional, Khater, Doaa, additional, Wali, Yasser, additional, Elshinawy, Mohamed, additional, Almadhani, Ali, additional, Yassin, Mohamed, additional, Soliman, Ashraf T., additional, Canatan, Duran, additional, Obiedat, Maha, additional, Al-Rimawi, Hala, additional, Mariannis, Demetris, additional, Christodoulides, Constantinos, additional, Christou, Soteroula, additional, Tzoulis, Ploutarchos, additional, Campisi, Saveria, additional, Di Maio, Salvatore, additional, and De Sanctis, Vincenzo, additional

Published
2019
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26. Conditionally immortalized brown preadipocytes can switch between proliferative and differentiated states

Author

Liu, Jia, primary, Kuipers, Eline N., additional, Sips, Hetty C.M., additional, Dorleijn, Jennifa C., additional, van Dam, Andrea D., additional, Christodoulides, Constantinos, additional, Karpe, Fredrik, additional, Zhou, Guangqian, additional, Boon, Mariëtte R., additional, Rensen, Patrick C.N., additional, de Vries, Antoine A.F., additional, and Kooijman, Sander, additional

Published
2019
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29. The associations between body fat distribution and bone mineral density in the Oxford Biobank: a cross sectional study.

Author

Hilton, Catriona, Vasan, Senthil K, Neville, Matt J, Christodoulides, Constantinos, and Karpe, Fredrik

Subjects
BONE density, ADIPOSE tissues, FAT, LEAN body mass, BODY composition, DUAL-energy X-ray absorptiometry
Abstract

Body composition is associated with bone mineral density (BMD), but the precise associations between body fat distribution and BMD remain unclear. The regional adipose tissue depots have different metabolic profiles. We hypothesized that they would have independent associations with BMD. We used data from 4,900 healthy individuals aged 30–50 years old from the Oxford Biobank to analyze associations between regional fat mass, lean mass and total BMD. Total lean mass was strongly positively associated with BMD. An increase in total BMD was observed with increasing mass of all the fat depots, as measured either by anthropometry or DXA, when accounting for lean mass. However, on adjustment for both total fat mass and lean mass, fat depot specific associations emerged. Increased android and visceral adipose tissue mass in men, and increased visceral adipose tissue mass in women, were associated with lower BMD. Fat distribution alters the association between adiposity and BMD. [ABSTRACT FROM AUTHOR]

Published
2022
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30. Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling.

Author

van Vliet, Nicolien A., Bos, Maxime M., Thesing, Carisha S., Chaker, Layal, Pietzner, Maik, Houtman, Evelyn, Neville, Matt J., Li-Gao, Ruifang, Trompet, Stella, Mustafa, Rima, Ahmadizar, Fariba, Beekman, Marian, Bot, Mariska, Budde, Kathrin, Christodoulides, Constantinos, Dehghan, Abbas, Delles, Christian, Elliott, Paul, Evangelou, Marina, and Gao, He

Subjects
THYROID diseases, CARDIOVASCULAR diseases, CARDIOVASCULAR diseases risk factors, CORONARY artery disease, METABOLOMICS, THYROTROPIN, LIPIDS
Abstract

Background: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status.Methods: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction.Results: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59).Conclusions: Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Published
2021
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32. Adipose tissue-derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases

Author

Akoumianakis, Ioannis Sanna, Fabio Margaritis, Marios Badi, Ileana Akawi, Nadia Herdman, Laura Coutinho, Patricia and Fagan, Harry Antonopoulos, Alexios S. Oikonomou, Evangelos K. and Thomas, Sheena Chiu, Amy P. Chuaiphichai, Surawee and Kotanidis, Christos P. Christodoulides, Constantinos Petrou, Mario Krasopoulos, George Sayeed, Rana Lv, Lei Hale, Ashley Kararoudi, Meisam Naeimi McNeill, Eileen Douglas, Gillian George, Sarah Tousoulis, Dimitris Channon, Keith M. and Antoniades, Charalambos

Subjects
embryonic structures, sense organs
Abstract

Obesity is associated with changes in the secretome of adipose tissue (AT), which affects the vasculature through endocrine and paracrine mechanisms. Wingless-related integration site 5A (WNT5A) and secreted frizzled-related protein 5 (SFRP5), adipokines that regulate noncanonical Wnt signaling, are dysregulated in obesity. We hypothesized that WNT5A released from AT exerts endocrine and paracrine effects on the arterial wall through noncanonical RAC1-mediated Wnt signaling. In a cohort of 1004 humans with atherosclerosis, obesity was associated with increased WNT5A bioavailability in the circulation and the AT, higher expression of WNT5A receptors Frizzled 2 and Frizzled 5 in the human arterial wall, and increased vascular oxidative stress due to activation of NADPH oxidases. Plasma concentration of WNT5A was elevated in patients with coronary artery disease compared to matched controls and was independently associated with calcified coronary plaque progression. We further demonstrated that WNT5A induces arterial oxidative stress and redox-sensitive migration of vascular smooth muscle cells via Frizzled 2-mediated activation of a previously uncharacterized pathway involving the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) and the GTPase RAC1. Our study identifies WNT5A and its downstream vascular signaling as a link between obesity and vascular disease pathogenesis, with translational implications in humans.

Published
2019

33. The Link Between Nutritional Status and Insulin Sensitivity Is Dependent on the Adipocyte-Specific Peroxisome Proliferator–Activated Receptor-γ2 Isoform

Author

Medina-Gomez, Gema, Virtue, Sam, Lelliott, Christopher, Boiani, Romina, Campbell, Mark, Christodoulides, Constantinos, Perrin, Christophe, Jimenez-Linan, Mercedes, Blount, Margaret, Dixon, John, Zahn, Dirk, Thresher, Rosemary R., Aparicio, Sam, Carlton, Mark, Colledge, William H., Kettunen, Mikko I., Seppänen-Laakso, Tuulikki, Sethi, Jaswinder K., OʼRahilly, Stephen, Brindle, Kevin, Cinti, Saverio, Oresic, Matej, Burcelin, Remy, and Vidal-Puig, Antonio

Published
2005

35. The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator--activated receptor-[gamma]2 isoform

Author

Medina-Gomez, Gema, Virtue, Sam, Lelliott, Christopher, Boiani, Romina, Campbell, Mark, Christodoulides, Constantinos, Perrin, Christophe, Jimenez-Linan, Mercedes, Blount, Margaret, Dixon, John, Zahn, Dirk, Thresher, Rosemary R., Aparicio, Sam, Carlton, Mark, Colledge, William H., Kettunen, Mikko I., Seppanen-Laakso, Tuulikki, Sethi, Jaswinder K., O'Rahilly, Stephen, Brindle, Kevin, Cinti, Saverio, Oresic, Matej, Burcelin, Remy, and Vidal-Puig, Antonio

Subjects
Obesity -- Research, Peroxisomes, Insulin, Fat cells, Health
Abstract

The nuclear receptor peroxisome proliferator-activated receptor-[gamma] (PPAR[gamma]) is critically required for adipogenesis. PPAR[gamma] exists as two isoforms, [gamma]1 and [gamma]2. PPAR[gamma]2 is the more potent adipogenic isoform in vitro and is normally restricted to adipose tissues, where it is regulated more by nutritional state than PPAR[gamma]1. To elucidate the relevance of the PPAR[gamma]2 in vivo, we generated a mouse model in which the PPAR[gamma]2 isoform was specifically disrupted. Despite similar weight, body composition, food intake, energy expenditure, and adipose tissue morphology, male mice lacking the [gamma]2 isoform were more insulin resistant than wild-type animals when fed a regular diet. These results indicate that insulin resistance associated with ablation of PPAR[gamma]2 is not the result of lipodystrophy and suggests a specific role for PPAR[gamma]2 in maintaining insulin sensitivity independently of its effects on adipogenesis. Furthermore, PPAR[gamma]2 knockout mice fed a high-fat diet did not become more insulin resistant than those on a normal diet, despite a marked increase in their mean adipocyte cell size. These findings suggest that PPAR[gamma]2 is required for the maintenance of normal insulin sensitivity in mice but also raises the intriguing notion that PPAR[gamma]2 may be necessary for the adverse effects of a high-fat diet on carbohydrate metabolism., Peroxisome proliferator-activated receptor-[gamma] (PPAR[gamma]) plays a central role in adipogenesis and insulin sensitivity. PPAR[gamma] is expressed as two isoforms, PPAR[gamma]1 and PPAR[gamma]2, which differ only in that PPAR[gamma]2 has 30 [...]

Published
2005

36. Evaluation of Endocrine Complications in Beta-Thalassemia Intermedia Patients: A Cross Sectional Multi-Center Study

Author

Karimi, Mehran Zarei, Tahereh Haghpanah, Sezaneh Azarkeivan, Azita Kattamis, Christos Ladis, Vassilis Kilinc, Yurdanur and Daar, Shahina Alyaarubi, Saif Yasseen, Duaa Yassin, Mohamed A. Soliman, Ashraf Tawfiq Canatan, Duran Obiedat, Maha Remawi, Hala Mariannis, Demetris Christodoulides, Constantinos Christou, Soteroula Tzoulis, Ploutarchos De Sanctis, Vincenzo

Published
2018

37. Associations between outdoor temperature and bright sunlight with metabolites in two population-based European cohorts

Author

Eveleens Maarse, Boukje C, primary, Loh, Nellie Y., additional, Karpe, Fredrik, additional, Rosendaal, Frits R, additional, van Heemst, Diana, additional, Mook-Kanamori, Dennis O, additional, van Dijk, Ko Willems, additional, Rensen, Patrick CN, additional, Kooijman, Sander, additional, Christodoulides, Constantinos, additional, and Noordam, Raymond, additional

Published
2019
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38. Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases

Author

Akoumianakis, Ioannis, primary, Sanna, Fabio, additional, Margaritis, Marios, additional, Badi, Ileana, additional, Akawi, Nadia, additional, Herdman, Laura, additional, Coutinho, Patricia, additional, Fagan, Harry, additional, Antonopoulos, Alexios S., additional, Oikonomou, Evangelos K., additional, Thomas, Sheena, additional, Chiu, Amy P., additional, Chuaiphichai, Surawee, additional, Kotanidis, Christos P., additional, Christodoulides, Constantinos, additional, Petrou, Mario, additional, Krasopoulos, George, additional, Sayeed, Rana, additional, Lv, Lei, additional, Hale, Ashley, additional, Naeimi Kararoudi, Meisam, additional, McNeill, Eileen, additional, Douglas, Gillian, additional, George, Sarah, additional, Tousoulis, Dimitris, additional, Channon, Keith M., additional, and Antoniades, Charalambos, additional

Published
2019
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41. Evaluation of Endocrine Complications in Beta-Thalassemia Intermedia Patients: A Cross Sectional Multi-Center Study

Author

Karimi, Mehran, primary, Zarei, Tahereh, additional, Haghpanah, Sezaneh, additional, Azarkeivan, Azita, additional, Kattamis, Christos, additional, Ladis, Vassilis, additional, Kilinc, Yurdanur, additional, Daar, Shahina, additional, Alyaarubi, Saif, additional, Yasseen, Duaa, additional, Yassin, Mohamed A, additional, Soliman, Ashraf Tawfiq, additional, Canatan, Duran, additional, Obiedat, Maha, additional, Remawi, Hala, additional, Mariannis, Demetris, additional, Christodoulides, Constantinos, additional, Christou, Soteroula, additional, Tzoulis, Ploutarchos, additional, and De Sanctis, Vincenzo, additional

Published
2018
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42. A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening

Author

van den Berg, Rosa, Kooijman, Sander, Noordam, Raymond, Ramkisoensing, Ashna, Abreu-Vieira, Gustavo, Tambyrajah, Lauren L., Dijk, Wieneke, Ruppert, Philip, Mol, Isabel M., Kramar, Barbara, Caputo, Rosanna, Puig, Laura Sardón, de Ruiter, Evelien M., Kroon, Jan, Hoekstra, Menno, van der Sluis, Ronald J., Meijer, Onno C., Willems van Dijk, Ko, van Kerkhof, Linda W.M., Christodoulides, Constantinos, Karpe, Fredrik, Gerhart-Hines, Zachary, Kersten, Sander, Meijer, Johanna H., Coomans, Claudia P., van Heemst, Diana, Biermasz, Nienke R., Rensen, Patrick C.N., van den Berg, Rosa, Kooijman, Sander, Noordam, Raymond, Ramkisoensing, Ashna, Abreu-Vieira, Gustavo, Tambyrajah, Lauren L., Dijk, Wieneke, Ruppert, Philip, Mol, Isabel M., Kramar, Barbara, Caputo, Rosanna, Puig, Laura Sardón, de Ruiter, Evelien M., Kroon, Jan, Hoekstra, Menno, van der Sluis, Ronald J., Meijer, Onno C., Willems van Dijk, Ko, van Kerkhof, Linda W.M., Christodoulides, Constantinos, Karpe, Fredrik, Gerhart-Hines, Zachary, Kersten, Sander, Meijer, Johanna H., Coomans, Claudia P., van Heemst, Diana, Biermasz, Nienke R., and Rensen, Patrick C.N.

Abstract

Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism. We observed a high-amplitude rhythm in fatty acid uptake by BAT that synchronized with the light/dark cycle. Highest uptake was found at the onset of the active period, which coincided with high lipoprotein lipase expression and low angiopoietin-like 4 expression by BAT. Diurnal rhythmicity in BAT activity determined the rate at which lipids were cleared from the circulation, thereby imposing the daily rhythm in plasma lipid concentrations. In mice as well as humans, postprandial lipid excursions were nearly absent at waking. We anticipate that diurnal BAT activity is an important factor to consider when studying the therapeutic potential of promoting BAT activity. van den Berg et al. show a strong circadian rhythm in fatty acid uptake by brown adipose tissue that peaks at wakening regardless of the light exposure period. Consequently, postprandial lipid handling by brown adipose tissue is highest at wakening, resulting in the lowest postprandial plasma lipid excursions.

Published
2018

43. A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening

Author

van den Berg, Rosa, primary, Kooijman, Sander, additional, Noordam, Raymond, additional, Ramkisoensing, Ashna, additional, Abreu-Vieira, Gustavo, additional, Tambyrajah, Lauren L., additional, Dijk, Wieneke, additional, Ruppert, Philip, additional, Mol, Isabel M., additional, Kramar, Barbara, additional, Caputo, Rosanna, additional, Puig, Laura Sardón, additional, de Ruiter, Evelien M., additional, Kroon, Jan, additional, Hoekstra, Menno, additional, van der Sluis, Ronald J., additional, Meijer, Onno C., additional, Willems van Dijk, Ko, additional, van Kerkhof, Linda W.M., additional, Christodoulides, Constantinos, additional, Karpe, Fredrik, additional, Gerhart-Hines, Zachary, additional, Kersten, Sander, additional, Meijer, Johanna H., additional, Coomans, Claudia P., additional, van Heemst, Diana, additional, Biermasz, Nienke R., additional, and Rensen, Patrick C.N., additional

Published
2018
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45. LRP5 Regulates Human Body Fat Distribution by Modulating Adipose Progenitor Biology in a Dose- and Depot-Specific Fashion

Author

Loh, Nellie Y. Neville, Matt J. Marinou, Kyriakoula and Hardcastle, Sarah A. Fielding, Barbara A. Duncan, Emma L. and McCarthy, Mark I. Tobias, Jonathan H. Gregson, Celia L. and Karpe, Fredrik Christodoulides, Constantinos

Abstract

Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired beta-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/beta-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders.

Published
2015

50. ETO/MTG8 Is an Inhibitor of C/EBPβ Activity and a Regulator of Early Adipogenesis

Author

Rochford, Justin J., primary, Semple, Robert K., additional, Laudes, Matthias, additional, Boyle, Keith B., additional, Christodoulides, Constantinos, additional, Mulligan, Claire, additional, Lelliott, Christopher J., additional, Schinner, Sven, additional, Hadaschik, Dirk, additional, Mahadevan, Meera, additional, Sethi, Jaswinder K., additional, Vidal-Puig, Antonio, additional, and O'Rahilly, Stephen, additional

Published
2004
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