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1. Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use

Author

Worthmann, Anna, Ridder, Julius, Piel, Sharlaine Y. L., Evangelakos, Ioannis, Musfeldt, Melina, Voß, Hannah, O’Farrell, Marie, Fischer, Alexander W., Adak, Sangeeta, Sundd, Monica, Siffeti, Hasibullah, Haumann, Friederike, Kloth, Katja, Bierhals, Tatjana, Heine, Markus, Pertzborn, Paul, Pauly, Mira, Scholz, Julia-Josefine, Kundu, Suman, Fuh, Marceline M., Neu, Axel, Tödter, Klaus, Hempel, Maja, Knippschild, Uwe, Semenkovich, Clay F., Schlüter, Hartmut, Heeren, Joerg, Scheja, Ludger, Kubisch, Christian, and Schlein, Christian

Published
2024
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2. Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use

Author

Worthmann, Anna, primary, Ridder, Julius, additional, Piel, Sharlaine, additional, Evangelakos, Ioannis, additional, Musfeldt, Melina, additional, Voß, Hannah, additional, O'Farell, Marie, additional, Fischer, Alexander, additional, Adak, Sangeeta, additional, Sundd, Monica, additional, Siffeti, Hasibullah, additional, Haumann, Friederike, additional, Kloth, Katja, additional, Bierhals, Tatjana, additional, Heine, Markus, additional, Pertzborn, Paul, additional, Pauly, Mira, additional, Scholz, Julia-Josefine, additional, Kundu, Suman, additional, Fuh, Manka, additional, Neu, Axel, additional, Tödter, Klaus, additional, Hempel, Maja, additional, Knippschild, Uwe, additional, Semenkovich, Clay, additional, Schlüter, Hartmut, additional, Heeren, Joerg, additional, Scheja, Ludger, additional, Kubisch, Christian, additional, and Schlein, Christian, additional

Published
2023
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7. Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use

Author

Schlein, Christian, primary, Worthmann, Anna, additional, Piel, Sharlaine, additional, Fischer, Alexander, additional, O'Farell, Marie, additional, Adak, Sangeeta, additional, Kloth, Katja, additional, Sundd, Monica, additional, Siffeti, Hasibullah, additional, Musfeldt, Melina, additional, Bierhals, Tatjana, additional, Heine, Markus, additional, Pauly, Mira, additional, Haumann, Friederike, additional, Kundu, Suman, additional, Fuh, Manka, additional, Neu, Axel, additional, Beysen, Carine, additional, Pertzborn, Paul, additional, Schlüter, Hartmut, additional, Knippschild, Uwe, additional, Tödter, Klaus, additional, Hempel, Maja, additional, Semenkovich, Clay, additional, Heeren, Joerg, additional, Scheja, Ludger, additional, and Kubisch, Christian, additional

Published
2022
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8. Fat quantification in dual-layer detector spectral computed tomography : experimental development and first in-patient validation

Author

Molwitz, Isabel, Campbell, Graeme Michael, Yamamura, Jin, Knopp, Tobias, Tödter, Klaus, Fischer, Roland F., Wang, Zhiyue Jerry, Busch, Alina, Ozga, Ann-Kathrin, Zhang, Shuo, Lindner, Thomas, Sevecke, Florian, Grosser, Mirco, Adam, Gerhard, Szwargulski, Patryk, Molwitz, Isabel, Campbell, Graeme Michael, Yamamura, Jin, Knopp, Tobias, Tödter, Klaus, Fischer, Roland F., Wang, Zhiyue Jerry, Busch, Alina, Ozga, Ann-Kathrin, Zhang, Shuo, Lindner, Thomas, Sevecke, Florian, Grosser, Mirco, Adam, Gerhard, and Szwargulski, Patryk

Abstract

Objectives Fat quantification by dual-energy computed tomography (DECT) provides contrast-independent objective results, for example, on hepatic steatosis or muscle quality as parameters of prognostic relevance. To date, fat quantification has only been developed and used for source-based DECT techniques as fast kVp-switching CT or dual-source CT, which require a prospective selection of the dual-energy imaging mode. It was the purpose of this study to develop a material decomposition algorithm for fat quantification in phantoms and validate it in vivo for patient liver and skeletal muscle using a dual-layer detector-based spectral CT (dlsCT), which automatically generates spectral information with every scan. Materials and Methods For this feasibility study, phantoms were created with 0%, 5%, 10%, 25%, and 40% fat and 0, 4.9, and 7.0 mg/mL iodine, respectively. Phantom scans were performed with the IQon spectral CT (Philips, the Netherlands) at 120 kV and 140 kV and 3 T magnetic resonance (MR) (Philips, the Netherlands) chemical-shift relaxometry (MRR) and MR spectroscopy (MRS). Based on maps of the photoelectric effect and Compton scattering, 3-material decomposition was done for fat, iodine, and phantom material in the image space. After written consent, 10 patients (mean age, 55 ± 18 years; 6 men) in need of a CT staging were prospectively included. All patients received contrast-enhanced abdominal dlsCT scans at 120 kV and MR imaging scans for MRR. As reference tissue for the liver and the skeletal muscle, retrospectively available non-contrast-enhanced spectral CT data sets were used. Agreement between dlsCT and MR was evaluated for the phantoms, 3 hepatic and 2 muscular regions of interest per patient by intraclass correlation coefficients (ICCs) and Bland-Altman analyses. Results The ICC was excellent in the phantoms for both 120 kV and 140 kV (dlsCT vs MRR 0.98 [95% confidence interval (CI), 0.94-0.99]; dlsCT vs MRS 0.96 [95% CI, 0.87-0.99]) and in the skel

Published
2022

11. Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution

Author

Schlein, Christian, Fischer, Alexander W., Sass, Frederike, Worthmann, Anna, Tödter, Klaus, Jaeckstein, Michelle Y., Behrens, Janina, Lynes, Matthew D., Kiebish, Michael A., Narain, Niven R., Bussberg, Val, Darkwah, Abena, Jespersen, Naja Zenius, Nielsen, Søren, Scheele, Camilla, Schweizer, Michaela, Braren, Ingke, Bartelt, Alexander, Tseng, Yu Hua, Heeren, Joerg, Scheja, Ludger, Schlein, Christian, Fischer, Alexander W., Sass, Frederike, Worthmann, Anna, Tödter, Klaus, Jaeckstein, Michelle Y., Behrens, Janina, Lynes, Matthew D., Kiebish, Michael A., Narain, Niven R., Bussberg, Val, Darkwah, Abena, Jespersen, Naja Zenius, Nielsen, Søren, Scheele, Camilla, Schweizer, Michaela, Braren, Ingke, Bartelt, Alexander, Tseng, Yu Hua, Heeren, Joerg, and Scheja, Ludger

Abstract

Thermoneutral conditions typical for standard human living environments result in brown adipose tissue (BAT) involution, characterized by decreased mitochondrial mass and increased lipid deposition. Low BAT activity is associated with poor metabolic health, and BAT reactivation may confer therapeutic potential. However, the molecular drivers of this BAT adaptive process in response to thermoneutrality remain enigmatic. Using metabolic and lipidomic approaches, we show that endogenous fatty acid synthesis, regulated by carbohydrate-response element-binding protein (ChREBP), is the central regulator of BAT involution. By transcriptional control of lipogenesis-related enzymes, ChREBP determines the abundance and composition of both storage and membrane lipids known to regulate organelle turnover and function. Notably, ChREBP deficiency and pharmacological inhibition of lipogenesis during thermoneutral adaptation preserved mitochondrial mass and thermogenic capacity of BAT independently of mitochondrial biogenesis. In conclusion, we establish lipogenesis as a potential therapeutic target to prevent loss of BAT thermogenic capacity as seen in adult humans.

Published
2021

12. Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution

Author

Schlein, Christian, primary, Fischer, Alexander W., additional, Sass, Frederike, additional, Worthmann, Anna, additional, Tödter, Klaus, additional, Jaeckstein, Michelle Y., additional, Behrens, Janina, additional, Lynes, Matthew D., additional, Kiebish, Michael A., additional, Narain, Niven R., additional, Bussberg, Val, additional, Darkwah, Abena, additional, Jespersen, Naja Zenius, additional, Nielsen, Søren, additional, Scheele, Camilla, additional, Schweizer, Michaela, additional, Braren, Ingke, additional, Bartelt, Alexander, additional, Tseng, Yu-Hua, additional, Heeren, Joerg, additional, and Scheja, Ludger, additional

Published
2021
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16. Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain

Author

Scherer, Thomas, primary, Lindtner, Claudia, additional, O’Hare, James, additional, Hackl, Martina, additional, Zielinski, Elizabeth, additional, Freudenthaler, Angelika, additional, Baumgartner-Parzer, Sabina, additional, Tödter, Klaus, additional, Heeren, Joerg, additional, Krššák, Martin, additional, Scheja, Ludger, additional, Fürnsinn, Clemens, additional, and Buettner, Christoph, additional

Published
2016
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18. De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health

Author

Eissing, Leah, primary, Scherer, Thomas, additional, Tödter, Klaus, additional, Knippschild, Uwe, additional, Greve, Jan Willem, additional, Buurman, Wim A., additional, Pinnschmidt, Hans O., additional, Rensen, Sander S., additional, Wolf, Anna M., additional, Bartelt, Alexander, additional, Heeren, Joerg, additional, Buettner, Christoph, additional, and Scheja, Ludger, additional

Published
2013
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20. Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport

Author

Bartelt, Alexander, John, Clara, Schaltenberg, Nicola, Berbée, Jimmy F. P., Worthmann, Anna, Cherradi, M. Lisa, Schlein, Christian, Piepenburg, Julia, Boon, Mariëtte R., Rinninger, Franz, Heine, Markus, Toedter, Klaus, Niemeier, Andreas, Nilsson, Stefan K., Fischer, Markus, Wijers, Sander L., van Marken Lichtenbelt, Wouter, Scheja, Ludger, Rensen, Patrick C. N., and Heeren, Joerg

Abstract

Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. Our findings corroborate the notion that high metabolic activity of thermogenic adipocytes confers atheroprotective properties via increased systemic cholesterol flux through the HDL compartment.

Published
2017
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24. Fat quantification in dual-layer detector spectral computed tomography : experimental development and first in-patient validation

Author

Molwitz, Isabel, Campbell, Graeme Michael, Yamamura, Jin, Knopp, Tobias, Tödter, Klaus, Fischer, Roland F., Wang, Zhiyue Jerry, Busch, Alina, Ozga, Ann-Kathrin, Zhang, Shuo, Lindner, Thomas, Sevecke, Florian, Grosser, Mirco, Adam, Gerhard, and Szwargulski, Patryk

Subjects
sarcopenia, detector-based dual-energy CT, Medizin [610], hepatic steatosis, myosteatosis, material decomposition, spectral CT, dual-layer CT, phantom study, ddc:610, muscle quality, liver
Abstract

Objectives Fat quantification by dual-energy computed tomography (DECT) provides contrast-independent objective results, for example, on hepatic steatosis or muscle quality as parameters of prognostic relevance. To date, fat quantification has only been developed and used for source-based DECT techniques as fast kVp-switching CT or dual-source CT, which require a prospective selection of the dual-energy imaging mode. It was the purpose of this study to develop a material decomposition algorithm for fat quantification in phantoms and validate it in vivo for patient liver and skeletal muscle using a dual-layer detector-based spectral CT (dlsCT), which automatically generates spectral information with every scan. Materials and Methods For this feasibility study, phantoms were created with 0%, 5%, 10%, 25%, and 40% fat and 0, 4.9, and 7.0 mg/mL iodine, respectively. Phantom scans were performed with the IQon spectral CT (Philips, the Netherlands) at 120 kV and 140 kV and 3 T magnetic resonance (MR) (Philips, the Netherlands) chemical-shift relaxometry (MRR) and MR spectroscopy (MRS). Based on maps of the photoelectric effect and Compton scattering, 3-material decomposition was done for fat, iodine, and phantom material in the image space. After written consent, 10 patients (mean age, 55 ± 18 years; 6 men) in need of a CT staging were prospectively included. All patients received contrast-enhanced abdominal dlsCT scans at 120 kV and MR imaging scans for MRR. As reference tissue for the liver and the skeletal muscle, retrospectively available non-contrast-enhanced spectral CT data sets were used. Agreement between dlsCT and MR was evaluated for the phantoms, 3 hepatic and 2 muscular regions of interest per patient by intraclass correlation coefficients (ICCs) and Bland-Altman analyses. Results The ICC was excellent in the phantoms for both 120 kV and 140 kV (dlsCT vs MRR 0.98 [95% confidence interval (CI), 0.94-0.99]; dlsCT vs MRS 0.96 [95% CI, 0.87-0.99]) and in the skeletal muscle (0.96 [95% CI, 0.89-0.98]). For log-transformed liver fat values, the ICC was moderate (0.75 [95% CI, 0.48-0.88]). Bland-Altman analysis yielded a mean difference of -0.7% (95% CI, -4.5 to 3.1) for the liver and of 0.5% (95% CI, -4.3 to 5.3) for the skeletal muscle. Interobserver and intraobserver agreement were excellent (>0.9). Conclusions Fat quantification was developed for dlsCT and agreement with MR techniques demonstrated for patient liver and muscle. Hepatic steatosis and myosteatosis can be detected in dlsCT scans from clinical routine, which retrospectively provide spectral information independent of the imaging mode.

25. De novo lipogenesis in human fat and liver is linked to ChREBP-? and metabolic health.

Author

Eissing, Leah, Scherer, Thomas, Tödter, Klaus, Knippschild, Uwe, Greve, Jan Willem, Buurman, Wim A., Pinnschmidt, Hans O., Rensen, Sander S., Wolf, Anna M., Bartelt, Alexander, Heeren, Joerg, Buettner, Christoph, and Scheja, Ludger

Abstract

Clinical interest in de novo lipogenesis has been sparked by recent studies in rodents demonstrating that de novo lipogenesis specifically in white adipose tissue produces the insulin-sensitizing fatty acid palmitoleate. By contrast, hepatic lipogenesis is thought to contribute to metabolic disease. How de novo lipogenesis in white adipose tissue versus liver is altered in human obesity and insulin resistance is poorly understood. Here we show that lipogenic enzymes and the glucose transporter-4 are markedly decreased in white adipose tissue of insulin-resistant obese individuals compared with non-obese controls. By contrast, lipogenic enzymes are substantially upregulated in the liver of obese subjects. Bariatric weight loss restored de novo lipogenesis and glucose transporter-4 gene expression in white adipose tissue. Notably, lipogenic gene expression in both white adipose tissue and liver was strongly linked to the expression of carbohydrate-responsive element-binding protein-? and to metabolic risk markers. Thus, de novo lipogenesis predicts metabolic health in humans in a tissue-specific manner and is likely regulated by glucose-dependent carbohydrate-responsive element-binding protein activation. [ABSTRACT FROM AUTHOR]

Published
2013
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