Adipocyte Development & Nutrition (ADE)
Profile of the Department
Our department examines the formation and physiological function of brown and white adipocytes. The effects of diet and aging on adipose tissue and their contribution to the development of metabolic and degenerative diseases are analyzed.
Obesity, i.e. pathological overweight, is an important risk factor for metabolic diseases such as type 2 diabetes, but also for degenerative diseases of the musculoskeletal system. Excess energy is mainly stored in white adipose tissue and leads to obesity. In contrast, brown adipose tissue displays a remarkable potential for the consumption of energy in the form of heat. Recent studies show that brown adipose tissue is also present in human adults.
Metabolic diseases such as diabetes and obesity are common side effects of old age and can be attributed, among other things, to age-related changes of the adipose tissue depots. With increasing age, the body's ability to form metabolically active brown adipocytes decreases, which causes white adipocytes to accumulate. The resulting disruption of energy metabolism could lead to further weight gain and promotion of obesity, especially in older people. In addition, degenerative diseases of the musculoskeletal system increasingly arise during aging. Sarcopenia (loss of muscle mass) and osteoporosis (bone loss) occur frequently as a result of the interplay of aging and obesity.
Aims
- Examination of stem cells and the control mechanisms that produce either white or brown fat cells
- Identification of biomarkers and messenger substances that control the formation and function of brown and white fat cells
- Research into the mechanisms by which brown or white fat cells contribute to the development of aging-related diseases, such as the metabolic syndrome and degenerative diseases of the musculoskeletal system
Team
Prof. Dr. Tim J. Schulz
Head of the Department ADEphone: +49 33 200 88 - 2110
e-mail: tim.schulz@dife.de
Significant Participations
Our department participates in the Collaborative Research Centre 1444 “Directed Cellular Self-Organisation for Advancing Bone Regeneration”, funded by the German Research Foundation (DFG), with the subproject “Bone marrow adipose tissue: Nutrient metabolism and immunomodulation during bone maintenance and regeneration”. This Collaborative Research Centre is a consortium of scientists working under the leadership of Charité – Universitätsmedizin Berlin in various research submissions based in the Berlin-Brandenburg region. It aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.
The sub-project examines the influence of adipocyte accumulation in the bone marrow: yellow bone marrow, rich in adipocytes, develops with age, but also with obesity and other metabolic diseases. Adipocyte-enriched bone marrow is a determining factor for impaired bone homeostasis and delayed bone healing. At the same time, with increasing age and overweight, there is a mild systemic inflammation, which is also caused by the cytokine release from adipocytes. Both factors, fat and inflammation, have been confirmed as negative regulators of bone healing. In this project, the regulatory mechanisms are analyzed that cause the fatty differentiation of the bone marrow and thus negatively affect the bone healing process. Our hypothesis is that different physiological factors such as nutrition and specific immune cell populations cause the accumulation of advantageous or disadvantageous bone marrow adipocytes. The possible link between bone marrow fat and reduced bone quality and impaired bone healing and the frequent occurrence in overweight and old people underlines the need for further analysis of the link between pathological metabolism and impaired bone healing, as these conditions apply to an ever-increasing population.
Publications
Aga, H., Soultoukis, G., Stadion, M., Garcia-Carrizo, F., Jähnert, M., Gottmann, P., Vogel, H., Schulz, T. J., Schürmann, A.: Distinct Adipogenic and Fibrogenic Differentiation Capacities of Mesenchymal Stromal Cells from Pancreas and White Adipose Tissue. Int. J. Mol. Sci. 23(4):2108 (2022). [Open Access]
Hauffe, R., Rath, M., Agyapong, W., Jonas, W., Vogel, H., Schulz, T. J., Schwarz, M., Kipp, A. P., Blüher, M., Kleinridders, A.: Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling. Antioxidants 11(5):862 (2022). [Open Access]
Gohlke, S., Mancini, C., Garcia-Carrizo, F., Schulz, T. J.: Loss of the ciliary gene Bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism. Faseb J. 35(11):e21966 (2021). [Open Access]
Mancini, C., Gohlke, S., Garcia-Carrizo, F., Zagoriy, V., Stephanowitz, H., Schulz, T. J.: Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways. Sci. Rep. 11(1):19928 (2021). [Open Access]
García-Carrizo, F., Picó, C., Rodríguez, A. M., Palou, A.: High-esterified pectin reverses metabolic malprogramming, improving sensitivity to adipostatic/adipokine hormones. J. Agric. Food Chem. 67, 3633-3642 (2019).
Gohlke, S., Zagoriy, V., Cuadros Inostroza, A., Méret, M., Mancini, C., Japtok, L., Schumacher, F., Kuhlow, D., Graja, A., Stephanowitz, H., Jähnert, M., Krause, E., Wernitz, A., Petzke, K.-J., Schürmann, A., Kleuser, B., Schulz, T. J.: Identification of functional lipid metabolism biomarkers of brown adipose tissue aging. Mol. Metab. 24, 1-17 (2019). [Open Access]
Quiclet, C., Dittberner, N., Gässler, A., Stadion, M., Gerst, F., Helms, A., Baumeier, C., Schulz, T. J., Schürmann, A.: Pancreatic adipocytes mediate hypersecretion of insulin in diabetes-susceptible mice. Metabolism. 97, 9-17 (2019).
Coleman, V., Sa-Nguanmoo, P., Koenig, J., Schulz, T. J., Grune, T., Klaus, S., Kipp, A. P., Ost, M.: Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling. Sci. Rep. 8:2446 (2018). [Open Access]
Graja, A., Garcia-Carrizo, F., Jank, A.-M., Gohlke, S., Ambrosi, T. H., Jonas, W., Ussar, S., Kern, M., Schürmann, A., Aleksandrova, K., Blüher, M., Schulz, T. J.: Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism. Aging Cell 17: e12810 (2018). [Open Access]
Kehm, R., König, J., Nowotny, K., Jung, T., Deubel, S., Gohlke, S., Schulz, T. J., Höhn, A.: Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system. Redox Biol. 15, 387-393 (2018). [Open Access]
Stadion, M., Schwerbel, K., Graja, A., Baumeier, C., Rödiger, M., Jonas, W., Wolfrum, C., Staiger, H., Fritsche, A., Häring, H.-U., Klöting, N., Blüher, M., Fischer-Posovszky, P., Schulz, T. J., Joost, H.-G., Vogel, H., Schürmann, A.: Increased Ifi202b/IFI16 expression stimulates adipogenesis in mice and humans. Diabetologia 61, 1167-1179 (2018). [Open Access]
Ambrosi, T. H., Scialdone, A., Graja, A., Gohlke, S., Jank, A.-M., Bocian, C., Woelk, L., Fan, H., Logan, D. W., Schürmann, A., Saraiva, L. R., Schulz, T. J.: Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 20, 771-784 (2017). [Open Access]
Steinbring, J, Graja, A., Jank, A.-M., Schulz, T. J.: Flow cytometric isolation and differentiation of adipogenic progenitor cells into brown and brite/beige adipocytes. Meth. Mol. Biol. 1566, 25-36 (2017).
Valencak, T. G., Osterrieder, A., Schulz, T. J.: Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism. Redox Biol. 12, 806-813 (2017). [Open Access]
Weitkunat, K., Stuhlmann, C., Postel, A., Rumberger, S., Fankhänel, M., Woting, A., Petzke, K. J., Gohlke, S., Schulz, T. J., Blaut, M., Klaus, S., Schumann, S.: Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice. Sci. Rep. 7: 6109 (2017). [Open Access]
Ost, M., Coleman, V., Voigt, A., van Schothorst, E. M., Keipert, S., van der Stelt, I., Ringel, S., Graja, A., Ambrosi, T., Kipp, A. P., Jastroch, M., Schulz, T. J., Keijer, J., Klaus, S.: Muscle mitochondrial stress adaptation operates independently of endogenous FGF21 action. Mol. Metab. 5, 79-90 (2016). [Open Access]
Schulz, T. J., Graja, A., Huang, T. L., Xue, R., An, D., Poehle-Kronawitter, S., Lynes, M. D., Tolkachov, A., O’Sullivan, L. E., Hirshman, M. F., Schupp, M., Goodyear, L. J., Mishina, Y., Tseng, Y. H.: Loss of BMP receptor type 1A in murine adipose tissue attenuates age-related onset of insulin resistance. Diabetologia 59, 1769-1777 (2016). [Open Access]
Galhuber, M., Michenthaler, H., Heininger, C., Reinisch, I., Nössing, C., Krstic, J., Kupper, N., Moyschewitz, E., Auer, M., Heitzer, E., Ulz, P., Birner-Gruenberger, R., Liesinger, L., Lenihan-Geels, G. N., Oster, M., Spreitzer, E., Zenezini Chiozzi, R., Schulz, T. J., Schupp, M., Madl, T., Heck, A. J. R., Prokesch, A.: Complementary omics strategies to dissect p53 signaling networks under nutrient stress. Cell. Mol. Life Sci. 79(6):326 (2022). [Open Access]
García-Carrizo, F., Galmés, S., Picó, C., Palou, A., Rodríguez, A. M.: Supplementation with the Prebiotic High-Esterified Pectin Improves Blood Pressure and Cardiovascular Risk Biomarker Profile, Counteracting Metabolic Malprogramming. J. Agric. Food Chem. 70, 13200-13211 (2022). [Open Access]
Kirschner, K. M., Foryst-Ludwig, A., Gohlke, S., Li, C., Flores, R. E., Kintscher, U., Schupp, M., Schulz, T. J., Scholz, H.: Wt1 haploinsufficiency induces browning of epididymal fat and alleviates metabolic dysfunction in mice on high-fat diet. Diabetologia 65, 528–540 (2022). [Open Access]
Oster, M., Galhuber, M., Krstic, J., Steinhoff, J. S., Lenihan-Geels, G., Wulff, S., Kiefer, M. F., Petricek, K. M., Wowro, S. J., Flores, R. E., Yang, N., Li, C., Meng, Y., Reinisch, I., Sommerfeld, M., Weger, S., Habisch, H., Madl, T., Schulz, T. J., Prokesch, A., Schupp, M.: Hepatic p53 is regulated by transcription factor FOXO1 and acutely controls glycogen homeostasis. J. Biol. Chem. 298(9):102287 (2022). [Open Access]
Reinisch, I., Klymiuk, I., Michenthaler, H., Moyschewitz, E., Galhuber, M., Krstic, J., Domingo, M., Zhang, F., Karbiener, M., Vujić, N., Kratky, D., Schreiber, R., Schupp, M., Lenihan-Geels, G., Schulz, T. J., Malli, R., Madl, T., Prokesch, A.: p53 Regulates a miRNA-Fructose Transporter Axis in Brown Adipose Tissue Under Fasting. Front. Genet. 13:913030 (2022). [Open Access]
Ruiz-Ojeda, F. J., Wang, J., Bäcker, T., Krueger, M., Zamani, S., Rosowski, S., Gruber, T., Feuchtinger, A., Schulz, T. J., Fässler, R., Müller, T. D., García-Cáceres, C., Meier, M., Blüher, M., Ussar, S.: Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis. Mol. Metab. 45:101147 (2021). [Open Access]
García-Carrizo, F., Cannon, B., Nedergaard, J., Picó, C., Dols, A., Rodríguez, A. M., Palou, A.: Regulation of thermogenic capacity in brown and white adipocytes by the prebiotic high-esterified pectin and its postbiotic acetate. Int. J. Obes. 44(3), 715–726 (2020).
McNulty, M. A., Goupil, B. A., Albarado, D. C., Castano-Martinez, T., Ambrosi, T. H., Puh, S., Schulz, T. J., Schürmann, A., Morrison, C. D., Laeger, T.: FGF21, not GCN2, influences bone morphology due to dietary protein restrictions. Bone Rep. 12:100241 (2020). [Open Access]
Shamsi, F., Xue, R., Huang, T. L., Lundh, M., Liu, Y., Leiria, L. O., Lynes, M. D., Kempf, E., Wang, C.-H., Sugimoto, S., Nigro, P., Landgraf, K., Schulz, T., Li, Y., Emanuelli, B., Kothakota, S., Williams, L. T., Jessen, N., Pedersen, S. B., Böttcher, Y., Blüher, M., Körner, A., Goodyear, L. J., Mohammadi, M., Kahn, C. R., Tseng, Y.-H.: FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis. Nat. Comm. 11:1421 (2020). [Open Access]
Leiria, L. O., Wang, C.-H., Lynes, M. D., Yang, K., Shamsi, F., Sato, M., Sugimoto, S., Chen, E. Y., Bussberg, V., Narain, N. R., Sansbury, B. E., Darcy, J., Huang, T. L., Kodani, S. D., Sakaguchi, M., Rocha, A. L., Schulz, T. J., Bartelt, A., Hotamisligil, G. S., Hirshman, M. F., van Leyen, K., Goodyear, L. J., Blüher, M., Cypess, A. M., Kiebish, M. A., Spite, M., Tseng, Y.-H.: 12-Lipoxygenase regulates cold adaptation and glucose metabolism by producing the omega-3 lipid 12-HEPE from brown fat. Cell Metab. 30, 768-783.e7 (2019).
Krstic, J., Galhuber, M., Schulz, T. J., Schupp, M., Prokesch, A.: p53 as a dichotomous regulator of liver disease: The dose makes the medicine. Int. J. Mol. Sci. 19: 921 (2018). [Open Access]
Tolkachov, A., Fischer, C., Ambrosi, T. H., Bothe, M., Han, C. T., Muenzner, M., Mathia, S., Salminen, M., Seifert, G., Thiele, M., Duda, G. N., Meijsing, S. H., Sauer, S., Schulz, T. J., Schupp, M.: Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone. Mol. Cell. Biol. 38: e00599-17 (2018). [Open Access]
Fayyaz, S., Japtok, L., Schumacher, F., Wigger, D., Schulz, T. J., Haubold, K., Gulbins, E., Völler, H., Kleuser, B.: Lysophosphatidic acid inhibits insulin signaling in primary rat hepatocytes via the LPA3 receptor subtype and is increased in obesity. Cell. Physiol. Biochem. 43, 445-456 (2017). [Open Access]
Henkel, J., Coleman, C. D., Schraplau, A., Jӧhrens, K., Weber, D., Castro, J. P., Hugo, M., Schulz, T. J., Krämer, S., Schürmann, A., Püschel, G. P.: Induction of steatohepatitis (NASH) with insulin resistance in wildtype B6 mice by a western-type diet containing soybean oil and cholesterol. Mol. Med. 23, 70-82 (2017). [Open Access]
Prokesch, A., Graef, F. A., Madl, T., Kahlhofer, J., Heidenreich, S., Schumann, A., Moyschewitz, E., Pristoynik, P., Blaschitz, A., Knauer, M., Muenzner, M., Bogner-Strauss, J. G., Dohr, G., Schulz, T. J., Schupp, M.: Liver p53 is stabilized upon starvation and required for amino acid catabolism and gluconeogenesis. FASEB J. 31, 732-742 (2017). [Open Access]
Al-Massadi, O., Porteiro, B., Kuhlow, D., Köhler, M., Gonzalez-Rellan, M. J., Garcia-Lavandeira, M., Díaz-Rodríguez, E., Quiñones, M., Senra, A., Alvarez, C. V., López, M., Diéguez, C., Schulz, T., Nogueiras, R.: Pharmacological and genetic manipulation of p53 in brown fat at adult but not embryonic stages regulates thermogenesis and body weight in male mice. Endocrinology 157, 2735-2749 (2016).
Puts, R., Ruschke, K., Ambrosi, T. H., Kadow-Romacker, A., Knaus, P., Jenderka, K. V., Raum, K.: A focused low-intensity pulsed ultrasound (FLIPUS) system for cell stimulation: physical and biological proof of principle. IEEE Trans. Ultrason. Ferroelectr. Freq. Control. 63, 91-100 (2016).
Lynes, M. D., Schulz, T. J., Pan, A. J., Tseng, Y. H.: Disruption of insulin signaling in myf5-expressing progenitors leads to marked paucity of brown fat but normal muscle development. Endocrinology 156, 1637-1647 (2015). [Open Access]
Zhang, H., Guan, M., Townsend, K. L., Huang, T. L., An, D., Yan, X., Xue, R., Schulz, T. J., Winnay, J., Mori, M., Hirshman, M. F., Kristiansen, K., Tsang, J. S., White, A. P., Cypess, A. M., Goodyear, L. J., Tseng, Y. H.: MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network. EMBO Rep. 16, 1378-1393 (2015). [Open Access]
Burkhardt, L.-M., Bucher, C. H., Löffler, J., Rinne, C., Duda, G. N., Geissler, S., Schulz, T. J., Schmidt-Bleek, K.: The benefits of adipocyte metabolism in bone health and regeneration. Frontiers Cell Develop. Biol. 11:1104709 (2023). [Open Access]
Bravenboer, N., Bredella, M. A., Chauveau, C., Corsi, A., Douni, E., Ferris, W. F., Riminucci, M., Robey, P. G., Rojas-Sutterlin, S., Rosen, C., Schulz, T. J., Cawthorn, W. P.: Standardised Nomenclature, Abbreviations, and Units for the Study of Bone Marrow Adiposity: Report of the Nomenclature Working Group of the International Bone Marrow Adiposity Society. Front. Endocrinol. 10:923 (2020). [Open Access]
Krstic, J., Reinisch, I., Schupp, M., Schulz, T. J., Prokesch, A.: p53 functions in adipose tissue metabolism and homeostasis. Int. J. Mol. Sci. 19(9): 2622 (2018). [Open Access]
Ambrosi, T. H., Schulz, T. J.: The emerging role of bone marrow adipose tissue in bone health and dysfunction. J. Mol. Med. (Berl) 95, 1291-1301 (2017).
Grgurevic, L., Christensen, G. L., Schulz, T. J., Vukicevic, S.: Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism. Cytokine Growth Factor Rev. 27, 105-118 (2016).
Graja, A., Schulz, T. J.: Mechanisms of aging-related impairment of brown adipocyte development and function. Gerontology 61, 211-217 (2015). [Open Access]
Graja, A., Gohlke, S., Schulz, T. J.: Aging of Brown and Beige/Brite Adipose Tissue. In: Pfeifer, A., Klingenspor, M., Herzig, S. (eds.) Brown Adipose Tissue (Handb. Exp. Pharmacol.; 251), pp. 55-72 (2019).
Boosting Health by Nutrition Research.
DIfE is a member of the
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EUROPEAN UNION
European Regional
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