Physiology of Energy Metabolism (EST)
Profile of the Department
An imbalanced energy homeostasis can lead to metabolic dysfunctions such as obesity and diabetes that can decrease life expectancy. We are trying to better understand the regulation of energy balance by investigating the physiological mechanisms that regulate energy flow from transformation of food energy intake, distribution to the various organs down to cellular energy expenditure. We use mainly animal models to study the interactions and cross talk of important organs such as intestine, liver, adipose tissue, and skeletal muscle. Our focus is on metabolic mediators affecting organ and tissue interactions and energy homeostasis. This includes nutrients such as amino acids, fibers and their metabolites (for example short chain fatty acids produced by bacterial fermentation in the gut) as well as cytokines with para-, auto- and endocrine actions. Regarding cytokines, we are currently focusing on the metabolic role of FGF21 (fibroblast growth factor 21) und GDF15 (growth differentiation factor 15). These are cytokines with endocrine action that can be induced by various types of cellular stress in different cell types and tissue, for example by mitochondrial dysfunction in skeletal muscle. They are secreted into the circulation where they were found to be increased with aging making them candidates for biomarkers of aging.
Team
Prof. Dr. Susanne Klaus
Head of the Department ESTphone: +49 33 200 88 - 2326
e-mail: klaus@dife.de
Publications
Bishop, C. A., Machate, T., Henkel, J., Schulze, M. B., Klaus, S., Piepelow, K.: Heptadecanoic Acid Is Not a Key Mediator in the Prevention of Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice. Nutrients 15(9):2052 (2023). [Open Access]
Bishop, C. A., Machate, T., Henning, T., Henkel, J., Püschel, G., Weber, D., Grune, T., Klaus, S., Weitkunat, K.: Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle. Nutr. Diabetes 12(1):20 (2022). [Open Access]
Gil, C. I., Coull, B. M., Jonas, W., Lippert, R., Ost, M., Klaus, S.: Mitochondrial stress-induced GDF15-GFRAL axis promotes anxiety-like behavior and CRH-dependent anorexia. Life Sci. Alliance 5(11):e202201495 (2022). [Open Access]
Herpich, C., Lehmann, S., Kochlik, B., Kleinert, M., Klaus, S., Müller-Werdan, U., Norman, K.: The Effect of Dextrose or Protein Ingestion on Circulating Growth Differentiation Factor 15 and Appetite in Older Compared to Younger Women. Nutrients 14(19):4066 (2022). [Open Access]
Herpich, C., Franz, K., Klaus, S., Müller-Werdan, U., Ost, M., Norman, K.: Age-related fatigue is associated with reduced mitochondrial function in peripheral blood mononuclear cells. Exp. Gerontol. 144:111177 (2021).
Herpich, C., Franz, K., Ost, M., Otten, L., Coleman, V., Klaus, S., Müller-Werdan, U., Norman, K.: Associations between serum GDF15 concentrations, muscle mass and strength show sex-specific differences in older hospital patients. Rejuv. Res. 24(1), 14-19 (2021).
Herpich, C., Haß, U., Kochlik, B., Franz, K., Laeger, T., Klaus, S., Bosy-Westphal, A., Norman, K.: Postprandial dynamics and response of fibroblast growth factor 21 in older adults. Clin. Nutr. 40(6), 3765-3771 (2021).
Meng, L., Coleman, V., Zhao, Y., Ost, M., Voigt, A., Bunschoten, A., Keijer, J., Teerds, K., Klaus, S.: Pseudo-Starvation Driven Energy Expenditure Negatively Affects Ovarian Follicle Development. Int. J. Mol. Sci. 22(7):3557 (2021). [Open Access]
Weitkunat, K., Bishop, C. A., Wittmüss, M., Machate, T., Schifelbein, T., Schulze, M. B., Klaus, S.: Effect of Microbial Status on Hepatic Odd-Chain Fatty Acids Is Diet-Dependent. Nutrients 13(5):1546 (2021). [Open Access]
Bishop, C. A., Schulze, M. B., Klaus, S., Weitkunat, K.: The branched-chain amino acids valine and leucine have differential effects on hepatic lipid metabolism. Faseb J. 34(7), 9727-9739 (2020). [Open Access]
Ost, M., Igual Gil, C., Coleman, V., Keipert, S., Efstathiou, S., Vidic, V., Weyers, M., Klaus, S.: Muscle-derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress. EMBO Rep. 21(3):e48804 (2020). [Open Access]
Weindl, I., Ost, M., Wiedmer, P., Schreiner, M., Neugart, S., Klopsch, R., Kühnhold, H., Kloas, W., Henkel, I. M., Schlüter, O., Bußler, S., Bellingrath-Kimura, S. D., Ma, H., Grune, T., Rolinski, S., Klaus, S.: Sustainable food protein supply reconciling human and ecosystem health: A Leibniz Position. Global Food Security 25:100367 (2020). [Open Access]
Xu, C., Markova, M., Seebeck, N., Loft, A., Hornemann, S., Gantert, T., Kabisch, S., Herz, K., Loske, J., Ost, M., Coleman, V., Klauschen, F., Rosenthal, A., Lange, V., Machann, J., Klaus, S., Grune, T., Herzig, S., Pivovarova-Ramich, O., Pfeiffer, A. F. H.: High-protein diet more effectively reduces hepatic fat than low-protein diet despite lower autophagy and FGF21 levels. Liver Inter. 40(12), 2982-2997 (2020). [Open Access]
Fernando, R., Drescher, C., Deubel, S., Jung, T., Ost, M., Klaus, S., Grune, T., Castro, J. P.: Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage. Exp. Gerontol. 117, 45-52 (2019).
Franz, K., Ost, M., Otten, L., Herpich, C., Coleman, V., Endres, A.-S., Klaus, S., Müller-Werdan, U., Norman, K.: Higher serum levels of fibroblast growth factor 21 in old patients with cachexia. Nutrition 63-64, 81-86 (2019).
Gil, C. I., Ost, M., Kasch, J., Schumann, S., Heider, S., Klaus, S.: Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice. Sci Rep 9, 20120 (2019). [Open Access]
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]
Kasch, J., Kanzleiter, I., Saussenthaler, S., Schürmann, A., Keijer, J., van Schothorst, E., Klaus, S., Schumann, S.: Insulin sensitivity linked skeletal muscle Nr4a1 DNA methylation is programmed by the maternal diet and modulated by voluntary exercise in mice. J. Nutr. Biochem. 57, 86-92 (2018).
Kessler, K., Hornemann, S., Petzke, K. J., Kemper, M., Markova, M., Rudovich, N., Grune, T., Kramer, A., Pfeiffer, A. F. H., Pivovarova-Ramich, O.: Diurnal distribution of carbohydrates and fat affects substrate oxidation and adipokine secretion in humans. Am. J. Clin. Nutr. 108, 1209-1219 (2018).
Endo, T., Ogasawara, H., Hayasaka, M., Hotta, Y., Kimura, O., Petzke, K. J.: Correlations between mercury concentration, and stable isotope ratios of carbon and nitrogen of amino acids in scalp hair from whale meat eaters and heavy fish eaters. Rapid Commun. Mass Spectrom. 31, 745-752 (2017).
Fuller, B. T., Petzke, K. J.: The dietary protein paradox and threonine 15 N-depletion: Pyridoxal-5’-phosphate enzyme activity as a mechanism for the δ15 N trophic level effect. Rapid Commun. Mass Spectrom. 31, 705-718 (2017).
Kasch, J., Schumann, S., Schreiber, S., Klaus, S., Kanzleiter, I.: Beneficial effects of exercise on offspring obesity and insulin resistance are reduced by maternal high-fat diet. PLoS ONE 12(2):e0173076, Correction: PLOS ONE 12(3): e0175100 (2017). [Open Access]
Kessler, K., Hornemann, S., Petzke, K. J., Kemper, M., Kramer, A., Pfeiffer, A. F. H., Pivovarova, O., Rudovich, N.: The effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans: a randomized controlled trial. Sci. Rep. 7: 44170 (2017). [Open Access]
Markova, M., Pivovarova, O., Hornemann, S., Sucher, S., Frahnow, T., Wegner, K., Machann, J., Petzke, K. J., Hierholzer, J., Lichtinghagen, R., Herder, C., Carstensen-Kirberg, M., Roden, M., Rudovich, N., Klaus, S., Thomann, R., Schneeweiss, R., Rohn, S., Pfeiffer, A. F. H.: Isocaloric diets high in animal or plant protein reduce liver fat and inflammation in individuals with type 2 diabetes. Gastroenterology 152, 571–585 (2017).
Weitkunat, K., Schumann, S., Nickel, D., Hornemann, S., Petzke, K. J., Schulze, M. B., Pfeiffer, A. F. H., Klaus, S.: Odd-chain fatty acids as a biomarker for dietary fiber intake: a novel pathway for endogenous production from propionate. Am. J. Clin. Nutr. 105, 1544-1551 (2017).
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]
Weitkunat, K., Schumann, S., Nickel, D., Kappo, K. A., Petzke, K. J., Kipp, A. P., Blaut, M., Klaus, S.: Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity. Mol. Nutr. Food Res. 60, 2611-2621 (2016). [Open Access]
Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K. J., Jove, M., Pamplona, R., Portero-Otin, M., Keijer, J., Klaus, S.: Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux. FASEB J. 29, 1314-1328 (2015). [Open Access]
Voigt, A., Katterle, Y., Kahle, M., Kluge, R., Schürmann, A., Joost, H. G., Klaus, S.: Skeletal muscle mitochondrial uncoupling prevents diabetes but not obesity in NZO mice, a model for polygenic diabesity. Genes Nutr. 10(6):57 (2015). [Open Access]
Voigt, A., Ribot, J., Sabater, A. G., Palou, A., Bonet, M. L., Klaus, S.: Identification of Mest/Peg1 gene expression as a predictive biomarker of adipose tissue expansion sensitive to dietary anti-obesity interventions. Genes Nutr. 10(5):477 (2015). [Open Access]
Weitkunat, K., Schumann, S., Petzke, K. J., Blaut, M., Loh, G., Klaus, S.: Effects of dietary inulin on bacterial growth, short-chain fatty acid production and hepatic lipid metabolism in gnotobiotic mice. J. Nutr. Biochem. 26, 929-937 (2015).
Woting, A., Pfeiffer, N., Hanske, L., Loh, G., Klaus, S., Blaut, M.: Alleviation of high fat diet-induced obesity by oligofructose in gnotobiotic mice is independent of presence of Bifidobacterium longum. Mol. Nutr. Food Res. 59, 2267-2278 (2015). [Open Access]
Hou, H.-W., Bishop, C. A., Huckauf, J., Broer, I., Klaus, S., Nausch, H., Buyel, J. F.: Seed- and leaf-based expression of FGF21-transferrin fusion proteins for oral delivery and treatment of non-alcoholic steatohepatitis. Front. Plant Sci. 13:998596 (2022). [Open Access]
Münzker, J., Haase, N., Till, A., Sucher, R., Haange, S. B., Nemetschke, L., Gnad, T., Jäger, E., Chen, J., Riede, S. J., Chakaroun, R., Massier, L., Kovacs, P., Ost, M., Rolle-Kampczyk, U., Jehmlich, N., Weiner, J., Heiker, J. T., Klöting, N., Seeger, G., Morawski, M., Keitel, V., Pfeifer, A., von Bergen, M., Heeren, J., Krügel, U., Fenske, W. K.: Functional changes of the gastric bypass microbiota reactivate thermogenic adipose tissue and systemic glucose control via intestinal FXR-TGR5 crosstalk in diet-induced obesity. Microbiome 10(1):96 (2022). [Open Access]
Wei, X., Franke, J., Ost, M., Wardelmann, K., Boerno, S., Timmermann, B., Meierhofer, D., Kleinridders, A., Klaus, S., Stricker, S.: Cell autonomous requirement of Neurofibrimin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis. J. Cachex. Sarc. Mus. 11(6), 1758-1778 (2020). [Open Access]
Wolfram, T., Schwarz, M., Reuß, M., Lossow, K., Ost, M., Klaus, S., Schwerdtle, T., Kipp, A. P.: N-Acetylcysteine as Modulator of the Essential Trace Elements Copper and Zinc. Antioxid. 9(11):1117 (2020). [Open Access]
Graf, D., Weitkunat, K., Dötsch, A., Liebisch, G., Döring, M., Krüger, R., Vatareck, E., von Coburg, E., Loh, G., Watzl, B.: Specific wheat fractions influence hepatic fat metabolism in diet-induced obese mice. Nutrients 11(10): e2348 (2019). [Open Access]
Yan, X., Wang, Z., Bishop, C. A., Weitkunat, K., Feng, X., Tarbier, M., Luo, J., Friedländer, M. R., Burkhardt, R., Klaus, S., Willnow, T. E., Poy, M. N.: Control of hepatic gluconeogenesis by Argonaute2. Mol. Metab. 18, 15-24 (2018). [Open Access]
Keipert, S., Kutschke, M., Ost, M., Schwarzmayr, T., van Schothorst, E. M., Lamp, D., Brachthäuser, L., Hamp, I., Mazibuko, S. E., Hartwig, S., Lehr, S., Graf, E., Plettenburg, O., Neff, F., Tschöp, M. H., Jastroch, M.: Long-term cold adaptation does not require FGF21 or UCP1. Cell Metab. 26, 437-446.e5 (2017). [Open Access]
Deveaux, A., Fouillet, H., Petzke, K. J., Hermier, D., André, E., Bunouf, P., Lantoine-Adam, F., Benamouzig, R., Mathé, V., Huneau, J. F., Mariotti, F.: A slow- compared with a fast-release form of oral arginine increases its utilization for nitric oxide synthesis in overweight adults with cardiometabolic risk factors in a randomized controlled study. J. Nutr. 146, 1322-1329 (2016). [Open Access]
Derous, D., Kelder, T., van Schothorst, E. M., van Erk, M., Voigt, A., Klaus, S., Keijer, J., Radonjic, M.: Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet. Genes Nutr. 10(4):22 (2015). [Open Access]
Kelder, T., Summer, G., Caspers, M., van Schothorst, E. M., Keijer, J., Duivenvoorde, L., Klaus, S., Voigt, A., Bohnert, L., Pico, C., Palou, A., Bonet, M. L., Dembinska-Kiec, A., Malczewska-Malec, M., Kieć-Wilk, B., del Bas, J. M., Caimari, A., Arola, L., van Erk, M., van Ommen, B., Radonjic, M.: White adipose tissue reference network: a knowledge resource for exploring health-relevant relations. Genes Nutr. 10(1):439 (2015). [Open Access]
Schering, L., Hoene, M., Kanzleiter, T., Jähnert, M., Wimmers, K., Klaus, S., Eckel, J., Weigert, C., Schürmann, A., Maak, S., Jonas, W., Sell, H.: Identification of novel putative adipomyokines by a cross-species annotation of secretomes and expression profiles. Arch. Physiol. Biochem. 121, 194-205 (2015).
Johann, K., Kleinert, M., Klaus, S.: The Role of GDF15 as a Myomitokine. Cells 10(11):2990 (2021). [Open Access]
Klaus, S., Igual Gil, C., Ost, M.: Regulation of diurnal energy balance by mitokines. Cell. Mol. Life Sci. 78, 3369–3384 (2021). [Open Access]
Klaus, S., Ost, M.: Mitochondrial uncoupling and longevity - A role for mitokines?. Exp. Gerontol. 130:110796 (2020).
Norman, K., Klaus, S.: Veganism, aging and longevity: new insight into old concepts. Curr. Opin. Clin. Nutr. Metab. Care 23(2), 145-150 (2020).
Klaus, S., Pfeiffer, A. F. H., Boeing, H., Laeger, T., Grune, T.: The protein paradox: how much dietary protein is good for health?. Ernaehr. Umsch. 65, 42-47 (2018). [Open Access]
Ost, M., Doerrier, C., Gama-Perez, P., Moreno-Gomez, S.: Analysis of mitochondrial respiratory function in tissue biopsies and blood cells. Curr. Opin. Clin. Nutr. Metab. Care 21, 336-342 (2018).
Müller-Werdan, U., Nuding, S. Ost, M.: Assessing inflammageing. Curr. Opin. Clin. Nutr. Metab. Care 20, 346-348 (2017).
Ost, M., Keipert, S., Klaus, S.: Targeted mitochondrial uncoupling beyond UCP1 - the fine line between death and metabolic health. Biochimie 134, 77-85 (2017).
Ost, M., Coleman, V., Kasch, J., Klaus, S.: Regulation of myokine expression: Role of exercise and cellular stress. Free Radic. Biol. Med. 98, 78-89 (2016).
Bouillaud, F., Casteilla, L., Klaus, S., Miroux, B.: UCP1: 40 years and beyond. Biochemie 134, 1-2 (Editorial) (2017).
Weitkunat, K., Schumann, S., Klaus, S.: Reply to TM Venäläinen et al.. Am. J. Clin. Nutr. 106, 954-955 (2017).
Petzke, K. J.: Stable isotopes, diet, and diabetes incidence. Am. J. Clin. Nutr. 101, 687-688 (Letter to editor) (2015). [Open Access]
Boosting Health by Nutrition Research.
DIfE is a member of the
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EUROPEAN UNION
European Regional
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