B1 - Heterogeneity of Adipose Tissue

The majority of patients with obesity has impaired adipose tissue (AT) function which is characterized by adipocyte hypertrophy, a variety of stress and inflammatory processes within AT and adverse adipokine secretion. Ectopic fat accumulation may be considered to be a consequence of AT dysfunction. This project focusses on the concept that gene–environment interactions determine AT function. In project B1, we identified novel candidate genes for ectopic (including visceral) fat accumulation and AT dysfunction. In addition, genetic variants in several previously unrecognized genes associated with fat distribution have been reported from genome-wide association studies. However, the function of these genes and the mechanisms underlying their association with adverse fat distribution and AT dysfunction are still not entirely understood. In this project, we aim to test the hypothesis that selected candidate genes of fat distribution (e.g. HoxC9, ADCY5, BMP-4), adipose tissue function (e.g. Atg7, PSRC1, BCAT1/2, E2F1) as well as adipokines (e.g. asprosin, BMP-2, Trib1, osteocalcin) contribute to heterogeneity of AT. One aim of the project is therefore to characterize the function of these candidate molecules underlying the biological heterogeneity of AT. We further aim to characterize the mechanisms how environmental compounds, selected from preliminary human AT accumulation data may contribute to obesity and AT dysfunction in diet-induced obesity mouse model exposure studies. Using a human AT bank of >2,300 paired omental and subcutaneous AT samples from well-phenotyped lean and obese individuals, different weight loss intervention studies, extreme phenotypes (e.g. insulin sensitive obesity, lipodystrophy, cachexia), in vitro approaches, treatment of animal models with recombinant adipokines, as well as conditional knockout mouse models (AT-specific HoxC9-KO, ADCY5-KO), we aim to identify the role of these candidate molecules in AT biology, fat distribution, and in the pathogenesis of obesity.

Figure 1. Model for the pathogenesis of adipose tissue dysfunction. Gene-environment interactions may play a role both as causative factors for obesity development itself and for the dissociation into subphenotypes of physiologic (predominantly subcutaneous, insulin sensitive) or pathologic (visceral, ectopic) fat accumulation. From the latter a sequence of pathogenic factors causes either stepwise or directly impaired adipose tissue function. Individuals with metabolically healthy obesity are characterized by lower visceral fat mass, more abdominal subcutaneous fat, lower liver and skeletal muscle fat, smaller adipocytes and less macrophage infiltration of visceral adipose tissue compared to patients with high metabolic risk obesity. Example pictures and MRI scans of the abdominal region at L4. Histological slides of omental adipose tissue from either metabolically healthy or high risk obese individuals.

Schmidleithner L, Thabet Y, Schönfeld E, Köhne M, Sommer D, Abdullah Z, Sadlon T, Osei-Sarpong C, Subbaramaiah K, Copperi F, Haendler K, Varga T, Schanz O, Bourry S, Bassler K, Krebs W, Peters AE, Baumgart AK, Schneeweiss M, Klee K, Schmidt SV, Nüssing S, Sander J, Ohkura N, Waha A, Sparwasser T, Wunderlich FT, Förster I, Ulas T, Weighardt H, Sakaguchi S, Pfeifer A, Blüher M, Dannenberg AJ, Ferreirós N, Muglia LJ, Wickenhauser C, Barry SC, Schultze JL, Beyer M. Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction. Immunity. 2019 Apr 15. pii: S1074-7613(19)30131-1.

Mancini G, Pirruccio K, Yang X, Blücher M, Rodeheffer M, Horvath TL., Mitofusin 2 in Mature Adipocytes Controls Adiposity and Body Weight. Cell Rep. 2019 Mar 12;26(11):2849-2858.e4.

Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019 Feb 27.

Goldstein N, Haim Y, Mattar P, Hadadi-Bechor S, Maixner N, Kovacs PBlüher MRudich A. Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes. Adipocyte. 2019 Jan 24.

Kosacka J, Woidt K, Toyka KV, Paeschke S, Klöting NBechmann IBlüher M, Thiery J, Ossmann S, Baum P, Nowicki M. The role of dietary non-heme iron load and peripheral nerve inflammation in the development of peripheral neuropathy (PN) in obese non-diabetic leptin-deficient ob/ob mice. Neurol Res. 2019 Jan 13:1-13.

Giusepponi ME, Kern M, Chakaroun R, Wohland T, Kovacs P, Dietrich A, Schön MR, Krohn K, Pucci M, Polidori C, Micioni Di Bonaventura MV, Stumvoll MBlüher M, Cifani C, Klöting N. Gene expression profiling in adipose tissue of Sprague Dawley rats identifies olfactory receptor 984 as a potential obesity treatment target. Biochem Biophys Res Commun. 2018 Nov 2;505(3):801-806.

Rohde K, Keller M, la Cour Poulsen L, Blüher M, Kovacs P, Böttcher Y. Genetics and epigenetics in obesity. Metabolism. 2018 Nov 3. pii: S0026-0495(18)30225-7.

Schmidt E, Dhaouadi I, Gaziano I, Oliverio M, Klemm P, Awazawa M, Mitterer G, Fernandez-Rebollo E, Pradas-Juni M, Wagner W, Hammerschmidt P, Loureiro R, Kiefer C, Hansmeier NR, Khani S, Bergami M, Heine M, Ntini E, Frommolt P, Zentis P, Ørom UA, Heeren J, Blüher M, Bilban M, Kornfeld JW. LincRNA H19 protects from dietary obesity by constraining expression of monoallelic genes in brown fat. Nat Commun. 2018 Sep 6;9(1):3622

Spiller S, Blüher M, Hoffmann R. Plasma levels of free fatty acids correlate with type 2 diabetes mellitus. Diabetes Obes Metab. 2018 Jun 25.

Hollenbach M, Klöting N, Sommerer I, Lorenz J, Heindl M, Kern M, Mössner J, Blüher M, Hoffmeister A. p8 deficiency leads to elevated pancreatic beta cell mass but does not contribute to insulin resistance in mice fed with high-fat diet. PLoS One. 2018 Jul 24

Krüger J, Berger C, Weidle K, Schleinitz D, Tönjes A, Stumvoll MBlüher M, Kovacs P, Klöting N. Metabolic effects of genetic variation in the human REPIN1 gene. Circ Genom Precis Med. 2018 May;11(5):e001992.

Langhardt J, Flehmig G, Klöting N, Lehmann S, Ebert T, Kern M, Schön MR, Gärtner D, Lohmann T, Dressler M, Fasshauer MKovacs PStumvoll M, Dietrich A, Blüher M. Effects of Weight Loss on Glutathione Peroxidase 3 Serum Concentrations and Adipose Tissue Expression in Human Obesity. Obes Facts. 2018;11(6):475-490.

Spiller S, Li Y, Blüher M, Welch L, Hoffmann R. Diagnostic Accuracy of Protein Glycation Sites in Long-Term Controlled Patients with Type 2 Diabetes Mellitus and Their Prognostic Potential for Early Diagnosis. Pharmaceuticals (Basel). 2018 Apr 30;11(2)

Ghorpade DS, Ozcan L, Zheng Z, Nicoloro SM, Shen Y, Chen E, Blüher M, Czech MP, Tabas I. Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature. 2018 Mar 29;555(7698):673-677.

Gross A, Tönjes A, Scholz M. On the impact of relatedness on SNP association analysis. BMC Genet. 2017;18:104.

Gepner Y, Shelef I, Schwarzfuchs D, Cohen N, Bril N, Rein M, Tsaban G, Zelicha H, Yaskolka Meir A, Tene L, Sarusy B, Rosen P, Hoffman JR, Stout JR, Thiery J, Ceglarek U, Stumvoll M, Blüher M, Stampfer MJ, Shai I. Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial. PLoS One. 2017;12:e0188431.

Tönjes A, Scholz M, Krüger J, Krause K, Schleinitz D, Kirsten H, Gebhardt C, Marzi C, Grallert H, Ladenvall C, Heyne H, Laurila E, Kriebel J, Meisinger C, Rathmann W, Gieger C, Groop L, Prokopenko I, Isomaa B, Beutner F, Kratzsch J, Fischer-Rosinsky A, Pfeiffer A, Krohn K, Spranger J, Thiery J, Blüher M, Stumvoll M, Kovacs P. Genome wide meta-analysis identifies novel determinants of circulating serum progranulin. Hum Mol Genet. 2017; Epub ahead of print.

Gepner Y, Shelef I, Schwarzfuchs D, Zelicha H, Tene L, Yaskolka Meir A, Tsaban G, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Komy O, Wolak A, Chassidim Y, Golan R, Avni-Hassid H, Bilitzky A, Sarusi B, Goshen E, Shemesh E, Henkin Y, Stumvoll M, Blüher M, Thiery J, Ceglarek U, Rudich A, Stampfer MJ, Shai I. Effect of distinct lifestyle interventions on mobilization of fast storage pools: the CENTRAL MRI randomized control trial. Circulation. 2017; Epub ahead of print.

Zieger K, Weiner J, Kunath A, Gericke M, Krause K, Kern M, Stumvoll M, Klöting N, Blüher M, Heiker JT. Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high-fat diet induced obesity by counteracting adipose tissue inflammation in vivo. Cell Mol Life Sci. 2017; Epub ahead of print.

Rohde K, Klös M, Hopp L, Liu X, Keller M, Stumvoll M, Dietrich A, Schön MR, Gärtner D, Lohmann T, Dreßler M, Kovacs P, Binder H, Blüher M, Böttcher Y. IRS1 DNA promoter methylation and expression in human adipose tissue are related to fat distribution and metabolic traits. Sci Rep. 2017;7:12369.

Tsaban G, Wolak A, Avni-Hassid H, Gepner Y, Shelef I, Henkin Y, Schwarzfuchs D, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Tene L, Zelicha H, Yaskolka-Meir A, Komy O, Bilitzky A, Chassidim Y, Ceglarek U, Stumvoll M, Blüher M, Thiery J, Dicker D, Rudich A, Stamper MJ, Shai I. Dynamics of intrapericardial and extrapericardial fat tissues during long-term, dietary-induced, moderate weight loss. Am J Clin Nutr. 2017;106:984-95.

Hesselbarth N, Kunath A, Kern M, Gericke M, Mejhert N, Ryden M, Stumvoll M, Blüher M, Klöting N. Repin1 deficiency in adipose tissue improves whole-body insulin sensitivity, and lipid metabolism. Int J Obes (Lond). 2017; Epub ahead of print.

Haim Y, Blüher M, Konrad D, Goldstein N, Klöting N, Harman-Boehm I, Kirshtein B, Ginsberg D, Tarnovscki T, Gepner Y, Shai I, Rudich A. ASK1 (MAP3K5) is transcriptionally upregulated by E2F1 in adipose tisue in obesity, molecularly defining a human dys-metabolic obese phenotype. Mol Metab. 2017;6:725-36.

Kralisch S, Hoffmann A, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M, Ebert T. The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus. Diabetes Metab. 2017; Epub ahead of print.

Zieger K, Weiner J, Krause K, Schwarz M, Kohn M, Stumvoll M, Blüher M, Heiker JT. Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via inhibition of NFkB pathway. Mol Cell Endocrinol. 2017; Epub ahead of print.

Weiner J, Rohde K, Krause K, Zieger K, Klöting N, Kralisch S, Kovacs P, Stumvoll M, Blüher M, Böttcher Y, Heiker JT. Brown adipose tissue (BAT) specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation. Mol Metab. 2017;6:482-93.

Kralisch S, Hoffmann A, Klöting N, Bachmann A, Kratzsch J, Stolzenburg JU, Dietel A, Beige J, Anders M, Bast I, Blüher M, Zhang MZ, Harris RC, Stumvoll M, Fasshauer M, Ebert T. FSTL3 is increased in renal dysfunction. Nephrol Dial Transplant. 2017;32:1637-44.

Braune J, Weyer U, Matz-Soja M, Hobusch C, Kern M, Kunath A, Klöting N, Kralisch S, Blüher M, Gebhardt R, Zavros Y, Bechmann I, Gericke M. Hedgehog sinaling in myeloid cells impacts on body weight, adipose tissue inflammation and glucose metabolism. Diabetologia. 2017;60:889-99.

Keller M, Hopp L, Liu X, Wohland T, Rohde K, Cancello R, Klös M, Bacos K, Kern M, Eichelmann F, Dietrich A, Schön MR, Gärtner D, Lohmann T, Dreßler M, Stumvoll M, Kovacs P, DiBlasio AM, Ling C, Binder H, Blüher M, Böttcher Y. Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity. Mol Metab. 2016;6:86-100

Guiu-Jurado E, Unthan M, Böhler N, Kern M, Landgraf K, Dietrich A, Schleinitz D, Ruschke K, Klöting N, Faßhauer M, Tönjes A, Stumvoll M, Körner A, Kovacs P, Blüher M. Bone morphogenetic protein 2 (BMP2) may contribute to partition of energy storage into visceral and subcutaneous fat depots. Obesity (Silver Spring). 2016;24:2092-100.

Lazaridis I, Nadel D, Rollefson G, Merrett DC, Rohland N, Mallick S, Fernandes D, Novak M, Gamarra B, Sirak K, Connell S, Stewardson K, Harney E, Fu Q, Gonzales-Fortes G, Jones ER, Roodenberg SA, Lengyel G, Bocquentin F, Gasparian B, Monge JM, Gregg M, Eshed V, Mizrahi AS, Meiklejohn C, Gerritsen F, Bejenaru L,Blüher M, Campbell A, Cavalleri G, Comas D, Froguel P, Gilbert E, Kerr SM, Kovacs P, Krause J, McGettigan D, Merrigan M, Merriwether DA, O'Reilly S, Richards MB, Semino  O, Shamoon-Pour M, Stefanescu G, Stumvoll M, Tönjes A, Torroni A, Wilson JF, Yengo L, Hovhannisyan NA, Patterson N, Pinhasi R, Reich D. Genomic insights into the origin of farming in the ancient Near East. Nature. 2016;536:419-24.

Hankir MK, Kranz M, Gnad T, Weiner J, Wagner S, Deuther-Conrad W, Bronisch F, Steinhoff K, Luthardt J, Klöting N, Hesse S, Seibyl JP, Sabri O, Heiker JT, Blüher M, Pfeifer A, Brust P, Fenske WK. A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016;8:796-812.

Pfeiffer S, Krüger J, Maierhofer A, Böttcher Y, Klöting N, El Hajj N, Schleinitz D, Schön MR, Dietrich A, Fasshauer M, Lohmann T, Dreßler M, Stumvoll M, Haaf T, Blüher M, Kovacs P. Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction. Sci Rep. 2016;6:27969.

Stelzner K, Herbert D, Popkova Y, Lorz A, Schiller J, Gericke M, Klöting N, Blüher M, Franz S, Simon JC, Saalbach A. Free fatty acids sensitize dendritic cells to amplify TH1/TH17-immune responses. Eur J Immunol. 2016;46:2043-53.

Hoffmann A, Manjowk GM, Wagner V, Klöting N, Ebert T, Jessnitzer B, Lössner U, Stukenborg JB, Blüher M, Stumvoll M, Söder O, Svechnikov K, Fasshauer M, Kralisch S. Leptin within the subphysiological to physiological range dose-dependently improves male reproductive function in an obesity mouse model. Endocrinology. 2016;157:2461-8.

Baum P, Kosacka J, Estrela-Lopis I, Woidt K, Serke H, Paeschke S, Stockinger M, Klöting N, Blüher M, Dorn M, Classen J, Thiery J, Bechmann I, Toyka KV, Nowicki M. The role of nerve inflammation and exogenous iron load in experimental peripheral diabetic neuropathy (PDN). Metabolism. 2016;65:391-405.

Brune JE, Kern M, Kunath A, Flehmig G, Schön MR, Lohmann T, Dressler M, Dietrich A, Fasshauer M, Kovacs P, Stumvoll M, Blüher M, Klöting N. Fat depot-specific expression of HOXC9 and HOXC10 may contribute to adverse fat distribution and related metabolic traits. Obesity (Silver Spring). 2016;24:51-9.

Klöting N, Hesselbarth N, Gericke M, Kunath A, Biemann R, Chakaroun R, Kosacka J, Kovacs P, Kern M, Stumvoll M, Fischer B, Rolle-Kampczyk U, Feltens R, Otto W, Wissenbach DK, von Bergen M, Blüher M. Di-(2 Ehtylhexyl)-Phtalate (DEHP) causes impaired adipocyte function and alters serum metabolites. PLoS One. 2015;10:e0143190.

Voisin S, Almen MS, Zheleznyakova GY, Lundberg L, Zarei S, Castillo S, Eriksson FE, Nilsson EK, Blüher M, Böttcher Y, Kovacs P, Klovins J, Rask-Andersen M, Schiöth HB. Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers. Genome Med. 2015;7:103.

Mardinoglu A, Heiker JT, Gärtner D, Björnson E, Schön MR, Flehmig G, Klöting N, Krohn K, Fasshauer M, Stumvoll M, Nielsen J, Blüher M. Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue. Sci Rep. 2015;5:14841.

Winkler TW, Justice AE, Graff M, [...], Blüher M, [...], Kovacs P, [...], Stumvoll M, [...], Loos RJ. The influence of age and sex on genetic associations with adult body size and shape: A large-scale genome-wide interaction study. PLoS One. 2015;11:e1005378.

Haim Y, Blüher M, Slutsky N, Goldstein N, Klöting N, Harman-Boehm I, Kirshstein B, Ginsberg D, Gericke M, Guiu Jurado E, Kovsan J, Tarnovscki T, Kachko L, Bashan N, Gepner Y, Shai I, Rudich A. Elevated autophagy gene expression in adipose tissue of humans: A potential non-cell-cycle-dependent function of E2F1. Autophagy. 2015;11:2074-88.

Mueller K, Möller HE, Horstmann A, Busse-Voigt FP, Lepsien J, Blüher M, Stumvoll M, Villringer A, Pleger B. Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity. Front Hum Neurosci. 2015;9:372.

Kosacka J, Kern M, Klöting N, Paeschke S, Rudich A, Haim Y, Gericke M, Serke H, Stumvoll M, Bechmann I, Nowicki M, Blüher M. Autophagy in adipose tissue of patients with obesity and type 2 diabetes. Mol Cell Endocrinol. 2015; pii:S0303-7207(15)00146-X.

Knigge A, Klöting N, Schön MR, Dietrich A, Fasshauser M, Gärtner D, Lohmann T, Dreßler M, Stumvoll M, Kovacs P, Blüher M. ADCY5 gene expression in adipose tissue is related to obesity in men and mice. PLoS One. 2015;10:e0120742.

Lakowa N, Trieu N, Flehmig G, Lohmann T, Schön MR, Dietrich A, Zeplin PH, Langer S, Stumvoll M, Blüher M, Klöting N. Telomere length differences between subcutaneous and visceral adipose tissue in humans. Biochem Biophys Res Commun. 2015;457:426-32.

Kannt A, Pfenniger A, Teichert L, Tönjes A, Dietrich A, Schön MR, Klöting N, Blüher M. Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance. Diabetologia. 2015;58:799-808.

Lo JC, Ljubicic S, Leibiger B, Kern M, Leibiger IB, Moede T, Kelly ME, Chatterjee Bhowmick D, Murano I, Cohen P, Banks AS, Khandekar MJ, Dietrich A, Flier JS, Cinti S, Blüher M, Danial NN, Berggren PO, Spiegelman BM. Adipsin is an adipokine that improves β cell function in diabetes. Cell. 2014;158:41-53.

Derikx MH, Kovacs P, Scholz M, Masson E, Chen JM, Ruffert C, Lichtner P, Te Morsche RH, Cavestro GM, Algül H, Berg T, Bödeker H, Blüher M, Bruno MJ, Buch S, Bugert P, Cichoz-Lach H, Dabrowski A, Farré A, Frank J, Gasiorowska A, Geisz A, Goni E, Grothaus J, Grützmann R, Haas S, Hampe J, Hellerbrand C, Hegyi P, Huster D, Ioana M, Iodache S, Jurkowska G, Keim V, Landt O, Di Leo M, Lerch MM, Lévy P, Löhr MJ, Macek M, Malats N, Malecka-Panas E, Mariani A, Martorana D, Mayerle J, Mora J, Mössner J, Müller S, Ockenga J, Paderova J, Pedrazzoli S, Pereira SP, Pfützer R, Real FX, Rebours V, Ridinger M, Rietschel M, Rohde K, Sack S, Saftiou A, Schneider A, Schulz HU, Soyka M, Simon P, Skipworth J, Stickel F, Stumvoll M, Testoni PA, Tönjes A, Treiber M, Weiss FU, Werner J, Wodarz N, Férec C, Drenth JP, Witt H, Rosendahl J. Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study. Gut. 2014;64:1426-33.

Garnov N, Lindner N, Schaudinn A, Blüher M, Karlas T, Schütz T, Dietrich A, Kahn T, Busse H. Comparison of T1 relaxation times in aidpose tissue of severely obese patients and healthy lean subjects measured by 1.5 T MRI. NMR Biomed. 2014;27:1123-8.

Flehmig G, Scholz M, Klöting N, Fasshauer M, Tönjes A, Stumvoll M, Youn BS, Blüher M. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation.PLoS One. 2014;9:e99785.

Kern M, Kosacka J, Hesselbarth N, Brückner J, Heiker JT, Flehmig G, Klöting I, Kovacs P, Matz-Soja M, Gebhardt R, Krohn K, Sales S, Abshagen K, Shevchenko A, Stumvoll M, Blüher M, Klöting N. Liver-restricted Repin1 deficiency improves whole body insulin sensitivity, alters lipid metabolism and causes secondary changes in adipose tissue in mice. Diabetes. 2014;63:3295-309.

Cottilard A, Poitou C, Torcivia A, Bouillot JL, Dietrich A, Klöting N, Gregoire C, Lolmede K, Blüher M, Clement K. Adipocyte size treshold matters: link with risk of type 2 diabetes and improved insulin resistance after gastric bypass. J Clin Endocrinol Metab. 2014;99:E1477-70.

Haase J, Weyer U, Immig K, Klöting N, Blüher M, Eilers J,Bechmann I, Gericke M. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia. 2014;57:562-71.

Blüher M, Klöting N, Wueest S, Schoenle EJ, Schön MR, Dietrich A,Fasshauer M,Stumvoll M, Konrad D. Fas and FasL Expression in Human Adipose Tissue Is Related to Obesity, Insulin Resistance, and Type 2 Diabetes. J Clin Endocrinol Metab. 2014;99:E36-44.

Claussnitzer M, Dankel SN, Klocke B, Grallert H, Glunk V, Berulava T, Lee H, Oskolkov N, Fadista J, Ehlers K, Wahl S, Hoffmann C, Qian K, Rönn T, Riess H, Müller-Nurasyid M, Bretschneider N, Schroeder T, Skurk T, Horsthemke B; DIAGRAM+Consortium, Spieler D, Klingenspor M, Seifert M, Kern MJ, Mejhert N, Dahlman I, Hansson O, Hauck SM, Blüher M, Arner P, Groop L, Illig T, Suhre K, Hsu YH, Mellgren G, Hauner H, Laumen H. Leveraging cross-species transcription factor binding site patterns: from diabetes risk Loci to disease mechanisms.  Cell. 2014;156:343-58.

Schleinitz D, Klöting N, Lindgren CM, Breitfeld J, Dietrich A, Schön MR, Lohmann T, Dreßler M, Stumvoll M, McCarthy MI, Blüher M, Kovacs P. Fat depot-specific mRNA expression of novel loci associated with waist-hip ratio. Int J Obes (Lond). 2014;38:120-35.

Kovacs P, Miehle K, Sandner B, Stumvoll M, Blüher M. Insulin administration acutely decreases vaspin serum concentrations in humans.Obes Facts. 2013;6:86-8.

Sell H, Blüher M, Klöting N, Schlich R, Willems M, Ruppe F, Knoefel WT, Dietrich A, Fielding BA, Arner P, Frayn KN, Eckel J. Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro. Diabetes Care. 2013;36:4083-90.

Hoffmeister A, Tuennemann J, Sommerer I, Mössner J, Rittger A, Schleinitz D, Kratzsch J, Rosendahl J, Klöting N, Stahl T, Rossner S, Paroni F, Maedler K, Kovacs P, Blüher M. Genetic and biochemical evidence for a functional role of BACE1 in the regulation of insulin mRNA expression. Obesity (Silver Spring). 2013;21:E626-33.

Krist J, Wieder K,  Klöting N , Oberbach A, Kralisch S, Wiesner T, Schön MR, Gärtner D, Dietrich A, Shang E, Lohmann T, Dreßler M,  Fasshauer M ,  Stumvoll M , Blüher M. Effects of weight loss and exercise on apelin serum concentrations and adipose tissue expression in human obesity.  Obes Facts. 2013;6:57-69.

Heiker JT, Kern M, Kosacka J, Flehmig G, Stumvoll M, Shang E, Lohmann T, Dreßler M,  Kovacs P,  Blüher M, Klöting N. Nicotinamide nucleotide transhydrogenase mRNA expression is related to human obesity.  Obesity (Silver Spring). 2013;21:529-34.

Kosacka J, Nowicki M, Blüher M, Baum P, Stockinger M, Toyka KV, Klöting I, Stumvoll M, Serke H, Bechmann I, Klöting N. Increased autophagy in peripheral nerves may protect Wistar Ottawa Karlsburg W rats against neuropathy. Exp Neurol. 2013;250:125-35.

Blüher M, Rudich A, Klöting N, Golan R, Henkin Y, Rubin E, Schwarzfuchs D, Gepner Y, Stampfer MJ, Fiedler M, Thiery J, Stumvoll M, Shai I. Two patterns of adipokine and other biomarker dynamics in a long-term weight loss intervention. Diabetes Care. 2012; 35: 342-9.

Klöting N, Kovacs P, Kern M, Heiker JT, Breitfeld J, Kosacka J, Stumvoll M, Beck-SickingerAG, Blüher M. Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia. 2011;54:1819-23.

Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M, Stumvoll M, Blüher M. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010;299:E506-15.

Blüher M. Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes. 2009;117:241-50.

Youn BS, Bang SI, Klöting N, Park JW, Lee N, Oh JE, Pi KB, Lee TH, Ruschke K, Fasshauer M, Stumvoll M, Blüher M. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes. 2009;58:627-36.

Klöting N, Berthold S, Kovacs P, Schön MR, Fasshauer M, Ruschke K, Stumvoll M, Blüher M. MicroRNA expression in human omental and subcutaneous adipose tissue. PLoS One. 2009;4:e4699.

Klöting N, Graham TE, Berndt J, Kralisch S, Kovacs P, Wason CJ, Fasshauer M, Schön MR, Stumvoll M, Blüher M, Kahn BB. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab. 2007;6:79-87.

Gesta S, Blüher M, Yamamoto Y, Norris AW, Berndt J, Kralisch S, Boucher J, Lewis C, Kahn CR. Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci U S A. 2006;103:6676-81.


Sebastian Dommel, PhD student