The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.
Novel Adipose Tissue–Mediated Resistance to Diet-Induced Visceral Obesity in 11β-Hydroxysteroid Dehydrogenase Type 1–Deficient Mice
Open accessAbstract
The metabolic syndrome (visceral obesity, insulin resistance, type 2 diabetes, and dyslipidemia) resembles Cushing’s Syndrome, but without elevated circulating glucocorticoid levels. An emerging concept suggests that the aberrantly elevated levels of the intracellular glucocorticoid reamplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) found in adipose tissue of obese humans and rodents underlies the phenotypic similarities between idiopathic and “Cushingoid” obesity. Transgenic overexpression of 11β-HSD-1 in adipose tissue reproduces a metabolic syndrome in mice, whereas 11β-HSD-1 deficiency or inhibition has beneficial metabolic effects, at least on liver metabolism. Here we report novel protective effects of 11β-HSD-1 deficiency on adipose function, distribution, and gene expression in vivo in 11β-HSD-1 nullizygous (11β-HSD-1−/−) mice. 11β-HSD-1−/− mice expressed lower resistin and tumor necrosis factor-α, but higher peroxisome proliferator–activated receptor-γ, adiponectin, and uncoupling protein-2 mRNA levels in adipose, indicating insulin sensitization. Isolated 11β-HSD-1−/− adipocytes exhibited higher basal and insulin-stimulated glucose uptake. 11β-HSD-1−/− mice also exhibited reduced visceral fat accumulation upon high-fat feeding. High-fat–fed 11β-HSD-1−/− mice rederived onto the C57BL/6J strain resisted diabetes and weight gain despite consuming more calories. These data provide the first in vivo evidence that adipose 11β-HSD-1 deficiency beneficially alters adipose tissue distribution and function, complementing the reported effects of hepatic 11β-HSD-1 deficiency or inhibition.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“These include increased production of inflammatory cytokines, 35,36 plasminogen activator inhibitor-1, 37 and other bioactive products 38 -40 ; at the same time the potentially protective adipokine, adiponectin, is reduced.41,42”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
The hormone resistin links obesity to diabetes
Steppan, C. M., Bailey, S. T., Bhat, S., Brown, E. J., Banerjee, R. R., Wright, C. M., Patel, H. R., Ahima, R. S., & Lazar, M. A. (2001) · Nature · doi:10.1038/35053000 · Cited by 4,755
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
Kliewer, S. A., Sundseth, S. S., Jones, S. A., Brown, P. J., Wisely, G. B., Koble, C. S., Devchand, P., Wahli, W., Willson, T. M., Lenhard, J. M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4318 · Cited by 2,164
Relation of Body Fat Distribution to Metabolic Complications of Obesity*
KISSEBAH, A. H., VYDELINGUM, N., MURRAY, R., EVANS, D. J., KALKHOFF, R. K., & ADAMS, P. W. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-2-254 · Cited by 1,909
A transgenic model of visceral obesity and the metabolic syndrome
Masuzaki, H., Paterson, J., Shinyama, H., Morton, N. M., Mullins, J. J., Seckl, J. R., & Flier, J. S. (2001) · Science · doi:10.1126/science.1066285 · Cited by 1,766
Self-citationTowards a molecular understanding of adaptive thermogenesis
Lowell, B. B., & Spiegelman, B. M. (2000) · Nature · doi:10.1038/35007527 · Cited by 1,630
Adipogenesis and Obesity: Rounding Out the Big Picture
Spiegelman, B. M., & Flier, J. S. (1996) · Cell · doi:10.1016/s0092-8674(00)81359-8 · Cited by 1,262
Self-citation
Cited by
Sorted by citations
Items 101–200 of 546
Chronic social stress, hedonism and vulnerability to obesity: Lessons from Rodents
Coccurello, R., D'Amato, F. R., & Moles, A. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.05.018 · Cited by 83
Justesen, J., Mosekilde, L., Holmes, M. C., Stenderup, K., Gasser, J. A., Mullins, J. J., Seckl, J. R., & Kassem, M. S. (2004) · Endocrinology · doi:10.1210/en.2003-1427 · Cited by 78
Self-citationDrake, A. J., Livingstone, D. E. W., Andrew, R., Seckl, J. R., Morton, N. M., & Walker, B. R. (2004) · Endocrinology · doi:10.1210/en.2004-1063 · Cited by 77
“on exposure to a high-fat (HF) diet (15).”
BackgroundSelf-citationComparative enzymology of 11β-hydroxysteroid dehydrogenase type 1 from six species
Arampatzis, S., Kadereit, B., Schuster, D., Balázs, Z., Schweizer, R. A. S., Frey, F. J., Langer, T., & Odermatt, A. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01736 · Cited by 75
“In contrast, mice with targeted disruption of 11 -HSD1 show, upon starvation, attenuated activation of key hepatic gluconeogenic enzymes and are resistant to hyperglycemia provoked by obesity or stress (Kotelevtsev et al. 1997, Morton et al. 2004).”
BackgroundGambineri, A., Vicennati, V., Genghini, S., Tomassoni, F., Pagotto, U., Pasquali, R., & Walker, B. R. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2222 · Cited by 75
“11 -HSD1 seems to be important in metabolic disease, because in mice, increasing enzyme activity in adipose tissue enhances local glucocorticoid levels and produces a metabolic syndrome (3), whereas decreasing enzyme activity protects against obesity and the metabolic syndrome (4, 5).”
BackgroundSelf-citation11β-hydroxysteroid dehydrogenase type 1 inhibitors: a review of recent patents
Boyle, C. D., & Kowalski, T. J. (2009) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770902967658 · Cited by 74
“Transgenic overexpression of 11β-HSD1 in adipose tissue of mice produces intra-abdominal obesity, insulin resistance, dyslipidemia and hypertension [32-34] in the absence of elevated corticosterone, whereas mice with targeted disruption of the 11β-HSD1 gene are resistant to diet-induced obesity [35], and display impro…”
Adiposopathy: why do adiposity and obesity cause metabolic disease?
Bays, H. E., & Ballantyne, C. M. (2006) · Future Lipidology · doi:10.2217/17460875.1.4.389 · Cited by 75
Chapman, K. E., Coutinho, A. E., Gray, M., Gilmour, J. S., Savill, J., & Seckl, J. R. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1366.030 · Cited by 73
Self-citationNuotio-Antar, A. M., Hachey, D. L., & Hasty, A. H. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00522.2007 · Cited by 73
“Conversely, global 11 -HSD1 deficiency in mice fed a highfat diet is associated with decreased weight gain and improved serum HDL lipoprotein profiles, despite increased adrenocortex-derived circulating glucocorticoids (24, 34, 35).”
Background11 β ‐Hydroxysteroid dehydrogenase type 1 inhibition in type 2 diabetes mellitus
Hollis, G. F., & Huber, R. (2010) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2010.01305.x · Cited by 72
11β-hydroxysteroid dehydrogenases: A growing multi-tasking family
Gómez-Sánchez, E. P., & Gómez-Sánchez, C. E. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111210 · Cited by 72
Alberti, L., Girola, A., Gilardini, L., Conti, A., Cattaldo, S., Micheletto, G., & Invitti, C. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803677 · Cited by 69
Baudrand, R. F., Carvajal, C. A., Riquelme, A. J., Morales, M., Solı́s, N., Pizarro, M., Escalona, A., Boza, C., Pérez, G., Domínguez, A., et al. (2009) · Obesity Surgery · doi:10.1007/s11695-009-9937-0 · Cited by 68
“Conversely, 11betaHSD1-knockout mice are protected from both [18].”
BackgroundLavery, G. G., Zielinska, A. E., Gathercole, L., Hughes, B. A., Semjonous, N. M., Guest, P., Saqib, K. M., Sherlock, M., Reynolds, G. M., Morgan, S., et al. (2012) · Endocrinology · doi:10.1210/en.2012-1019 · Cited by 69
Neuroendocrine and metabolic effects of adipocyte-derived hormones
Jackson, M. B., & Ahima, R. S. (2006) · Clinical Science · doi:10.1042/cs20050243 · Cited by 68
Carter, R. N., Paterson, J. M., Tworowska, U., Stenvers, D. J., Mullins, J. J., Seckl, J. R., & Holmes, M. C. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01899.x · Cited by 68
Self-citationWan, Z., Chenail, E., Xiang, J. S., Li, H., Ipek, M., Bard, J., Svenson, K., Mansour, T. S., Xu, X., Tian, X., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900639u · Cited by 66
Mueller, K. M., Hartmann, K., Kaltenecker, D., Vettorazzi, S., Bauer, M., Mauser, L., Amann, S., Jall, S., Fischer, K., Esterbauer, H., et al. (2016) · Diabetes · doi:10.2337/db16-0381 · Cited by 67
“In mice and humans, an increase in GC regeneration by the enzyme 11β-HSD1 within WAT compartments suggests a role of the GC-GR axis in common obesity (2; 12-16).”
BackgroundMorton, N. M., Densmore, V. S., Wamil, M., Ramage, L. E., Nichol, K., Bünger, L., Seckl, J. R., & Kenyon, C. J. (2005) · Diabetes · doi:10.2337/diabetes.54.12.3371 · Cited by 66
“Weight gain in Fat mice on the high-fat diet was associated with a 34% (body weight adjusted) increase in subcutaneous fat mass but a 25% reduction in mesenteric adipose fat mass with high-fat feeding (Table 4), a pattern of preferential fat deposition similar to 11 -HSD-1–deficient mice (20).”
BackgroundMethodInfluentialSelf-citationHu, G., Lin, H., Lian, Q., Zhou, S., Guo, J., Zhou, H.-Y., Chu, Y., & Ge, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0049976 · Cited by 64
“In addition, Hsd11b1 null mice were resistant to HFD-induced insulin resistance, obesity and dyslipidaemia [25].”
BackgroundAdamantane sulfone and sulfonamide 11-β-HSD1 Inhibitors
Sorensen, B. K., Winn, M., Rohde, J., Shuai, Q., Wang, J., Fung, S., Monzon, K., Chiou, W. J. H., Stolarik, D. F., Imade, H. M., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.10.008 · Cited by 64
Nixon, M., Wake, D. J., Livingstone, D. E. W., Stimson, R. H., Esteves, C. L., Seckl, J. R., Chapman, K. E., Andrew, R., & Walker, B. R. (2012) · Diabetes · doi:10.2337/db11-0931 · Cited by 64
“Protective metabolic effects of 11b-HSD1 deficiency in mice receiving a high-fat diet have been described previously (22) and are shown here to bear remarkable similarity to the pattern of effects of salicylates on glucose tolerance and adipose lipase expression.”
BackgroundSelf-citationIdentification of 11β-HSD1 inhibitors through enhanced sampling methods
Singh, R., Bhardwaj, V. K., Das, P., & Purohit, R. (2022) · Chemical Communications · doi:10.1039/d1cc06894f · Cited by 63
Cortisol dysregulation in obesity-related metabolic disorders
Baudrand, R. F., & Vaidya, A. (2015) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000152 · Cited by 64
“The opposite effects were seen in 11b-HSD1 adipose tissue knockout mice – when challenged with hypercaloric diets – these knockout animals had reduced visceral fat mass and did not develop diabetes [34].”
BackgroundThermogenic and metabolic antiobesity drugs: rationale and opportunities
Clapham, J. C., & Arch, J. R. S. (2007) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00608.x · Cited by 60
Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter?
Magueresse‐Battistoni, B. L. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17249403 · Cited by 64
Anuka, E., Gal, M., Stocco, D. M., & Orly, J. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.02.003 · Cited by 60
Franks, P. W., Knowler, W. C., Nair, S., Koška, J., Lee, Y., Lindsay, R. S., Walker, B. R., Looker, H. C., Permana, P. A., Tataranni, P. A., et al. (2004) · Hypertension · doi:10.1161/01.hyp.0000144294.28985.d5 · Cited by 59
Self-citationBerthiaume, M., Laplante, M., Festuccia, W. T., Cianflone, K., Turcotte, L. P., Joanisse, D. R., Olivecrona, G., Thieringer, R., & Deshaies, Y. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00276.2007 · Cited by 58
Wamil, M., Battle, J. H., Turban, S., Kipari, T. M. J., Seguret, D., Peixoto, R. D. S., Nelson, Y. B., Nowakowska, D., Ferenbach, D. A., Ramage, L. E., et al. (2011) · Diabetes · doi:10.2337/db10-0830 · Cited by 57
Self-citationAshraf, S. A., Elkhalifa, A. E. O., Mehmood, K., Adnan, M., Khan, M. A., Eltoum, N. E., Krishnan, A., & Baig, M. S. (2021) · Molecules · doi:10.3390/molecules26195957 · Cited by 62
Insulin and Dexamethasone Dynamically Regulate Adipocyte 11β-Hydroxysteroid Dehydrogenase Type 1
Balachandran, A., Guan, H., Sellan, M. E., Uum, S. H. M. V., & Yang, K. (2008) · Endocrinology · doi:10.1210/en.2008-0088 · Cited by 57
Adipocyte glucocorticoid receptor has a minor contribution in adipose tissue growth
Desarzens, S., & Faresse, N. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0121 · Cited by 55
Toneatto, J., Guber, S., Charó, N. L., Susperreguy, S., Schwartz, J., Galigniana, M. D., & Piwien‐Pilipuk, G. (2013) · Journal of Cell Science · doi:10.1242/jcs.125799 · Cited by 55
“In contrast, glucocorticoid inactivation is associated with resistance to metabolic dysfunction (Kershaw et al., 2005; Morton et al., 2004).”
BackgroundRecent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases
Martocchia, A., Stefanelli, M., Falaschi, G. M., Toussan, L., Ferri, C., & Falaschi, P. (2015) · Aging Clinical and Experimental Research · doi:10.1007/s40520-015-0353-0 · Cited by 54
Walker, B. R. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s002966510700523x · Cited by 52
“Intriguingly, high-fat feeding of mice (Morton et al. 2004b) or rats (Drake et al. 2005) results in down-regulation of 11b-HSD1 selectively within the adipose tissue.”
BackgroundInfluentialSelf-citationGu, X., Dragovic, J., Koo, G. C., Koprak, S., LeGrand, C. B., Mundt, S. S., Shah, K., Springer, M. S., Tan, E. Y., Thieringer, R., et al. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.08.052 · Cited by 54
Hintzpeter, J., Stapelfeld, C., Loerz, C., Martin, H.-J., & Maser, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084468 · Cited by 53
“11b-HSD1-deficient mice show enhanced glucose tolerance, improved hepatic insulin resistance, attenuated gluconeogenesis, and an improved lipid and lipoprotein profile [32–34].”
BackgroundWang, S. J. Y., Birtles, S., de Schoolmeester, J., Swales, J. G., Moody, G., Hislop, D. C., O’Dowd, J. F., Smith, D. M., Turnbull, A. V., & Arch, J. R. S. (2006) · Diabetologia · doi:10.1007/s00125-006-0239-y · Cited by 53
Ignatova, I. D., Kostadinova, R. M., Goldring, C. E., Nawrocki, A. R., Frey, F. J., & Frey, B. M. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90531.2008 · Cited by 53
11β-Hydroxysteroid dehydrogenase 1: Regeneration of active glucocorticoids is only part of the story
Odermatt, A., & Klusoňová, P. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.08.011 · Cited by 53
Taves, M. D., Otsuka, S., Taylor, M. A., Donahue, K. M., Meyer, T. J., Cam, M. C., & Ashwell, J. D. (2023) · Journal of Clinical Investigation · doi:10.1172/jci164599 · Cited by 52
Ishii, T., Masuzaki, H., Tanaka, T., Arai, N., Yasue, S., Kobayashi, N., Tomita, T., Noguchi, M., Fujikura, J., Ebihara, K., et al. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.11.032 · Cited by 51
Self-citationGögebakan, Ö., Andres, J., Biedasek, K., Mai, K., Kühnen, P., Krude, H., Isken, F., Rudovich, N. N., Osterhoff, M. A., Kintscher, U., et al. (2011) · Diabetes · doi:10.2337/db10-0902 · Cited by 49
“Very similar to GIPR KO mice, 11b-HSD1 gene knockout mice exhibited improved glucose tolerance, reduced weight gain, and reduced fat accumulation in visceral fat depots under a high-fat diet (15).”
BackgroundBerthiaume, M., Sell, H., Lalonde, J., Gélinas, Y., Tchernof, A., Richard, D., & Deshaies, Y. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00339.2004 · Cited by 51
Wang, Y.-J., Huang, S., Feng, Y., Ning, M., & Leng, Y. (2012) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.87 · Cited by 50
Jean, D. J. S., Yuan, C., Bercot, E. A., Cupples, R. L., Chen, M., Fretland, J., Hale, C., Hungate, R. W., Komorowski, R., Véniant, M. M., et al. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm061214f · Cited by 50
Campbell, J. E., Fediuc, S., Hawke, T. J., & Riddell, M. C. (2009) · Metabolism · doi:10.1016/j.metabol.2009.01.002 · Cited by 49
“Indeed, reducing GC exposure in adipose tissue protects from dietinduced obesity in rodents [14,15].”
BackgroundResultDysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond
Konstantakou, P., Mastorakos, G. P., Vrachnis, N., Tomlinson, J., & Valsamakis, G. (2016) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2016.1171308 · Cited by 49
Boscaro, M., Giacchetti, G., & Ronconi, V. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06597.x · Cited by 49
Fructose consumption enhances glucocorticoid action in rat visceral adipose tissue
Bursać, B. N., Djordjevic, A. D., Teofilović, A., Milutinović, D. V., Veličković, N. A., Nestorović, N. M., & Matić, G. M. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2012.09.002 · Cited by 47
11β-Hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of type 2 diabetes
Morgan, S., & Tomlinson, J. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.504713 · Cited by 47
“Hepatic gluconeogenesis is attenuated in the fasted state [32], and basal and insulin-stimulated glucose uptake is increased in adipose tissue [33].”
Gambineri, A., Tomassoni, F., Munarini, A., Stimson, R. H., Mioni, R., Pagotto, U., Chapman, K. E., Andrew, R., Mantovani, V., Pasquali, R., et al. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0091 · Cited by 49
Self-citationGlucocorticoid Effects on Adiponectin Expression
Sukumaran, S., DuBois, D. C., Jusko, W. J., & Almon, R. R. (2012) · Vitamins and hormones · doi:10.1016/b978-0-12-398313-8.00007-5 · Cited by 46
“Morton et al. showed that tissue-specific knockout of 11bHSD1 in adipose tissue in mice results in increased adiponectin gene expression (Morton et al., 2004).”
Densmore, V. S., Morton, N. M., Mullins, J. J., & Seckl, J. R. (2006) · Endocrinology · doi:10.1210/en.2006-0106 · Cited by 47
“Plasma leptin, which at high levels can overcome glucocorticoid up-regulation of AGRP (54), varied similarly in the two genotypes and, therefore, is unlikely to be involved, but insulin levels were lower in HF-fed 11 HSD1 / mice, as previously reported (18).”
InfluentialSelf-citationSawada, T., & Nakada, M. (2013) · Organic Letters · doi:10.1021/ol303459x · Cited by 46
Paterson, J. M., Holmes, M. C., Kenyon, C. J., Carter, R., Mullins, J. J., & Seckl, J. R. (2006) · Endocrinology · doi:10.1210/en.2006-0603 · Cited by 46
“C57BL/6J congenic 11βHSD1-/- mice (14) were intercrossed with ApoE-HSD1 mice (line 1065) at F3 C57BL/6J backcross (17) to generate four genotype-defined study groups of age-matched littermates; control nontransgenic (nonTG), ApoE-HSD1 transgenic (TG), 11β-HSD1-/-, and 11β-HSD1-/-/ApoEHSD1 (11βHSD1-/- xTG) mice with tr…”
MethodSelf-citationWamil, M., Andrew, R., Chapman, K. E., Street, J. M., Morton, N. M., & Seckl, J. R. (2008) · Endocrinology · doi:10.1210/en.2008-0420 · Cited by 46
“11 -HSD1 / mice have a cardioprotective lipid profile (low low-density lipoprotein, high HDL) (8), and pharmacological inhibition of 11 -HSD1 activity is atheroprotective (10).”
BackgroundInfluentialSelf-citationMakkonen, J., Westerbacka, J., Kolak, M., Sutinen, J., Cornér, A., Hamsten, A., Fisher, R. M., & Yki‐Järvinen, H. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803635 · Cited by 45
Peixoto, R. D. S., Turban, S., Battle, J. H., Chapman, K. E., Seckl, J. R., & Morton, N. M. (2008) · Endocrinology · doi:10.1210/en.2007-1028 · Cited by 45
“that 11-HSD1 contributes to altered regional fat accumulation in mature adipocytes (9, 12 ).”
BackgroundMethodResultInfluentialSelf-citation米本崇子, Masuzaki, H., Yasue, S., Okada, S., Kozuka, C., Tanaka, T., Noguchi, M., Tomita, T., Fujikura, J., Yamamoto, Y., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00320.2009 · Cited by 44
Self-citationStress, glucocorticoid signaling pathway, and metabolic disorders
de Guia, R. M. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.06.038 · Cited by 43
Thieringer, R., & Hermanowski‐Vosatka, A. (2005) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.3.5.911 · Cited by 43
Zhao, J., Cowley, M. J., Lee, P., Birzniece, V., Kaplan, W. H., & Ho, K. K. Y. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2679 · Cited by 43
“Conversely, adipose-specific HSD11 1 knockout mice exhibit reduced visceral fat (33).”
BackgroundKipari, T. M. J., Hadoke, P. W. F., Iqbal, J., Man, T., Miller, E., Coutinho, A. E., Zhang, Z., Sullivan, K. M., Mitić, T., Livingstone, D. E. W., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-219105 · Cited by 42
“This may reflect the already markedly hyperlipidemic state of this strain and/or the only marginally obesogenic effect of WD—the beneficial effects of 11 -HSD1 deficiency/inhibition on cardiovascular risk factors predominantly occur in obesity (16, 17).”
Self-citationFat-brain connections: Adipocyte glucocorticoid control of stress and metabolism
de Kloet, A. D., & Herman, J. P. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.10.005 · Cited by 46
Sundbom, M., Kaiser, C., Björkstrand, E., Castro, V. M., Larsson, C., Selén, G., Nyhem, C. S., & James, S. R. (2008) · BMC Pharmacology · doi:10.1186/1471-2210-8-3 · Cited by 43
Park, J. S., Rhee, S. D., Kang, N. S., Jung, W. H., Kim, H. Y., Kim, J. H., Kang, S. K., Cheon, H. G., Ahn, J. H., & Kim, K. Y. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.01.020 · Cited by 41
“020 knock mice showed a reduction in high-fat diet-induced obesity with improved insulin sensitivity and lipid profiles [2].”
BackgroundBaudrand, R. F., Campino, C., Carvajal, C. A., Olivieri, O., Guidi, G. C., Faccini, G., Sateler, J., Cornejo, J., Martín, B. S., Domínguez, J. M., et al. (2011) · Steroids · doi:10.1016/j.steroids.2011.09.010 · Cited by 44
Hepatic 11beta‐HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis
Kotsias-Konopelska, S., Kienitz, T., Hughes, B. A., Pirlich, M., Bauditz, J., Lochs, H. H., Strasburger, C. J., Stewart, P. M., & Quinkler, M. O. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03358.x · Cited by 40
Nakano, S., Inada, Y., Masuzaki, H., Tanaka, T., Yasue, S., Ishii, T., Arai, N., Ebihara, K., Hosoda, K., Maruyama, K., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00340.2006 · Cited by 41
“On the other hand, 11β-HSD1 knockout mice (32) as well as adipose-specific 11β-HSD2 overexpressors which mimicked adipose-specific 11β-HSD1 knockout mice (18) are protected against the metabolic Page 5 of 43”
BackgroundSelf-citationLi, G., Hernández‐Ono, A., Crooke, R. M., Graham, M. J., & Ginsberg, H. N. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m013748 · Cited by 41
Papargyri, P., Zapanti, E. D., Salakos, N., Papargyris, L., Bargiota, Α., & Mastorakos, G. P. (2018) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2018.1543585 · Cited by 42
Glucocorticoids and Brown Adipose Tissue: Do glucocorticoids really inhibit thermogenesis?
Luijten, I. H. N., Cannon, B., & Nedergaard, J. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.07.002 · Cited by 44
The discovery of 2-anilinothiazolones as 11β-HSD1 inhibitors
Yuan, C., Jean, D. J. S., Liu, Q., Cai, L., Li, A., Han, N., Moniz, G. A., Askew, B. C., Hungate, R. W., Johansson, L., et al. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.09.070 · Cited by 41
Wang, L., Liu, J., Zhang, A., Cheng, P., Zhang, X., Lv, S., Wu, L., Yu, J., Di, W., Zha, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040056 · Cited by 43
“In contrast, mice with a targeted disruption of the 11b-HSD1 gene (11b-HSD-1 mice) exhibited enhanced glucose tolerance, attenuated gluconeogenic responses, and improved lipid profile [12,13,14].”
BackgroundGenetic manipulation of 11β-hydroxysteroid dehydrogenases in mice
Paterson, J. M., Seckl, J. R., & Mullins, J. J. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00017.2005 · Cited by 40
“However, reduced weight gain may be accounted for in part by the fact that the 11 -HSD1 null mutants have a higher body temperature and therefore presumably increased energy expenditure (55).”
BackgroundInfluentialSelf-citation11β-HSD as a New Target in Pharmacotherapy of Metabolic Diseases
Kupczyk, D., Bilski, R., Kozakiewicz, M., Studzińska, R., Kędziora–Kornatowska, K., Kosmalski, T., Pedrycz, A., & Głowacka, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23168984 · Cited by 42
Gibbs, J. P., Emery, M. G., McCaffery, I., Smith, B., Gibbs, M. A., Akrami, A., Rossi, J. M., Paweletz, K. L., Gastonguay, M. R., Bautista, E., et al. (2010) · The Journal of Clinical Pharmacology · doi:10.1177/0091270010374470 · Cited by 40
Blum, A., Loerz, C., Martin, H., Staab-Weijnitz, C. A., & Maser, E. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.09.003 · Cited by 40
Xu, Z., Tice, C. M., Zhao, W. L., Cacatian, S. T., Ye, Y.-J., Singh, S. B., Lindblom, P., McKeever, B. M., Krosky, P. M., Kruk, B. A., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm2005354 · Cited by 40
Peripheral targets in obesity treatment: a comprehensive update
Chatzigeorgiou, A., Kandaraki, E., Papavassiliou, A. G., & Koutsilieris, M. (2014) · Obesity Reviews · doi:10.1111/obr.12163 · Cited by 44
Lloyd, D. J., Helmering, J., Cordover, D. H., Bowsman, M., Chen, M., Hale, C., Fordstrom, P., Zhou, M., Wang, M., Kaufman, S. A., et al. (2009) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2009.01034.x · Cited by 40
Discovery of cyclicsulfonamide derivatives as 11β-hydroxysteroid dehydrogenase 1 inhibitors
Kim, S. H., Ramu, R., Kwon, S. W., Lee, S.-H., Kim, C. H., Kang, S. K., Rhee, S. D., Bae, M. A., Ahn, S. H., Ha, D. C., et al. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.12.035 · Cited by 39
Stomby, A., Šimonytė, K., Mellberg, C., Ryberg, M., Stimson, R. H., Larsson, C. L., Lindahl, B., Andrew, R., Walker, B. R., & Olsson, T. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.188 · Cited by 42
Self-citationBaudrand, R. F., Domínguez, J. M., Carvajal, C. A., Riquelme, A. J., Campino, C., Macchiavello, S. P., Božinović, M., Morales, M., Pizarro, M., Solı́s, N., et al. (2011) · Metabolism · doi:10.1016/j.metabol.2011.05.001 · Cited by 38
“Previous reports have found a good correlation between 11β-HSD1 mRNA and protein levels in adipose tissue [27].”
BackgroundInfluential11β-HSD1, Inflammation, Metabolic Disease and Age-related Cognitive (dys)Function
Chapman, K. E., & Seckl, J. R. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9504-9 · Cited by 37
“despite normal or modestly elevated plasma corticosterone levels, 11b-HSD1-deficient mice are insulin sensitised, resist hyperglycaemia with stress or high fat diet and show attenuated induction of gluconeogenic enzymes upon fasting [111, 113].”
BackgroundSelf-citationHarno, E., Cottrell, E. C., Keevil, B. G., deSchoolmeester, J., Bohlooly‐Y, M., Andersén, H., Turnbull, A. V., Leighton, B., & White, A. E. (2013) · Endocrinology · doi:10.1210/en.2013-1362 · Cited by 38
Do, T. T. H., Garcia, M., Dalle, H., Dorothée, G., Moldes, M., Fève, B., & Buyse, M. (2018) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2018.08.010 · Cited by 36
Sun, D., Wang, Z., Di, Y., Jaén, J. C., Labelle, M., Ma, J., Miao, S., Sudom, A. M., Tang, L. V., Tomooka, C. S., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.05.025 · Cited by 38
Perinatal programming of metabolic diseases: The role of glucocorticoids
Facchi, J. C., de Lima, T. A. L., de Oliveira, L. R., Costermani, H. D. O., Miranda, G. D. S., & de Oliveira, J. C. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154047 · Cited by 38
Andersson, T., Šimonytė, K., Andrew, R., Strand, M., Burén, J., Walker, B. R., Mattsson, C., & Olsson, T. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008475 · Cited by 37
“11bHSD1 knockout mice are protected from visceral fat accumulation when fed a high-fat diet [10], while selective over-expression of 11bHSD1 in adipose tissue results in abdominal obesity, insulin resistance, and hypertension [11,12].”
BackgroundSelf-citationBrief review: Glucocorticoid excretion in obesity
Müssig, K., Remer, T., & Maser-Gluth, C. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.01.008 · Cited by 36
Crystal Structures of 11β-Hydroxysteroid Dehydrogenase Type 1 and Their Use in Drug Discovery
THOMAS, M. P., & Potter, B. V. L. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.10.282 · Cited by 36
Zhang, Y., Zhong, X., Gjoka, Z., Li, Y., Stochaj, W. R., Stahl, M., Kriz, R., Tobin, J. F., Erbe, D. V., & Suri, V. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.12.004 · Cited by 37
Adipose tissue in cortisol excess: What Cushing’s syndrome can teach us?
Bavaresco, A., Mazzeo, P., Lazzara, M., & Barbot, M. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116137 · Cited by 41
Synthesis of Potent and Orally Efficacious 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor HSD-016
Wan, Z., Chenail, E., Li, H., Kendall, C., Youchu, W., Gingras, S., Xiang, J. S., Massefski, W. W., Tarek, S. M., & Saiah, E. (2011) · The Journal of Organic Chemistry · doi:10.1021/jo200958a · Cited by 35
Constantinopoulos, P., Michalaki, M. A., Kottorou, A. E., Habeos, I. G., Psyrogiannis, A. I., Kalfarentzos, F., & Kyriazopoulou, V. E. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0626 · Cited by 35
Praveenkumar, E., Gurrapu, N., Kolluri, P. K., Yerragunta, V., Kunduru, B. R., & Subhashini, N. J. P. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.103056 · Cited by 35
Pérez-Echarri, N., Pérez‐Matute, P., Martínez, J. A., Martí, A., & Moreno-Aliaga, M. J. (2005) · Journal of Physiology and Biochemistry · doi:10.1007/bf03167050 · Cited by 35
Metadata
- Authors
- Morton, N. M., Paterson, J. M., Masuzaki, H., Holmes, M. C., Staels, B., Fievet, C., Walker, B. R., Flier, J. S., Mullins, J. J., & Seckl, J. R.
- Affiliations
- Western General Hospital (GB)
- University of Edinburgh (GB)
- Kyoto University (JP)
- Inserm (FR)
- Département d’ Athérosclérose,U.545 INSERM, Institut Pasteur de Lille, Lille, France
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-04-01
- Volume
- 53
- Issue
- 4
- Pages
- 931-938
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2154972651
- Cited by
- 512
- References
- 49
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 9 · 2021: 9 · 2020: 5 · 2019: 10 · 2018: 10 · 2017: 12 · 2016: 21 · 2015: 19 · 2014: 24 · 2013: 35 · 2012: 37
- FWCI
- 32.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- 11β-hydroxysteroid dehydrogenase type 1, visceral obesity, adipose tissue, metabolic syndrome, insulin resistance, resistin, TNF-α, PPARγ, adiponectin, UCP2, insulin-stimulated glucose uptake, high-fat diet, body fat distribution, type 2 diabetes
- MeSH terms
- Uncoupling Protein 2, Adipose Tissue, Animals, Blood Glucose, Body Temperature, Body Weight, Cholesterol, Diet, Gene Expression Regulation, Glucose Tolerance Test, Insulin, Ion Channels, Male, Obesity, Transcription Factors, Triglycerides, Adipocytes, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Mitochondrial Proteins, Membrane Transport Proteins, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
