The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
Abstract
Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Increases in adiponectin have been demonstrated to improve insulin sensitivity through insulin-sensitizing effects in mice.
“Increases in adiponectin have been demonstrated to improve insulin sensitivity through insulin-sensitizing effects in mice [20].”
From Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1). (2023) · cites this paper as [20]
Adiponectin is exclusively produced in adipocytes, and adiponectin levels are lower in type 2 diabetes and obesity compared to the healthy state.
“Adiponectin is exclusively produced in adipocytes, and adiponectin levels are lower in T2D and obesity compared to the healthy state [20, 21].”
From Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1). (2023) · cites this paper as [20]
In rodents, injection of recombinant adiponectin increases fat oxidation, reduces intramyocellular lipid, and improves insulin sensitivity.
“(v) in rodents, injection of recombinant adiponectin increases fat oxidation, reduces intamyocellular lipid, and improves insulin sensitivity [77];”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [77]
High-fat diet-induced obesity leads to reduced expression of ApN, thereby causing insulin resistance.
“High-fat diet-induced obesity leads to reduced expression of ApN, thereby causing insulin resistance [47].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [47]
Administration of ApN lowered blood sugar and reduced insulin resistance in mice under a high-fat diet.
“Administration of ApN lowered blood sugar and reduced insulin resistance in mice under a high-fat diet (HFD) [47].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [47]
Adiponectin administration decreases IHTG, increases hepatic insulin sensitivity, and reverses obesity-related skeletal muscle insulin resistance.
“Adiponectin administration decreases IHTG (35), increases hepatic insulin sensitivity (36), and reverses obesity-related skeletal muscle insulin resistance (37).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [37]
It is thought that adiponectin can decrease the insulin resistance of obesity.
“It is thought that adiponectin can decrease the insulin resistance of obesity (28–30).”
From Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults (2004) · cites this paper as [30]
In one animal model, leptin alone produced a near-maximal effect, whereas a second model demonstrated a synergistic effect with adiponectin.
“Likewise, in one animal model, leptin alone produced a near-maximal effect (35), whereas a second model demonstrated a synergistic effect with adiponectin (33).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [33]
Adiponectin is another adipokine that is associated with increased insulin sensitivity and fatty acid oxidation.
“Adiponectin is another adipokine that is associated with increased insulin sensitivity and fatty acid oxidation (33).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [33]
Cites
Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity
Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J.-I., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0255 · Cited by 4,856 · see citing works
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 · see citing works
A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes
Scherer, P. E., Williams, S. P., Fogliano, M., Baldini, G., & Lodish, H. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26746 · Cited by 3,238 · see citing works
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity
Hu, E., Liang, P., & Spiegelman, B. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.18.10697 · Cited by 2,239 · see citing works
Maeda, K., Okubo, K., Shimomura, I., Funahashi, T., Matsuzawa, Y., & Matsubara, K. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0587 · Cited by 2,081 · see citing works
Fruebis, J., Tsao, T., Javorschi, S., Ebbets-Reed, D., Erickson, M., Yen, F. T., Bihain, B. E., & Lodish, H. F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.2005 · Cited by 1,987 · see citing works
Roles of PPARs in health and disease
Kersten, S., Desvergne, B., & Wahli, W. (2000) · Nature · doi:10.1038/35013000 · Cited by 1,956 · see citing works
PPARγ Promotes Monocyte/Macrophage Differentiation and Uptake of Oxidized LDL
Tontonoz, P., Nagy, L., Alvarez, J. G. A., Thomázy, V. A., & Evans, R. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81575-5 · Cited by 1,800 · see citing works
Ouchi, N., Kihara, S., Arita, Y., Okamoto, Y., Maeda, K., Kuriyama, H., Hotta, K., Nishida, M., Takahashi, M., Muraguchi, M., et al. (2000) · Circulation · doi:10.1161/01.cir.102.11.1296 · Cited by 1,730 · see citing works
Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting
Kersten, S., Seydoux, J., Peters, J. M., Gonzalez, F. J., Desvergne, B., & Wahli, W. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6223 · Cited by 1,649 · see citing works
Towards a molecular understanding of adaptive thermogenesis
Lowell, B. B., & Spiegelman, B. M. (2000) · Nature · doi:10.1038/35007527 · Cited by 1,630 · see citing works
PPARγ Mediates High-Fat Diet–Induced Adipocyte Hypertrophy and Insulin Resistance
Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Komeda, K., Satoh, S., Nakano, R., Ishii, C., 杉山, 拓., et al. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80210-5 · Cited by 1,342 · see citing works
Self-citationAdipogenesis 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 1,254 · see citing works
Schoonjans, K., Peinado‐Onsurbe, J., Lefebvre, A. M., Heyman, R. A., Briggs, M., Deeb, S., Staels, B., & Auwerx, J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00918.x · Cited by 1,173 · see citing works
Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S., & Goldstein, J. L. (1999) · Nature · doi:10.1038/43448 · Cited by 1,038 · see citing works
Isolation and Characterization of GBP28, a Novel Gelatin-Binding Protein Purified from Human Plasma
Nakano, Y., Tobe, T., Choi-Miura, N.-H., Mazda, T., & Tomita, M. (1996) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a021483 · Cited by 915 · see citing works
Self-citationEnhanced expression of PAI–1 in visceral fat: Possible contributor to vascular disease in obeisty
Shimomura, I., Funahasm, T., Takahashi, M., Maeda, K., Kotani, K., Nakamura, T., Yamashita, S., Miura, M., Fukuda, Y., Takemura, K., et al. (1996) · Nature Medicine · doi:10.1038/nm0796-800 · Cited by 890 · see citing works
The role of TNFα and TNF receptors in obesity and insulin resistance
Hotamisligil, G. S. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00490.x · Cited by 780 · see citing works
Friedman, J. M. (2000) · Nature · doi:10.1038/35007504 · Cited by 701 · see citing works
Vionnet, N., Hani, E. H., Dupont, S., Gallina, S., Francke, S., Dotte, S., de Matos, F., Durand, E., Leprêtre, F., Lecœur, C., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/316887 · Cited by 679 · see citing works
Self-citationSurgical implantation of adipose tissue reverses diabetes in lipoatrophic mice
Gavrilova, O., Marcus-Samuels, B., Graham, D., Kim, J. K., Shulman, G. I., Castle, A. L., Vinson, C., Eckhaus, M., & Reitman, M. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7901 · Cited by 676 · see citing works
Self-citationShapiro, L. S., & Scherer, P. E. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70133-2 · Cited by 652 · see citing works
Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome
Kissebah, A. H., Sonnenberg, G. E., Myklebust, J. B., Goldstein, M., Broman, K. W., James, R. G., Marks, J., Krakower, G. R., Jacob, H. J., Weber, J. L., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.26.14478 · Cited by 629 · see citing works
Matsuzawa, Y., Funahashi, T., & Nakamura, T. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07793.x · Cited by 601 · see citing works
Motojima, K., Passilly, P., Peters, J. M., Gonzalez, F. J., & Latruffe, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.27.16710 · Cited by 524 · see citing works
Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue.
White, R. T., Damm, D. L., Hancock, N., Rosen, B. S., Lowell, B. B., Usher, P., Flier, J. S., & Spiegelman, B. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50409-4 · Cited by 409 · see citing works
Improved insulin-sensitivity in mice heterozygous for PPAR-γ deficiency
Miles, P. D. G., Barak, Y., He, W., Evans, R. M., & Olefsky, J. M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8538 · Cited by 400 · see citing works
Generalized lipodystrophy, congenital and acquired (lipoatrophy)
Seip, M., & Trygstad, O. (1996) · Acta Paediatrica · doi:10.1111/j.1651-2227.1996.tb14262.x · Cited by 293 · see citing works
Yamauchi, T., Tobe, K., Tamemoto, H., Ueki, K., Kaburagi, Y., Yamamoto‐Honda, R., Takahashi, Y., Yoshizawa, F., Aizawa, S., Yasuo, A., et al. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.6.3074 · Cited by 288 · see citing works
Self-citationKelly, L. J., Vicario, P. P., Thompson, G. M., Candelore, M. R., Doebber, T. W., Ventre, J. R., Wu, M. S., Meurer, R. D., Forrest, M. J., Conner, M. W., et al. (1998) · Endocrinology · doi:10.1210/endo.139.12.6384 · Cited by 268 · see citing works
Murakami, K., Tobe, K., Ide, T., Mochizuki, T., Ohashi, M., Akanuma, Y., Yazaki, Y., & Kadowaki, T. (1998) · Diabetes · doi:10.2337/diabetes.47.12.1841 · Cited by 256 · see citing works
Self-citationGENETICS OF NON-INSULIN-DEPENDENT (TYPE-II) DIABETES MELLITUS
Kahn, C. R., Vicent, D., & Doria, A. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.509 · Cited by 211 · see citing works
Masuzaki, H., Ogawa, Y., Aizawa‐Abe, M., Hosoda, K., Suga, J., Ebihara, K., Satoh, N., Iwaï, H., Inoue, G., Nishimura, H., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1615 · Cited by 90 · see citing works
Retinoid X Receptor-Antagonistic Diazepinylbenzoic Acids.
Ebisawa, M., Umemiya, H., Ohta, K., Fukasawa, H., Kawachi, E., CHRISTOFFEL, G., Gronemeyer, H., Tsuji, M., Hashimoto, Y., SHUDO, K., et al. (1999) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.47.1778 · Cited by 87 · see citing works
Self-citationC1q—how many functions? How many receptors?
Eggleton, P. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01373-7 · Cited by 79 · see citing works
PPAR γ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance
窪田, 直. (2001) · Medical Entomology and Zoology · Cited by 44 · see citing works
Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity
Mondon, C. E., Dolkas, C. B., & OYAMA, J. (1981) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1981.240.5.e482 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522 · see citing works
Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326 · see citing works
Increased oxidative stress in obesity and its impact on metabolic syndrome
Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Nakayama, O., Makishima, M., Matsuda, M., & Shimomura, I. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21625 · Cited by 5,508 · see citing works
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 · see citing works
Self-citationInflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754 · see citing works
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690 · see citing works
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359 · see citing works
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003) · Nature · doi:10.1038/nature01705 · Cited by 3,176 · see citing works
Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome
Kadowaki, T. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29126 · Cited by 2,824 · see citing works
Self-citationAdiponectin and Adiponectin Receptors
Kadowaki, T., & Yamauchi, T. (2005) · Endocrine Reviews · doi:10.1210/er.2005-0005 · Cited by 2,634 · see citing works
Self-citationEndocrine regulation of energy metabolism by the skeleton
Lee, N. K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J. D., Confavreux, C., Dacquin, R., Mee, P. J., McKee, M. D., Jung, D. Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.047 · Cited by 2,554 · see citing works
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0039 · Cited by 2,232 · see citing works
Adipokines: inflammation and the pleiotropic role of white adipose tissue
Trayhurn, P., & Wood, I. S. (2004) · British Journal of Nutrition · doi:10.1079/bjn20041213 · Cited by 2,210 · see citing works
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · see citing works
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193 · see citing works
Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications
Fabbrini, E., Sullivan, S., & Klein, S. (2010) · Hepatology · doi:10.1002/hep.23280 · Cited by 2,100 · see citing works
Fat and Beyond: The Diverse Biology of PPARγ
Tontonoz, P., & Spiegelman, B. M. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061307.091829 · Cited by 2,085 · see citing works
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947 · see citing works
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 · see citing works
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention
Liu, R., Hong, J., Xu, X., Feng, Q., Zhang, D., Gu, Y., Shi, J., Zhao, S., Liu, W., Wang, X., et al. (2017) · Nature Medicine · doi:10.1038/nm.4358 · Cited by 1,501 · see citing works
Adipose tissue dysfunction in obesity, diabetes, and vascular diseases
Hajer, G. R., van Haeften, T. W., & Visseren, F. L. J. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn387 · Cited by 1,410 · see citing works
Fasting: molecular mechanisms and clinical applications
Longo, V. D., & Mattson, M. P. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.008 · Cited by 1,425 · see citing works
Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., Okada-Iwabu, M., Kawamoto, S., Kubota, N., Kubota, T., et al. (2007) · Nature Medicine · doi:10.1038/nm1557 · Cited by 1,396 · see citing works
Self-citationPeroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity
Wang, Y.-X., Lee, C.-H., Tiep, S., Yu, R. T., Ham, J., Kang, H., & Evans, R. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00269-1 · Cited by 1,296 · see citing works
Adipose Tissue Hypoxia in Obesity and Its Impact on Adipocytokine Dysregulation
Hosogai, N., Fukuhara, A., Oshima, K., Miyata, Y., Tanaka, S., Segawa, K., Furukawa, S., Tochino, Y., Komuro, R., Matsuda, M., et al. (2007) · Diabetes · doi:10.2337/db06-0911 · Cited by 1,257 · see citing works
Leptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247 · see citing works
Self-citationHomeostasis, Inflammation, and Disease Susceptibility
Kotas, M. E., & Medzhitov, R. (2015) · Cell · doi:10.1016/j.cell.2015.02.010 · Cited by 1,213 · see citing works
Adapting to obesity with adipose tissue inflammation
Reilly, S. M., & Saltiel, A. R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.90 · Cited by 1,204 · see citing works
Xu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317797 · Cited by 1,298 · see citing works
Role of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103 · see citing works
Rudic, R. D., McNamara, P., Curtis, A.-M., Boston, R. C., Panda, S., Hogenesch, J. B., & FitzGerald, G. A. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020377 · Cited by 1,059 · see citing works
Stern, J. H., Rutkowski, J. M., & Scherer, P. E. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.011 · Cited by 1,031 · see citing works
MicroRNAs 103 and 107 regulate insulin sensitivity
Trajkovski, M., Hausser, J., Soutschek, J., Bhat, B., Akin, A., Zavolan, M., Heim, M. H., & Stoffel, M. (2011) · Nature · doi:10.1038/nature10112 · Cited by 1,000 · see citing works
Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A., & Klein, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904944106 · Cited by 972 · see citing works
Adiponectin and AdipoR1 Regulate PGC-1α and Mitochondria by Ca2+ and AMPK/SIRT1
Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., Yamaguchi, M., Namiki, S., Nakayama, R., Tabata, M., et al. (2010) · Nature · doi:10.1038/nature08991 · Cited by 971 · see citing works
Trends in insulin resistance: insights into mechanisms and therapeutic strategy
Li, M., Chi, X., Wang, Y., Setrerrahmane, S., Xie, W., & Xu, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01073-0 · Cited by 939 · see citing works
Gender differences in insulin resistance, body composition, and energy balance
Geer, E. B., & Shen, W. (2009) · Gender Medicine · doi:10.1016/j.genm.2009.02.002 · Cited by 913 · see citing works
Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis
Yamauchi, T., Kamon, J., Waki, H., Imai, Y., Shimozawa, N., Hioki, K., Uchida, S., Ito, Y., Takakuwa, K., Matsui, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209033200 · Cited by 911 · see citing works
Self-citationFerron, M., Hinoi, E., Karsenty, G., & Ducy, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711119105 · Cited by 900 · see citing works
Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
Fernández-Real, J. M., & Ricart, W. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0010 · Cited by 886 · see citing works
Adiponectin Expression From Human Adipose Tissue
Kern, P. A., Di Gregorio, G. B., Lu, T., Rassouli, N., & Ranganathan, G. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1779 · Cited by 875 · see citing works
Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake
Kubota, N., Yano, W., Kubota, T., Yamauchi, T., Itoh, S., Kumagai, H., Kozono, H., Takamoto, I., Okamoto, S., Shiuchi, T., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.06.003 · Cited by 844 · see citing works
Self-citationAndrogens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein
Nishizawa, H., Shimomura, I., Kishida, K., Maeda, N., Kuriyama, H., Nagaretani, H., Matsuda, M., Kondo, H., Furuyama, N., Kihara, S., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.9.2734 · Cited by 837 · see citing works
Adiponectin acts in the brain to decrease body weight
Qi, Y., Takahashi, N., Hileman, S. M., Patel, H. R., Berg, A. H., Pajvani, U. B., Scherer, P. E., & Ahima, R. S. (2004) · Nature Medicine · doi:10.1038/nm1029 · Cited by 809 · see citing works
Kim, K. H., Jeong, Y. T., Oh, H., Kim, S. H., Cho, J. M., Kim, Y.-N., Kim, S. S., Kim, D. H., Hur, K. Y., Kim, H. K., et al. (2013) · Nature Medicine · doi:10.1038/nm.3014 · Cited by 774 · see citing works
Minireview: Adiposity, Inflammation, and Atherogenesis
Lyon, C. J., Law, R. E., & Hsueh, W. A. (2003) · Endocrinology · doi:10.1210/en.2003-0285 · Cited by 761 · see citing works
Ouchi, N., Kobayashi, H., Kihara, S., Kumada, M., Sato, K., Inoue, T., Funahashi, T., & Walsh, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310389200 · Cited by 759 · see citing works
A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity
Okada-Iwabu, M., Yamauchi, T., Iwabu, M., Honma, T., Hamagami, K.-I., Matsuda, K., Yamaguchi, M., Tanabe, H., Kimura-Someya, T., Shirouzu, M., et al. (2013) · Nature · doi:10.1038/nature12656 · Cited by 757 · see citing works
Self-citationAdipose tissue as a buffer for daily lipid flux
Frayn, K. (2002) · Diabetologia · doi:10.1007/s00125-002-0873-y · Cited by 752 · see citing works
Angiogenesis modulates adipogenesis and obesity
Cao, Y. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32239 · Cited by 736 · see citing works
Obesity and cancer: the role of dysfunctional adipose tissue
van Kruijsdijk, R. C. M., van der Wall, E., & Visseren, F. L. J. (2009) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-09-0372 · Cited by 715 · see citing works
Adipocytokines in Obesity and Metabolic Disease
Cao, H. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0339 · Cited by 705 · see citing works
Targeting adipose tissue in the treatment of obesity-associated diabetes
Kusminski, C. M., Bickel, P. E., & Scherer, P. E. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.75 · Cited by 678 · see citing works
Lin, Z., Tian, H., Lam, K. S. L., Lin, S., Hoo, R. C. L., Konishi, M., Itoh, N., Wang, Y., Bornstein, S. R., Xu, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.005 · Cited by 691 · see citing works
Gestational diabetes: The consequences of not treating
Langer, O., Yogev, Y., Most, O., & Xenakis, E. M. J. (2005) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.11.039 · Cited by 677 · see citing works
Pathogenesis of insulin resistance in skeletal muscle
Abdul-Ghani, M. A., & DeFronzo, R. A. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/476279 · Cited by 670 · see citing works
Bays, H., Mandarino, L., & DeFronzo, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030723 · Cited by 664 · see citing works
Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation
Fu, Y., Luo, N., Klein, R. L., & Garvey, W. T. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400373-jlr200 · Cited by 666 · see citing works
Adiponectin: action, regulation and association to insulin sensitivity
Lihn, A. S., Pedersen, S. B., & Richelsen, B. (2005) · Obesity Reviews · doi:10.1111/j.1467-789x.2005.00159.x · Cited by 660 · see citing works
Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes
Fasshauer, M., Klein, J., Neumann, S., Eszlinger, M., & Paschke, R. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6307 · Cited by 655 · see citing works
Mayerson, A. B., Hundal, R. S., Dufour, S., Lebon, V., Befroy, D., Cline, G. W., Enocksson, S., Inzucchi, S. E., Shulman, G. I., & Petersen, K. F. (2002) · Diabetes · doi:10.2337/diabetes.51.3.797 · Cited by 647 · see citing works
Adiponectin regulation and function
Fang, H., & Judd, R. L. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170046 · Cited by 631 · see citing works
The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic
Geng, L., Lam, K. S. L., & Xu, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0386-0 · Cited by 607 · see citing works
Adiponectin, the past two decades
Wang, Z. V., & Scherer, P. E. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw011 · Cited by 609 · see citing works
The inflammation highway: metabolism accelerates inflammatory traffic in obesity
Johnson, A. R., Justin Milner, J., & Makowski, L. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01151.x · Cited by 603 · see citing works
Leptin in Human Physiology and Pathophysiology
Mantzoros, C. S., Magkos, F., Brinkoetter, M., Sienkiewicz, E., Dardeno, T. A., Kim, S.-Y., Hamnvik, O.-P. R., & Koniaris, A. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00315.2011 · Cited by 593 · see citing works
Obesity as a cardiovascular risk factor
Sowers, J. R. (2003) · The American Journal of Medicine · doi:10.1016/j.amjmed.2003.08.012 · Cited by 584 · see citing works
Havel, P. J. (2002) · Current Opinion in Lipidology · doi:10.1097/00041433-200202000-00008 · Cited by 575 · see citing works
Recent insights into the pathogenesis of nonalcoholic fatty liver disease
Arab, J. P., Arrese, M., & Trauner, M. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043617 · Cited by 573 · see citing works
Tsuchida, A., Yamauchi, T., Ito, Y., Hada, Y., Maki, T., Takekawa, S., Kamon, J., Kobayashi, M., Suzuki, R., Hara, K., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402367200 · Cited by 550 · see citing works
Self-citationCombs, T. P., Berg, A. H., Rajala, M. W., Klebanov, S., Iyengar, P., Jimenez-Chillaron, J. C., Patti, M. E., Klein, S. L., Weinstein, R. S., & Scherer, P. E. (2003) · Diabetes · doi:10.2337/diabetes.52.2.268 · Cited by 544 · see citing works
Yoon, M. J., Lee, G. Y., Chung, J.-J., Ahn, Y. H., Hong, S. H., & Kim, J. B. (2006) · Diabetes · doi:10.2337/db05-1322 · Cited by 546 · see citing works
The obese adipose tissue microenvironment in cancer development and progression
Quail, D. F., & Dannenberg, A. J. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0126-x · Cited by 542 · see citing works
Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo
Kim, H.-J., Higashimori, T., Park, S.-Y., Choi, H., Dong, J., Kim, Y.-J., Noh, H.-L., Cho, Y.-R., Cline, G., Kim, Y.-B., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.4.1060 · Cited by 534 · see citing works
Tiikkainen, M., Häkkinen, A.-M., Korsheninnikova, E., Nyman, T., Mäkimattila, S., & Yki-Järvinen, H. (2004) · Diabetes · doi:10.2337/diabetes.53.8.2169 · Cited by 524 · see citing works
Thiazolidinediones, Like Metformin, Inhibit Respiratory Complex I
Brunmair, B., Staniek, K., Gras, F., Scharf, N., Althaym, A., Clara, R., Roden, M., Gnaiger, E., Nohl, H., Waldhäusl, W., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.4.1052 · Cited by 521 · see citing works
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. (2004) · Diabetes · doi:10.2337/diabetes.53.4.931 · Cited by 512 · see citing works
Licinio, J., Caglayan, S., Ozata, M., Yildiz, B. O., de Miranda, P. B., O'Kirwan, F., Whitby, R., Liang, L., Cohen, P., Bhasin, S., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308767101 · Cited by 505 · see citing works
Liu, C., Feng, X., Li, Q., Wang, Y., Li, Q., & Hua, M. (2016) · Cytokine · doi:10.1016/j.cyto.2016.06.028 · Cited by 470 · see citing works
Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?
Trayhurn, P., Wang, B., & Wood, I. S. (2008) · British Journal of Nutrition · doi:10.1017/s0007114508971282 · Cited by 464 · see citing works
AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome
Ruderman, N., & Prentki, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1344 · Cited by 451 · see citing works
Cnop, M., Landchild, M. J., Vidal, J., Havel, P. J., Knowles, N. G., Carr, D. R., Wang, F., Hull, R. L., Boyko, E. J., Retzlaff, B. M., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1005 · Cited by 432 · see citing works
Insulin resistance as the core defect in type 2 diabetes mellitus
Goldstein, B. J. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02553-5 · Cited by 432 · see citing works
Association between adiponectin and mediators of inflammation in obese women
Engeli, S., Feldpausch, M., Gorzelniak, K., Hartwig, F., Heintze, U., Janke, J., Möhlig, M., Pfeiffer, A. F. H., Luft, F. C., & Sharma, A. M. (2003) · Diabetes · doi:10.2337/diabetes.52.4.942 · Cited by 422 · see citing works
Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance
Netea, M. G., Joosten, L. A. B., Lewis, E., Jensen, D. R., Voshol, P. J., Kullberg, B. J., Tack, C. J., van Krieken, H., Kim, S.-H., Stalenhoef, A. F., et al. (2006) · Nature Medicine · doi:10.1038/nm1415 · Cited by 424 · see citing works
Endothelial Dysfunction in Obesity and Insulin Resistance: A Road to Diabetes and Heart Disease
Caballero, A. E. (2003) · Obesity Research · doi:10.1038/oby.2003.174 · Cited by 416 · see citing works
Adiponectin Replenishment Ameliorates Obesity-Related Hypertension
Ohashi, K., Kihara, S., Ouchi, N., Kumada, M., Fujita, K., Hiuge, A., Hibuse, T., Ryo, M., Nishizawa, H., Maeda, N., et al. (2006) · Hypertension · doi:10.1161/01.hyp.0000222368.43759.a1 · Cited by 400 · see citing works
Adiponectin signaling and function in insulin target tissues
Ruan, H., & Dong, L. Q. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw014 · Cited by 395 · see citing works
den Hartigh, L. (2019) · Nutrients · doi:10.3390/nu11020370 · Cited by 371 · see citing works
Adiponectin and Future Coronary Heart Disease Events Among Men With Type 2 Diabetes
Schulze, M. B., Shai, I., Rimm, E. B., Li, T., Rifai, N., & Hu, F. B. (2005) · Diabetes · doi:10.2337/diabetes.54.2.534 · Cited by 365 · see citing works
Hormonal regulation of food intake
Stanley, S., Wynne, K., McGowan, B., & Bloom, S. (2005) · Physiological Reviews · doi:10.1152/physrev.00015.2004 · Cited by 372 · see citing works
Association of the T-G Polymorphism in Adiponectin (Exon 2) With Obesity and Insulin Sensitivity
Stumvoll, M., Tschritter, O., Fritsche, A., Staiger, H., Renn, W., Weisser, M., Machicao, F., & Häring, H. (2002) · Diabetes · doi:10.2337/diabetes.51.1.37 · Cited by 371 · see citing works
Li, X. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms108 · Cited by 360 · see citing works
Wong, G. W., Krawczyk, S. A., Kitidis-Mitrokostas, C., Revett, T., Gimeno, R., & Lodish, H. F. (2008) · Biochemical Journal · doi:10.1042/bj20081240 · Cited by 371 · see citing works
Short sleep duration and cardiometabolic risk: from pathophysiology to clinical evidence
Tobaldini, E., Fiorelli, E. M., Solbiati, M., Costantino, G., Nobili, L., & Montano, N. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0109-6 · Cited by 357 · see citing works
Adiponectin, the missing link in insulin resistance and obesity
GILCAMPOS, M. (2004) · Clinical Nutrition · doi:10.1016/j.clnu.2004.04.010 · Cited by 353 · see citing works
The “Big Bang” in obese fat: events initiating obesity-induced adipose tissue inflammation
Wensveen, F. M., Valentić, S., Šestan, M., Turk Wensveen, T., & Polić, B. (2015) · European Journal of Immunology · doi:10.1002/eji.201545502 · Cited by 348 · see citing works
Obesity-related derangements in metabolic regulation
Muoio, D. M., & Newgard, C. B. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142512 · Cited by 345 · see citing works
Shibata, R., Ouchi, N., Kihara, S., Sato, K., Funahashi, T., & Walsh, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402558200 · Cited by 336 · see citing works
- Authors
- Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., Ezaki, O., Akanuma, Y., Gavrilova, O., Vinson, C., Reitman, M. L., Kagechika, H., Shudo, K., Yoda, M., Nakano, Y., Tobe, K., Nagai, R., Kimura, S., Tomita, M., Froguel, P., & Kadowaki, T.
- Affiliations
- The University of Tokyo (JP)
- Centre National de la Recherche Scientifique (FR)
- National Institute of Health and Nutrition (JP)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Institutes of Health (US)
- SHOWA Medical University (JP)
- Corresponding author
- Kadowaki, T.
- ORCID
- Venue
- Nature Medicine
- Published
- 2001-08
- Volume
- 7
- Issue
- 8
- Pages
- 941-946
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1587875569
- Cited by
- 4,915
- References
- 38
- Citations by year
- 2026: 48 · 2025: 75 · 2024: 100 · 2023: 127 · 2022: 125 · 2021: 127 · 2020: 214 · 2019: 168 · 2018: 152 · 2017: 157 · 2016: 203 · 2015: 208 · 2014: 198 · 2013: 258 · 2012: 229
- FWCI
- 160.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- adiponectin, insulin resistance, lipoatrophy, obesity, type 2 diabetes, leptin, triglyceride content, muscle, liver, fatty acid oxidation, energy dissipation, chromosome 3q27, metabolic syndrome, adipokines
- MeSH terms
- Adipose Tissue, Amino Acid Sequence, Animals, Insulin Resistance, Molecular Sequence Data, Obesity, Oxidation-Reduction, Proteins, Transcription Factors, Triglycerides, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Leptin, Intercellular Signaling Peptides and Proteins, Mice, Adiponectin
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
