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Unraveling the Temporal Pattern of Diet-Induced Insulin Resistance in Individual Organs and Cardiac Dysfunction in c57bl/6 Mice
Abstract
Type 2 diabetes is a heterogeneous disease characterized by insulin resistance and altered glucose and lipid metabolism in multiple organs. To understand the complex series of events that occur during the development of obesity-associated diabetes, we examined the temporal pattern of changes in insulin action and glucose metabolism in individual organs during chronic high-fat feeding in C57BL/6 mice. Insulin-stimulated cardiac glucose metabolism was significantly reduced after 1.5 weeks of high-fat feeding, and cardiac insulin resistance was associated with blunted Akt-mediated insulin signaling and GLUT4 levels. Insulin resistance in skeletal muscle, adipose tissue, and liver developed in parallel after 3 weeks of high-fat feeding. Diet-induced whole-body insulin resistance was associated with increased circulating levels of resistin and leptin but unaltered adiponectin levels. High-fat feeding caused insulin resistance in skeletal muscle that was associated with significantly elevated intramuscular fat content. In contrast, diet-induced hepatic insulin resistance developed before a marked increase in intrahepatic triglyceride levels. Cardiac function gradually declined over the course of high-fat feeding, and after 20 weeks of high-fat diet, cardiac dysfunction was associated with mild hyperglycemia, hyperleptinemia, and reduced circulating adiponectin levels. Our findings demonstrate that cardiac insulin resistance is an early adaptive event in response to obesity and develops before changes in whole-body glucose homeostasis. This suggests that obesity-associated defects in cardiac function may not be due to insulin resistance per se but may be attributable to chronic alteration in cardiac glucose and lipid metabolism and circulating adipokines.
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“In contrast, high-fat feeding that is associated with the development of insulin resistance and obesity is associated with development of LV dysfunction in many (269, 273, 296) but not all studies (40).”
From Cardiac remodeling in obesity (2008) · cites this paper as [273]
In the citing paper
“Thus C57BL6 mice when placed on a high-fat diet develop LV dysfunction as evidenced by reduced fractional shortening only after 20 wk of high-fat feeding (273).”
From Cardiac remodeling in obesity (2008) · cites this paper as [273]
In the citing paper
“This was addressed by Kim’s group via a high-fat feeding regimen in mice (273). They found that obesity-associated defects in cardiac function did not develop in concert with insulin resistance and concluded that changes in circulating adipokines could be an important contributing factor in cardiac dysfunction.”
From Cardiac remodeling in obesity (2008) · cites this paper as [273]
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Cites
Wild, S., Roglic, G., Green, A., Sicree, R., & King, H. (2004) · Diabetes Care · doi:10.2337/diacare.27.5.1047 · Cited by 15,297
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154
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
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 mechanisms of action of PPARs
Berger, J., & Moller, D. E. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104018 · Cited by 2,659
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Self-citationKern, P. A., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e745 · Cited by 1,883
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,860
Self-citationRole of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728
Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
Samuel, V. T., Liu, Z.-X., Qu, X., Elder, B. D., Bilz, S., Befroy, D., Romanelli, A. J., & Shulman, G. I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313478200 · Cited by 1,322
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Diabetic Cardiomyopathy Revisited
Boudina, S., & Abel, E. D. (2007) · Circulation · doi:10.1161/circulationaha.106.679597 · Cited by 1,543
Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease
Mehlem, A., Hagberg, C. E., Muhl, L., Eriksson, U., & Falkevall, A. (2013) · Nature Protocols · doi:10.1038/nprot.2013.055 · Cited by 917
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736
“ing only after 20 wk of high-fat feeding (273).”
BackgroundMethodInfluentialLipid Metabolism and Toxicity in the Heart
Goldberg, I. J., Trent, C. M., & Schulze, P. C. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.006 · Cited by 601
“Mice fed a high-fat diet rapidly develop cardiac insulin resistance, suggesting that lipid accumulation rapidly causes changes in heart metabolism allowing it to rely more on FAs as its fuel (Park et al., 2005).”
Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
Mehran, A. E., Templeman, N. M., Brigidi, G. S., Lim, G. E., Chu, K.-Y., Hu, X., Botezelli, J. D., Asadi, A., Hoffman, B. G., Kieffer, T. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.019 · Cited by 498
Insulin resistance causes inflammation in adipose tissue
Shimobayashi, M., Albert, V., Woelnerhanssen, B., Frei, I. C., Weissenberger, D., Meyer-Gerspach, A. C., Clement, N., Moes, S., Colombi, M., Meier, J. A., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96139 · Cited by 480
“These findings are consistent with previous reports showing that mice develop adipose and systemic insulin resistance within several days to 4 weeks of a HFD (44, 45), whereas the number of M1 macrophages in WAT increases only within 8 to 10 weeks of a HFD (10, 15, 45, 46).”
ResultTurner, N., Kowalski, G. M., Leslie, S. J., Risis, S., Yang, C., Lee-Young, R. S., Babb, J. R., Meikle, P. J., Lancaster, G. I., Henstridge, D. C., et al. (2013) · Diabetologia · doi:10.1007/s00125-013-2913-1 · Cited by 430
“Other rodent studies using HFDs with differing lipid content and composition have reported a similar temporal pattern of the development of tissue-specific insulin resistance [7, 19, 20], indicating that insulin-regulated glucose metabolism in liver and adipose tissue are particularly sensitive to the effects of dieta…”
BackgroundHong, E., Ko, H. J., Cho, Y.-R., Kim, H., Ma, Z., Yu, T. Y., Friedline, R. H., Kurt‐Jones, E. A., Finberg, R. W., Fischer, M. A., et al. (2009) · Diabetes · doi:10.2337/db08-1261 · Cited by 421
“We have previously shown that lipid-mediated insulin resistance involves defects in muscle insulin signaling (29,30).”
Self-citationObesity cardiomyopathy: evidence, mechanisms, and therapeutic implications
Ren, J. T., Wu, N. N., Wang, S., Sowers, J. R., & Zhang, Y. (2021) · Physiological Reviews · doi:10.1152/physrev.00030.2020 · Cited by 388
Kim, F., Pham, M., Maloney, E., Rizzo, N. O., Morton, G. J., Wisse, B. E., Kirk, E. A., Chait, A., & Schwartz, M. W. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.169722 · Cited by 364
Lipid Use and Misuse by the Heart
Schulze, P. C., Drosatos, K., & Goldberg, I. J. (2016) · Circulation Research · doi:10.1161/circresaha.116.306842 · Cited by 367
Balagopal, P., de Ferranti, S. D., Cook, S., Daniels, S. R., Gidding, S. S., Hayman, L. L., McCrindle, B. W., Mietus‐Snyder, M., & Steinberger, J. (2011) · Circulation · doi:10.1161/cir.0b013e31821c7c64 · Cited by 363
Wende, A. R., & Abel, E. D. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.023 · Cited by 352
“This metabolic switch precedes contractile dysfunction which does not develop until after 20 wk of HFD feeding [74].”
Boudina, S., Bugger, H., Sena, S., O'Neill, B. T., Zaha, V. G., Ilkun, O., Wright, J. J., Mazumder, P. K., Palfreyman, E., Tidwell, T. J., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.792101 · Cited by 301
Palomer, X., Salvadó, L., Barroso, E., & Vázquez‐Carrera, M. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.07.150 · Cited by 290
“owing to the excess lipid supply, which in turn will increase lipid utilization and reduce glucose metabolism in the heart [59].”
BackgroundBrookheart, R. T., Michel, C. I., & Schaffer, J. E. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.011 · Cited by 279
“…of findings from leptin-deficient models to human obesity and diabetes has been debated, lipid accumulation and cell death in nonadipose tissues of murine models of diet-induced obesity are consistent with a role for lipid accumulation in the pathogenesis of organ dysfunction (Park et al., 2005).”
BackgroundVisceral fat and metabolic inflammation: the portal theory revisited
Item, F., & Konrad, D. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01035.x · Cited by 287
“As a consequence, insulin sensitivity is impaired locally and systemically (44,69,70).”
BackgroundCardiac lipid metabolism, mitochondrial function, and heart failure
Dalt, L. D., Cabodevilla, A. G., Goldberg, I. J., & Norata, G. D. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvad100 · Cited by 264
Adropin Deficiency Is Associated With Increased Adiposity and Insulin Resistance
Kumar, K. G., Zhang, J., Gao, S., Rossi, J., McGuinness, O. P., Halem, H. H., Culler, M. D., Mynatt, R. L., & Butler, A. A. (2012) · Obesity · doi:10.1038/oby.2012.31 · Cited by 262
“Mice-fed HFD were obese, exhibiting increased body weight compared to controls fed LFD (41.0 ± 1.4g vs. 30.9 ± 0.8 g, P 0.001).”
BackgroundInfluentialZhang, L., Keung, W., Samokhvalov, V., Wang, W. J., & Lopaschuk, G. D. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.014 · Cited by 276
“cardiac TG in obesity [13,32,88,89,210], unchanged long chain acyl CoA [211] and increased [89] or decreased ceramide levels [210] in”
BackgroundMaladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance
Aroor, A. R., McKarns, S. C., DeMarco, V. G., Jia, G., & Sowers, J. R. (2013) · Metabolism · doi:10.1016/j.metabol.2013.07.001 · Cited by 243
“Moreover, insulin resistance develops in the heart of C57BL/6 mice as early as ten days after high-fat feeding, before the onset of insulin resistance in the skeletal muscle and liver which occur after three weeks of high-fat feeding [42].”
BackgroundRecipes for Creating Animal Models of Diabetic Cardiovascular Disease
Hsueh, W. A., Abel, E. D., Breslow, J. L., Maeda, N., Davis, R. C., Fisher, E. A. A., Dansky, H. M., McClain, D. A., McIndoe, R., Wassef, M. K., et al. (2007) · Circulation Research · doi:10.1161/01.res.0000266449.37396.1f · Cited by 221
Cardiac Lipotoxicity: Molecular Pathways and Therapeutic Implications
Drosatos, K., & Schulze, P. C. (2013) · Current Heart Failure Reports · doi:10.1007/s11897-013-0133-0 · Cited by 224
“Insulin resistance is one of the earliest observed cardiac defects found in mice given a high-fat diet [88].”
Shao, D., Kolwicz, S. C., Wang, P., Roe, N. D., Villet, O. M., Nishi, K., Hsu, Y. A., Flint, G. V., Caudal, A., Wang, W., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.043319 · Cited by 217
Free fatty acids and skeletal muscle insulin resistance
Kraegen, E. W., & Cooney, G. J. (2008) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000319118.44995.9a · Cited by 210
Mitochondrial Uncoupling: A Key Contributor to Reduced Cardiac Efficiency in Diabetes
Boudina, S., & Abel, E. D. (2006) · Physiology · doi:10.1152/physiol.00008.2006 · Cited by 199
Cardiovascular effects of leptin
Sweeney, G. (2009) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2009.224 · Cited by 186
“Changes in hypertrophy were demonstrated to be of functional consequence in diet-induced obesity”
BackgroundMuniyappa, R., Chen, H., Muzumdar, R. H., Einstein, F. H., Xu, Y., Yue, L. Q., Barzilai, N., & Quon, M. J. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00397.2009 · Cited by 179
Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding
Wright, J. J., Kim, J., Buchanan, J., Boudina, S., Sena, S., Bakirtzi, K., Ilkun, O. L., Theobald, H. A., Cooksey, R. C., Kandror, K. V., et al. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp017 · Cited by 179
“Ten days of high-fat feeding in C57BL6 mice reduced insulinmediated glucose uptake in proportion to reduced glucose transporter 4 (GLUT4), and reduced protein kinase B (Akt/PKB) phosphorylation.(20) In this study, the metabolic fate of FA and glucose in the heart and expression of PPAR-a targets were not determined.”
BackgroundSelf-citationHigh-fat diet-induced β-cell proliferation occurs prior to insulin resistance in C57Bl/6J male mice
Mosser, R. E., Maulis, M. F., Moullé, V. S., Dunn, J. C., Carboneau, L., Arasi, K., Pappan, K. L., Poitout, V., & GANNON, M. A. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00460.2014 · Cited by 177
Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice
Zheng, S., Hoos, L. M., Cook, J., Tetzloff, G. G., Davis, H. R., van Heek, M., & Hwa, J. J. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.01.045 · Cited by 167
Calligaris, S. D., Lecanda, M., Solis, F., Ezquer, M., Gutiérrez, J., Brandan, E., Leiva, A., Sobrevía, L., & Conget, P. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060931 · Cited by 162
“It has been shown that a high-sucrose diet exacerbates insulin resistance [6], a high-salt or high-fructose diet exacerbates hypertension [7,8], a high-cholesterol diet exacerbates atherosclerosis [9], and a short-term high-fat diet results in discrete systolic dysfunction [10].”
BackgroundTurner, N. A., Hariharan, K., Tid-Ang, J. D., Frangioudakis, G., Beale, S. M., Wright, L. E., Zeng, X., Leslie, S. J., Li, J.-Y., Kraegen, E. W., et al. (2009) · Diabetes · doi:10.2337/db09-0784 · Cited by 162
“Many studies have demonstrated that consumption of a diet high in long-chain fatty acids (LCFA) induces widespread insulin resistance in muscle, liver and adipose tissue of both rats and mice (4-7).”
Wueest, S., Rapold, R. A., Schumann, D., Rytka, J. M., Schildknecht, A., Nov, O., Chervonsky, A. V., Rudich, A., Schoenle, E. J., Donath, M. Y., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38388 · Cited by 161
High-fat diet selectively protects against the effects of chronic social stress in the mouse
Finger, B. C., Dinan, T. G., & Cryan, J. F. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.072 · Cited by 169
“Insulin and leptin both play major role in the development of diet-induced obesity, here animals after long-term exposure to the high-fat diet evelop insulin and leptin resistance (Park et al., 2005; orrison et al., 2009).”
Ko, H. J., Zhang, Z., Jung, D. Y., Jun, J. Y., Ma, Z., Jones, K. E., Chan, S. Y., & Kim, J. K. (2009) · Diabetes · doi:10.2337/db08-1361 · Cited by 160
Self-citationLee, S., Muniyappa, R., Xu, Y., Chen, H., Yue, L. Q., Hong, E., Kim, J. K., & Quon, M. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00676.2007 · Cited by 158
“Metabolic phenotyping and comparison of glucose metabolism between the specific models of insulin resistance and sensitivity and their respective wild-type littermates have been previously published (10, 16, 24, 25, 33, 36).”
BackgroundMethodInfluentialSelf-citationWilson, C. R., Tran, M. K., Salazar, K. L., Young, M. E., & Taegtmeyer, H. (2007) · Biochemical Journal · doi:10.1042/bj20070392 · Cited by 156
Renalase deficiency aggravates ischemic myocardial damage
Wu, Y., Xu, J., Velázquez, H., Wang, P., Li, G., Liu, D., Sampaio‐Maia, B., Quelhas‐Santos, J., Russell, K. S., Russell, R. R., et al. (2010) · Kidney International · doi:10.1038/ki.2010.488 · Cited by 152
Self-citationNew insights into insulin resistance in the diabetic heart
Gray, S., & Kim, J. K. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.05.001 · Cited by 147
“However, a chronic state of insulin resistance and dysregulated metabolism may induce a pathological event involving cardiac remodeling and systolic dysfunction, which were observed in C57BL/6 mice after 20 weeks of high-fat feeding [46].”
InfluentialSelf-citationManifestations and mechanisms of myocardial lipotoxicity in obesity
Sletten, A. C., Peterson, L. R., & Schaffer, J. E. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12728 · Cited by 148
Intramuscular Fat and Associations With Metabolic Risk Factors in the Framingham Heart Study
Therkelsen, K. E., Pedley, A., Speliotes, E. K., Massaro, J. M., Murabito, J. M., Hoffmann, U., & Fox, C. S. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.301009 · Cited by 140
“Comparatively, on the same high-fat diet, liver insulin resistance preceded increased intrahepatic fat.(20) Therefore, intramuscular fat may be more closely associated with insulin resistance than other ectopic fats, such as intrahepatic fat.”
BackgroundStamateris, R. E., Sharma, R. B., Hollern, D. A., & Alonso, L. C. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00040.2013 · Cited by 138
“5 and 3 wk of HFD (46), supporting the possibility that our data are correct.”
BackgroundSutton, G. M., Trevaskis, J. L., Hulver, M. W., McMillan, R. P., Markward, N., Babin, M. J., Meyer, E. A., & Butler, A. A. (2006) · Endocrinology · doi:10.1210/en.2005-1209 · Cited by 141
Sears, D. D., Miles, P. D. G., Chapman, J., Ofrecio, J. M., Almazan, F., Thapar, D., & Miller, Y. I. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007250 · Cited by 135
“studied model of insulin resistance in rodents, rapidly causes progressive metabolic maladies [4,5].”
BackgroundThe cafeteria diet: A standardized protocol and its effects on behavior
Lalanza, J. F., & Snoeren, E. M. S. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.11.003 · Cited by 156
“For example, 3 weeks of HF/HS diet was induced skeletal muscle insulin resistance (Park et al., 2005), but 6− 8 weeks were necessary to achieve a stably obese body in rodents (Heyne et al., 2009).”
BackgroundCD36 Expression Contributes to Age-Induced Cardiomyopathy in Mice
Koonen, D. P. Y., Febbraio, M., Bonnet, S., Nagendran, J., Young, M. E., Michelakis, E. D., & Dyck, J. R. B. (2007) · Circulation · doi:10.1161/circulationaha.107.712901 · Cited by 137
Dietary Fat and Heart Failure: Moving From Lipotoxicity to Lipoprotection
Stanley, W. C., Dabkowski, E. R., Júnior, R. F. R., & O’Connell, K. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.253104 · Cited by 133
Tam, C. S., Viardot, A., Clément, K., Tordjman, J., Tonks, K. T. T., Greenfield, J. R., Campbell, L. V., Samocha‐Bonet, D., & Heilbronn, L. K. (2010) · Diabetes · doi:10.2337/db10-0162 · Cited by 126
“However, the gold standard measure of insulin sensitivity, the hyperinsulinemic clamp, was not performed in this study and insulin resistance measured by clamp or by 2-deoxyglucose uptake is impaired as early as 3 weeks after initiation of HFD in rodents (29,30).”
BackgroundAdaptation and maladaptation of the heart in obesity
Harmancey, R., Wilson, C. R., & Taegtmeyer, H. (2008) · Hypertension · doi:10.1161/hypertensionaha.108.110031 · Cited by 121
Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction
Thakker, G. D., Frangogiannis, N. G., Bujak, M., Zymek, P., Gaubatz, J. W., Reddy, A. K., Taffet, G., Michael, L. H., Entman, M. L., & Ballantyne, C. M. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00322.2006 · Cited by 121
“Long-term (20 weeks) feeding was associated with LV systolic dysfunction and mild hyperglycemia, hyperleptinemia and reduced circulating adiponectin levels (43).”
BackgroundMetabolomic profiling of dietary‐induced insulin resistance in the high fat–fed C57BL/6J mouse
Shearer, J., Duggan, G. E., Weljie, A. M., Hittel, D. S., Wasserman, D. H., & Vogel, H. J. (2008) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2007.00837.x · Cited by 119
Leptin and incident type 2 diabetes: risk or protection?
Schmidt, M. I., Duncan, B. B., Vigo, Á., Pankow, J. S., Couper, D. J., Ballantyne, C. M., Hoogeveen, R. C., HEISS, G. M., & For the ARIC Investigators (2006) · Diabetologia · doi:10.1007/s00125-006-0351-z · Cited by 118
“(and or specific patterns of eating) [39–41] and a sedentary lifestyle [42, 43], lead to leptin resistance with resulting hyperleptinaemia.”
An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart
Fang, X., Palanivel, R., Cresser, J., Schram, K., Ganguly, R., Thong, F. S. L., Tuinei, J., Xu, A., Abel, E. D., & Sweeney, G. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00086.2010 · Cited by 119
“Changes in myocardial energy metabolism are one of the earliest measurable abnormalities in the hearts of obese animals or humans and precedes measurable changes in in vivo cardiac function (1, 7, 16, 31, 32, 41).”
BackgroundSelective Insulin Resistance in Adipocytes
Tan, S., Fisher‐Wellman, K. H., Fazakerley, D. J., Ng, Y., Pant, H., Li, J., Meoli, C. C., Coster, A. C. F., Stöckli, J., & James, D. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.623686 · Cited by 116
“Consistent with previous studies (36, 45), C57BL/6J mice fed a high fat diet (HFD) for 28 days displayed a significant impairment in whole body glucose tolerance (Fig.”
ResultExcess protein O-GlcNAcylation and the progression of diabetic cardiomyopathy
Fricovsky, E. S., Suárez, J., Ihm, S., Scott, B. T., Suarez-Ramirez, J. A., Banerjee, I., Torres‐Gonzalez, M., Wang, H., Ellrott, I., Maya-Ramos, L., et al. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00548.2011 · Cited by 112
Fatty Heart, Cardiac Damage, and Inflammation
Guzzardi, M. A., & Iozzo, P. (2011) · The Review of Diabetic Studies · doi:10.1900/rds.2011.8.403 · Cited by 114
“It precedes the onset of cardiac dysfunction, and it is related to the phosphorylation and activation of protein kinase B (PKB/Akt) signaling, which regulates insulin sensitivity [8, 14].”
BackgroundImpact of obesity on cardiac metabolism, fibrosis, and function
Mahajan, R., Lau, D. H., & Sanders, P. (2014) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2014.09.005 · Cited by 109
“[16] Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, et al.”
BackgroundInflammation in Metabolic Cardiomyopathy
Wenzl, F. A., Ambrosini, S., Mohammed, S. A., Kraler, S. C., Lüscher, T. F., Costantino, S., & Paneni, F. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.742178 · Cited by 115
Kwon, E., Shin, S., Cho, Y.-Y., Jung, U. J., Kim, E., Park, T., Park, J. H. Y., Yun, J. W., McGregor, R. A., Park, Y. B., et al. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-450 · Cited by 111
“In accordance with our results, Park and colleague’s reported that circulating adiponectin level was significantly reduced after 20 weeks of high-fat feeding (55 kcal% from fat) compared with a normal diet [35].”
ResultSelf-citationThe Impact of Dietary Methionine Restriction on Biomarkers of Metabolic Health
Orgeron, M., Stone, K. P., Wanders, D., Cortez, C. C., Van, N. T., & Gettys, T. W. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-800101-1.00011-9 · Cited by 110
Ostler, J. E., Maurya, S. K., Dials, J., Roof, S. R., Devor, S. T., Ziolo, M. T., & Periasamy, M. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00277.2013 · Cited by 102
“The relatively mild diabetic phenotype of diet-induced obesity mice compared with humans and other models of T2DM may account for the paucity of muscle pathology in HFD-fed mice (38).”
BackgroundD'Eon, T. M., Pierce, K. A., Roix, J. J., Tyler, A., Chen, H., & Teixeira, S. R. (2008) · Diabetes · doi:10.2337/db07-1186 · Cited by 102
“Previous studies have demonstrated adipose tissue insulin resistance in C57 Bl6 mice on high fat diet as early as 3 weeks on diet (24).”
BackgroundThe Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress
Włodarski, A., Strycharz, J., Wróblewski, A. M., Kasznicki, J., Drzewoski, J., & Śliwińska, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186902 · Cited by 99
“It has been well-characterized that HFD-fed C57BL/6 mice develop skeletal muscle IR [208,209].”
BackgroundBurchfield, J. G., Kebede, M. A., Meoli, C. C., Stöckli, J., Whitworth, P. T., Wright, A. L., Hoffman, N. J., Minard, A. Y., Ma, X., Krycer, J. R., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000808 · Cited by 97
“In agreement with other longitudinal studies [23-26], our analysis did not detect any significant changes in glucose tolerance, fasting or fed circulating insulin levels, 2DG glucose uptake into adipocytes and muscle or glucose stimulated insulin secretion in these mice throughout the 60 week feeding period.”
ResultChronic high fat diet induces cardiac hypertrophy and fibrosis in mice
Wang, Z., Li, L., Zhao, H., Peng, S., & Zuo, Z. (2015) · Metabolism · doi:10.1016/j.metabol.2015.04.010 · Cited by 96
“It is possible that HFD induces insulin resistance [30], which then reduces glucose transporter 4 expression in the heart.”
Diet-induced obesity alters protein synthesis: tissue-specific effects in fasted versus fed mice
Anderson, S. R., Gilge, D. A., Steiber, A. L., & Previs, S. F. (2008) · Metabolism · doi:10.1016/j.metabol.2007.10.009 · Cited by 89
“For example, Park et al [31] demonstrated that high-fat feeding to C57BL/6J mice resulted in insulin resistance in liver (and skeletal muscle and adipose tissue) after only 3 weeks of dietary intervention.”
BackgroundOsteopontin Is Required for the Early Onset of High Fat Diet-Induced Insulin Resistance in Mice
Chapman, J., Miles, P. D. G., Ofrecio, J. M., Neels, J. G., Yu, J. G., Resnik, J. L., Wilkes, J. J., Talukdar, S., Thapar, D., Johnson, K., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013959 · Cited by 93
“After prolonged HFD (16–20 weeks), these phenotypes are much more pronounced and accompanied by other severe metabolic dysregulation including dyslipidemia & ectopic triglyceride storage, hypo-adiponectinemia, adipose tissue hypoxia, cell death and remodeling, beta-cell decompensation, mild hyperglycemia, and deterior…”
BackgroundMatyšková, R., Maletı́nská, L., Maixnerová, J., Pirník, Z., Kiss, A., & Železná, B. (2008) · Physiological Research · doi:10.33549/physiolres.931274 · Cited by 86
Cardiac and Metabolic Variables in Obese Dogs
Tropf, M. A., Nelson, O. L., Lee, P. M., & Weng, H. (2017) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.14775 · Cited by 86
Morrison, C. D., Huypens, P., Stewart, L. K., & Gettys, T. W. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.09.005 · Cited by 83
“Consumption of the very high fat (58 kcal%) diet formulation for 2–3 wks after weaning produces a rapid, uniform increase in IR among peripheral tissues [4;5].”
BackgroundRaher, M. J., Thibault, H., Buys, E. S., Kuruppu, D., Shimizu, N., Brownell, A., Blake, S. L., Rieusset, J., Kaneki, M., Dérumeaux, G., et al. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00139.2008 · Cited by 82
Small, L., Brandon, A. E., Turner, N., & Cooney, G. J. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00337.2017 · Cited by 72
From Obesity to Hippocampal Neurodegeneration: Pathogenesis and Non-Pharmacological Interventions
Lee, T. H.-Y., & Yau, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010201 · Cited by 78
TRPM2 Ca2+ channel regulates energy balance and glucose metabolism
Zhang, Z., Zhang, W., Jung, D. Y., Ko, H. J., Lee, Y., Friedline, R. H., Lee, E., Jun, J. Y., Ma, Z., Kim, F., et al. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00239.2011 · Cited by 76
Self-citationFinger, B. C., Dinan, T. G., & Cryan, J. F. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.06.015 · Cited by 76
“Best described in models of diet-induced obesity, prolonged feeding leads to an augmentation of body fat deposition, accompanied by the gradual development of leptin and insulin resistance (Park et al., 2005; Morrison et al., 2009).”
BackgroundZeng, X., Wang, Y., Cantley, J., Iseli, T. J., Molero, J. C., Hegarty, B. D., Kraegen, E. W., Yang, Y., & Ye, J.-M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042115 · Cited by 78
“Chronic HF feeding in rodents is a widely used model of insulin resistance, associated with lipid accumulation in muscle and liver [7,32].”
BackgroundGupta, D., Jetton, T. L., LaRock, K., Monga, N., Satish, B., Lausier, J., Peshavaria, M., & Leahy, J. L. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.781047 · Cited by 76
“(54) identified hyperinsulinemia, systemic insulin resistance, adipose inflammation, and increased hepatic glucose production after just 3 days of the same HF formula that was used in this study.”
BackgroundMethodMicroRNA-194 Modulates Glucose Metabolism and Its Skeletal Muscle Expression Is Reduced in Diabetes
Latouche, C., Natoli, A., Reddy-Luthmoodoo, M., Heywood, S. E., Armitage, J. A., & Kingwell, B. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0155108 · Cited by 73
Puerarin improves insulin resistance and modulates adipokine expression in rats fed a high-fat diet
Zhang, W., Liu, C., Wang, P., Sun, S.-Y., Su, W., Zhang, H., Li, X., & Yang, S. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.09.054 · Cited by 72
Hernández‐Mijares, A., Rocha, M., Rovira‐Llopis, S., Bañuls, C., Bellod, L., de Pablo, C., Álvarez, Á., Torres, I. R., Solá-Izquierdo, E., & Víctor, V. M. (2013) · Diabetes Care · doi:10.2337/dc12-1224 · Cited by 78
“In experimental models of obesity and diabetes, insulin resistance is commonly detected in tissues such as those in the heart (7).”
BackgroundGlucose transporters in cardiovascular system in health and disease
Bertrand, L., Auquier, J., Renguet, E., Angé, M., Cumps, J., Horman, S., & Beauloye, C. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02444-8 · Cited by 72
Ghrelin Enhances in Vivo Skeletal Muscle But Not Liver AKT Signaling in Rats
Barazzoni, R., Zanetti, M., Cattin, M. R., Visintin, L., Vinci, P., Cattin, L., Stebel, M., & Guarnieri, G. (2007) · Obesity · doi:10.1038/oby.2007.313 · Cited by 72
“Reduced insulin signaling occurs under insulin-stimulated rather than basal conditions, and it is not associated with rapid onset of hyperglycemia (36,42).”
BackgroundResultHenagan, T. M., Lenard, N. R., Gettys, T. W., & Stewart, L. K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089365 · Cited by 74
“HFD decreases PGC1a expression in several tissues, including skeletal muscle [6,13], which is one of the primary tissues to exhibit IR during the onset of type 2 diabetes [5,30].”
Hong, E., Jung, D. Y., Ko, H. J., Zhang, Z., Ma, Z., Jun, J. Y., Kim, J. H., Sumner, A. D., Vary, T. C., Gardner, T. W., et al. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00256.2007 · Cited by 69
Self-citationWeng, Y.-C., Chuang, S.-T., Lin, Y.-C., Chuang, C.-F., Chi, T.-C., Chiu, H., Kuo, Y., & Su, M. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/984780 · Cited by 70
A family history of type 2 diabetes increases risk factors associated with overfeeding
Samocha‐Bonet, D., Campbell, L. V., Viardot, A., Freund, J., Tam, C. S., Greenfield, J. R., & Heilbronn, L. K. (2010) · Diabetologia · doi:10.1007/s00125-010-1768-y · Cited by 73
“High-fat overfeeding induces insulin resistance in rodent models in as little as 3 weeks [23, 24].”
BackgroundStewart, L. K., Wang, Z., Ribnicky, D., Soileau, J. L., Cefalu, W. T., & Gettys, T. W. (2009) · Diabetologia · doi:10.1007/s00125-008-1252-0 · Cited by 71
“The response pattern is common to rats and mice on very-HF diets, and supports the view that whole-body insulin resistance is the product of uniform progression of insulin resistance among peripheral tissues [3, 4, 31, 32].”
BackgroundDiet-induced obesity causes long QT and reduces transcription of voltage-gated potassium channels
Huang, H., Amin, V., Gurin, M. I., Wan, E. Y., Thorp, E. B., Homma, S., & Morrow, J. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.03.007 · Cited by 70
“Wild type (WT) mice become obese if fed a high-fat diet for 3 months (Sup Fig 1A)[25].”
BackgroundAbdurrachim, D., Čiapaitė, J., Wessels, B., Nabben, M., Luiken, J. J. F. P., Nicolay, K., & Prompers, J. J. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.07.016 · Cited by 70
Interaction of diet and diabetes on cardiovascular function in rats
Marsh, S. A., Dell’Italia, L. J., & Chatham, J. C. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00421.2008 · Cited by 66
“However, the duration of insulin resistance before STZ treatment was clearly relatively short, and there is evidence to suggest that insulin resistance initiates pathways that are subsequently exacerbated by diabetes and may contribute to cardiac dysfunction (36, 48).”
BackgroundFood and Western Disease Health and Nutrition from an Evolutionary Perspective
Lindeberg, S. (2009) · Cited by 64
Guedes, J. A. C., Esteves, J. V. D. C., Morais, M., Zorn, T. M. T., & Furuya, D. T. (2017) · Bone · doi:10.1016/j.bone.2017.11.020 · Cited by 65
Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity
Zhao, L., Fu, Z., Wu, J., Aylor, K. W., Barrett, E. J., Cao, W., & Liu, Z. (2015) · Clinical Science · doi:10.1042/cs20150143 · Cited by 66
Ge, F., Hu, C., Hyodo, E., Arai, K., Zhou, S., Lobdell, H., Walewski, J. L., Homma, S., & Berk, P. D. (2011) · Journal of Obesity · doi:10.1155/2012/205648 · Cited by 64
Influence of dark phase restricted high fat feeding on myocardial adaptation in mice
Tsai, J.-Y., Villegas‐Montoya, C., Boland, B. B., Blasier, Z., Egbejimi, O., Gonzalez, R., Kueht, M., McElfresh, T. A., Brewer, R. A., Chandler, M. P., et al. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.09.010 · Cited by 62
“In rodents, prolonged Western/high fat feeding has often been reported to modestly depress baseline myocardial contractile function [8-12].”
BackgroundInsulin resistance in the liver: Deficiency or excess of insulin?
Bazotte, R. B., Silva, L. G., & Schiavon, F. P. M. (2014) · Cell Cycle · doi:10.4161/15384101.2014.947750 · Cited by 64
OLIVEIRA, E. B. D., de Moura, E. G., Santos-Silva, A. P., Pinheiro, C. R., Lima, N. S., Nogueira-Neto, J. F., Nunes‐Freitas, A. L., Abreu‐Villaça, Y., Passos, M. C. F., & Lisboa, P. C. (2010) · Journal of Endocrinology · doi:10.1677/joe-10-0104 · Cited by 61
“Also, plasma adiponectin levels were normalized to whole-body fat mass (Park et al. 2005).”
Linden, M. A., Pincu, Y., Martin, S. A., Woods, J. A., & Baynard, T. (2014) · Physiological Reports · doi:10.14814/phy2.12071 · Cited by 64
“This tissue-specific insulin resistance may contribute to the overall disease state in type 2 diabetes and can be accompanied by a doubling of fasting insulin concentrations (Park et al. 2005).”
BackgroundImplications of myocardial matrix remodeling by adipokines in obesity-related heart failure
Schram, K., & Sweeney, G. (2008) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2008.10.001 · Cited by 59
“In the more physiologically relevant murine model of diet-induced obesity (DIO), elevated leptin levels were detected after 20 weeks of a chronic high-fat diet (Park et al. 2005), and this correlated with reduced”
Background
Metadata
- Authors
- Park, S.-Y., Cho, Y.-R., Kim, H.-J., Higashimori, T., Danton, C., Lee, M.-K., Dey, A., Rothermel, B., Kim, Y.-B., Kalinowski, A., Russell, K. S., & Kim, J. K.
- Affiliations
- Yale University (US)
- The University of Texas Southwestern Medical Center (US)
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-12-01
- Volume
- 54
- Issue
- 12
- Pages
- 3530-3540
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2144568374
- Cited by
- 286
- References
- 58
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 14 · 2020: 14 · 2019: 11 · 2018: 8 · 2017: 16 · 2016: 17 · 2015: 24 · 2014: 21 · 2013: 29 · 2012: 20
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- Robert E. Leet and Clara Guthrie Patterson Trust
- American Heart Association
- National Institutes of Health (5r01hl072016-10)
- U.S. Public Health Service
- National Heart, Lung, and Blood Institute (R01 HL-072016)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, U24DK59635, U24DK059635, U24-DK59635-P, P30DK045735)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- insulin resistance, cardiac insulin resistance, high-fat diet, obesity, type 2 diabetes, cardiac glucose metabolism, Akt signaling, GLUT4, skeletal muscle insulin resistance, hepatic insulin resistance, adipose tissue insulin resistance, resistin, leptin, adiponectin, intramuscular fat, intrahepatic triglyceride, cardiac dysfunction, C57BL/6 mice
- MeSH terms
- Adipose Tissue, Animals, Animal Feed, Blood Glucose, Dietary Fats, Glucose, Heart, Heart Diseases, Insulin, Insulin Resistance, Mice, Inbred C57BL, Myocardium, Organ Specificity, Glucose Clamp Technique, Mice
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