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Leptin selectively decreases visceral adiposity and enhances insulin action
Open accessAbstract
Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality. Leptin, a fat-derived protein encoded by the ob gene, has been postulated to be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeostasis. Here, we provide evidence for specific effects of leptin on fat distribution and in vivo insulin action. Leptin (LEP) or vehicle (CON) was administered by osmotic minipumps for 8 d to pair-fed adult rats. During the 8 d of the study, body weight and total fat mass decreased similarly in LEP and in CON. However, while moderate calorie restriction (CON) resulted in similar decreases in whole body (by 20%) and visceral (by 21%) fat, leptin administration led to a specific and marked decrease (by 62%) in visceral adiposity. During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake. Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partitioning of metabolic fluxes, which are likely to represent a defense against excessive storage of energy in adipose depots. These studies demonstrate novel actions of circulating leptin in the regulation of fat distribution, insulin action, and hepatic gene expression and suggest that it may play a role in the pathophysiology of abdominal obesity and insulin resistance.
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“High leptin levels may lead to IR in nonobese PCOS patients by promoting the following events: (i) inhibition of phosphoenolpyruvate carboxykinase, causing decreased hepatic glucose oxidation and increased hepatic glycogen reserve; (ii) fat deposition in skeletal muscle cells; (iii) fat breakdown and free fatty acid production; and (iv) direct inhibition of basal insulin secretion and glucose-stim”
From Circulating Adipokine Levels in Nonobese Women with Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis (2021) · cites this paper as [34]
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Items 101–200 of 336
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“Additionally, high leptin levels inhibit proinsulin mRNA expression, involving decreased transcription activity of the insulin gene promoter and decreased phosphorylation of insulin receptors in peripheral tissues (33, 34).”
Backgroundde França, S. A., dos Santos, M. P., Garófalo, M. A. R., Navegantes, L. C. C., Kettelhut, Í. D. C., Lopes, C. F., & Kawashita, N. H. (2009) · Nutrition · doi:10.1016/j.nut.2009.03.011 · Cited by 79
“At the same time, leptin inhibits insulin secretion and increases its peripheral sensitivity [30,31], explaining the fact that LP animals in our experiments showed normal postprandial glycemic levels, with a lower serum insulin concentration and a reduction in fasting glycemia without changes in insulin levels [30].”
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“Our conclusion of both the insulin-independent and insulin-dependent effect of leptin on hepatic 11 -HSD1 is consistent with several studies suggesting that insulin antagonizes the actions of leptin and that some effects of leptin in peripheral tissues can be partly obtained in the setting of reduced circulating insul…”
ResultAdipose tissues as endocrine target organs
Lanthier, N., & Leclercq, I. A. (2014) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2014.07.002 · Cited by 82
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“Leptin reduces intracellular accumulation of lipids in liver, muscle, and in the pancreatic islet (1, 8, 13, 20).”
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Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents
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“Treatment modalities that limit adiposity such as CR, leptin treatment or removal of visceral fat have been shown to improve insulin action in rat models (Barzilai et al., 1997, 1998, 1999).”
Yaspelkis, B. B., Davis, J. R., Saberi, M., Smith, T. L., Jazayeri, R., Singh, M. K., Fernández, V. G., Trevino, B., Chinookoswong, N., Wang, J., et al. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.1.e130 · Cited by 78
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InfluentialSolano, J. M., & Jacobson, L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.4.e708 · Cited by 75
“Because glucocorticoids and leptin affect insulin sensitivity (4, 30, 34), which, in turn, may influence appetite and metabolic regulation (8, 39), we have also examined the effects of combined hormone treatment on plasma insulin levels.”
BackgroundEndurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle
Steinberg, G. R., Smith, A. C., Wormald, S., Malenfant, P., Collier, C., & Dyck, D. J. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00302.2003 · Cited by 73
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“, 1995) and improve insulin-stimulated glucose disposal in normal muscle (Barzilai et al., 1997; Sivitz et al., 1997; Wang et al., 1999; Yaspelkis et al., 1999).”
BackgroundDietary (n-3) Polyunsaturated Fatty Acids Up-Regulate Plasma Leptin in Insulin-Resistant Rats
Peyron-Caso, É., Taverna, M. J., Véronèse, A., Pacher, N., Slama, G., Rizkalla, S. W., & Guerre-Millo, M. (2002) · Journal of Nutrition · doi:10.1093/jn/132.8.2235 · Cited by 71
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Resistance to leptin action is the major determinant of hepatic triglyceride accumulation in vivo
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“production by redistributing hepatic Glc fluxes (20).”
BackgroundMethodDecrease in Glucose-Stimulated Insulin Secretion With Aging Is Independent of Insulin Action
Muzumdar, R. H., Ma, X., Atzmon, G., Vuguin, P. M., Yang, X., & Barzilai, N. (2004) · Diabetes · doi:10.2337/diabetes.53.2.441 · Cited by 71
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Advances in the Understanding and Treatment of Nonalcoholic Fatty Liver Disease
Harrison, S. A., & Bisceglie, A. M. D. (2003) · Drugs · doi:10.2165/00003495-200363220-00001 · Cited by 69
Relationship between serum leptin and insulin resistance among obese Nigerian women
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Interaction between Aging and Syndrome X: New Insights on the Pathophysiology of Fat Distribution
Barzilai, N., & Gupta, G. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07785.x · Cited by 67
Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms
Muzumdar, R. H., Ma, X., Yang, X., Atzmon, G., Bernstein, J., Karkanias, G. B., & Barzilai, N. (2003) · The FASEB Journal · doi:10.1096/fj.02-0991fje · Cited by 69
“These leptin infusions was designed based on previous experience (8, 18, 19) to achieve physiological plasma leptin levels of ~20 ng/ml and ~320 ng/ml, respectively.”
MethodResultLeptin treatment prevents type I diabetic marrow adiposity but not bone loss in mice
Motyl, K. J., & McCabe, L. R. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21608 · Cited by 63
“This is likely due to leptin treatment effectively reducing insulin levels in non-diabetic mice (Table 1), and enhancing insulin sensitivity, thereby reducing glucose-stimulated insulin release from the pancreas, as previously shown (Barzilai et al., 1997; Sivitz et al., 1997; Wang et al., 1999).”
ResultBalaskó, M., Soós, S., Székely, M., & Pétervári, E. (2014) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2014.08.006 · Cited by 64
Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action
Barzilai, N., She, L., Liu, L., Wang, J., Hu, M., Vuguin, P. M., & Rossetti, L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.2.e291 · Cited by 63
“We have recently reported that the administration of the ‘‘anorectic’’ fat-derived hormone, leptin, to moderately obese rats leads to a selective decrease in intra-abdominal adiposity and to marked improvements in both hepatic and peripheral insulin action (7).”
BackgroundMethodInfluentialSuzuki, R., Tobe, K., Aoyama, M., Inoue, A., Sakamoto, K. Q., Yamauchi, T., Kamon, J., Kubota, N., Terauchi, Y., Yoshimatsu, H., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311956200 · Cited by 59
Mechanisms regulating leptin production: implications for control of energy balance
Havel, P. J. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/70.3.305 · Cited by 60
“In addition, ongoing studies are clarifying the central nervous system (CNS) mechanisms by which leptin exerts its effects on energy balance (4) as well as suggesting important actions for leptin in regulating peripheral metabolic fluxes (5).”
BackgroundRouru, J., Cusin, I., Zakrzewska, K. E., Jeanrenaud, B., & Rohner‐Jeanrenaud, F. (1999) · Endocrinology · doi:10.1210/endo.140.8.6890 · Cited by 64
Rethinking leptin and insulin action: Therapeutic opportunities for diabetes
Yıldız, B. O., & Haznedaroğlu, İ. C. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.09.013 · Cited by 58
Long-term effects of diet on leptin, energy intake, and activity in a model of diet-induced obesity
Roberts, C. K., Berger, J. J., & Barnard, R. J. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00224.2002 · Cited by 58
“Leptin has been documented to regulate food intake, body temperature, energy expenditure (38), insulin action (6), and blood pressure (49), and thus it might play a role in the metabolic syndrome.”
BackgroundSurgical removal of visceral adipose tissue: Effects on insulin action
Gabriely, I., & Barzilai, N. (2003) · Current Diabetes Reports · doi:10.1007/s11892-003-0064-3 · Cited by 58
Yaspelkis, B. B., Ansari, L., Ramey, E. L., Holland, G. J., & Loy, S. F. (1999) · Metabolism · doi:10.1016/s0026-0495(99)90070-7 · Cited by 57
In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus
Benomar, Y., Wetzler, S., Larue‐Achagiotis, C., Djiane, J., Tomé, D., & Taouis, M. (2005) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2005.07.003 · Cited by 57
Hyperglycemia modulates angiotensinogen gene expression
Gabriely, I., Yang, X. M., Cases, J. A., Xiao, H., Rossetti, L., & Barzilai, N. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.3.r795 · Cited by 57
Kim, D., Jeong, Y., Kwon, J., Moon, K., Kim, H.-J., Jeon, S.-M., Lee, M., Park, Y. B., & Choi, M. (2008) · Journal of Medicinal Food · doi:10.1089/jmf.2007.560 · Cited by 56
“44 This suggests that the low leptin level of those with type 2 diabetes can increase insulin resistance and worsen the diabetic condition.”
Leptin Increases Hepatic Insulin Sensitivity and Protein Tyrosine Phosphatase 1B Expression
Lam, N. T., Lewis, J. T., Cheung, A. T., Luk, C. T., Tse, J. W., Wang, J., Bryer‐Ash, M., Kolls, J. K., & Kieffer, T. J. (2004) · Molecular Endocrinology · doi:10.1210/me.2002-0193 · Cited by 53
Insulin resistance of muscle glucose transport in male and female rats fed a high-sucrose diet
Kim, J., Nolte, L. A., Hansen, P. A., Han, D., Kawanaka, K., & Holloszy, J. O. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.3.r665 · Cited by 55
“(2) showing that leptin administration selectively decreases visceral adiposity and markedly enhances insulin-stimulated glucose uptake during a euglycemic, hyperinsulinemic clamp.”
BackgroundEnhanced activation of a “nutrient‐sensing” pathway with age contributes to insulin resistance
Einstein, F. H., Fishman, S., Bauman, J., Thompson, R. F., Huffman, D. M., Atzmon, G., Barzilai, N., & Muzumdar, R. H. (2008) · The FASEB Journal · doi:10.1096/fj.08-109041 · Cited by 52
Shi, Z. Q., Nelson, A. G., Whitcomb, L., Wang, J., & Cohen, A. M. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90336-5 · Cited by 52
da Silva, A. A., Tallam, L. S., Liu, J., & Hall, J. E. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00187.2006 · Cited by 51
“decreases plasma insulin levels in normal rats (2, 4, 29, 34) and”
BackgroundLeptin activates Stat3, Stat1 and AP-1 in mouse adipose tissue
Bendinelli, P., Maroni, P., Giraldi, F. P., & Piccoletti, R. (2000) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(00)00313-0 · Cited by 54
Gürsoy, A. Y., Kiseli, M., & Çağlar, G. S. (2015) · Climacteric · doi:10.3109/13697137.2015.1052393 · Cited by 50
Araújo, R. L., Andrade, B. M., da Silva, M. L., Ferreira, A. C. F., & de Carvalho, D. P. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90869.2008 · Cited by 52
“5 g g body wt 1 day 1 to 10 g/day) significantly reduced food intake (33%-50%) and, as a consequence, was able to determine body and fat mass loss (7, 15, 43).”
BackgroundSleep-Disordered Breathing and Metabolic Effects: Evidence from Animal Models
Jun, J. C., & Polotsky, V. Y. (2007) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2007.03.009 · Cited by 52
“In addition, HIF-1 up-regulates leptin [95], which also increases insulin sensitivity [96;97].”
BackgroundMuñoz, M. C., Giani, J. F., Dominici, F. P., Turyn, D., & Toblli, J. E. (2009) · Journal of Hypertension · doi:10.1097/hjh.0b013e3283310e1b · Cited by 49
Peng, X., Ju, S., Fang, F., Wang, Y., Fang, K., Cui, X., Liu, C., Li, P., Mao, H. Z., & Teng, G. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00401.2012 · Cited by 49
“Leptin has a great impact on metabolic activities based on the visceral or subcutaneous regions of fat distribution that contribute to the whole body weight (4, 16, 38).”
BackgroundRoss, R., Rossetti, L., Lam, T. K. T., & Schwartz, G. J. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00190.2010 · Cited by 49
“0 Ci/min; PerkinElmer) was administered intravenously to determine the contribution of gluconeogenesis to the pool of hepatic glucose 6-phosphate (2).”
MethodEarly intracellular events induced by in vivo leptin treatment in mouse skeletal muscle
Maroni, P., Bendinelli, P., & Piccoletti, R. (2003) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00427-6 · Cited by 48
Present and future therapeutic strategies in non-alcoholic fatty liver disease
Calamita, G., & Portincasa, P. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.9.1231 · Cited by 47
“An interesting human model is lipodystrophy: a disorder of peripheral fat deposition, characterised by nearly absent peripheral fat, severe hepatic steatosis and diabetes, conditions almost completely reversible with leptin administration [49] .”
BackgroundSingh, M. K., Krisan, A. D., Crain, A., Collins, D. E., & Yaspelkis, B. B. (2003) · Metabolism · doi:10.1016/s0026-0495(03)00158-6 · Cited by 47
“We then used our high-fat–fed rodent model8,15 in conjunction with leptin treatment, to (1) assess the effects of a high-fat diet on components of the insulin-signaling cascade and glucose transport effector system and (2) determine if improvements in skeletal muscle insulin resistance induced by chronic leptin treatm…”
MethodLeptin, Obesity, and Obstructive Sleep Apnea
Marik, P. E. (2000) · CHEST Journal · doi:10.1378/chest.118.3.569 · Cited by 48
Leptin, skeletal muscle lipids, and lipid-induced insulin resistance
Dubé, J. J., Bhatt, B. A., Dedousis, N., Bonen, A., & O'Doherty, R. M. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00133.2007 · Cited by 47
“Our group (11) and others (3, 43, 54, 60, 61) have previously demonstrated that leptin increases insulin-stimulated glucose uptake into skeletal muscle.”
BackgroundMethodInfluentialNutrient Modulation of Cellular Insulin Action
Patti, M. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07796.x · Cited by 47
Reverchon, M., Ramé, C., Cognié, J., Briant, E., Elis, S., Guillaume, D., & Dupont, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093198 · Cited by 46
“Indeed, unlike resistin, leptin is known to increase insulin sensitivity [43].”
BackgroundŠtrbák, V., Benický, J., Macho, L., Ježová, D., & Nikodémová, M. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90335-3 · Cited by 45
Lempesis, I. G., Tsilingiris, D., Liu, J., & Dalamaga, Μ. (2022) · Metabolism Open · doi:10.1016/j.metop.2022.100208 · Cited by 45
Leptin resistance following over-expression of protein tyrosine phosphatase 1B in liver
Lam, N., Covey, S. D., Lewis, J. T., Oosman, S. N., Webber, T. D., Hsu, E. C., Cheung, A. T., & Kieffer, T. J. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01937 · Cited by 46
“The mechanism by which leptin reduces blood glucose likely involves enhanced glucose uptake by peripheral tissues and inhibition of hepatic glucose production (Barzilai et al. 1997, Kamohara et al. 1997, Rossetti et al. 1997, Chinookoswong et al. 1999, Anderwald et al. 2002).”
BackgroundComparison of Gene Transcription between Subcutaneous and Visceral Adipose Tissue in Chinese Adults
Zha, J., Di, W. J., Zhu, T., Xie, Y., Yu, J., Liu, J., Chen, P., & Ding, G. (2009) · Endocrine Journal · doi:10.1507/endocrj.k09e-091 · Cited by 44
Volpe, S. L., Kobusingye, H. K., Bailur, S., & Stanek, E. J. (2008) · Journal of the American College of Nutrition · doi:10.1080/07315724.2008.10719691 · Cited by 44
Sahu, A., Nguyen, L., & O'Doherty, R. M. (2002) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2002.00856.x · Cited by 45
Counterregulation of insulin by leptin as key component of autonomic regulation of body weight
Borer, K. T. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i5.606 · Cited by 45
Inter-organ Leptin Exchange in Humans
Garibotto, G., Russo, R., Franceschini, R., Robaudo, C., Saffioti, S., Sofia, A., Rolandi, E., Deferrari, G., & BARRECA, T. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8819 · Cited by 42
Leptin and Body Fat in Type 2 Diabetes and Monodrug Therapy
Sivitz, W. I., Wayson, S. M., Bayless, M., Larson, L. F., Sinkey, C. A., Bar, R. S., & Haynes, W. G. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021193 · Cited by 42
Paniagua, J. A., Escandell-Morales, J. M., Gil-Contreras, D., de la Rosa, F. J. B., Romero-Jimenez, M., Gómez-Urbano, A., Sánchez‐López, Á. M., Bellido, E., Poyato, A., Calatayud, B. M., et al. (2014) · Nutrition · doi:10.1016/j.nut.2013.07.017 · Cited by 41
Artificial Neural Networks Based Controller for Glucose Monitoring during Clamp Test
Catalogna, M., Cohen, E., Fishman, S., Halpern, Z., Nevo, U., & Ben‐Jacob, E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044587 · Cited by 41
“All studies were performed as described in previous studies [12,13].”
Cesquini, M., Stoppa, G. R., Prada, P. O., Torsoni, A. S., Romanatto, T., Souza, A. B. D. S., Saad, M. J. A., Velloso, L. A., & Torsoni, M. A. (2008) · Life Sciences · doi:10.1016/j.lfs.2008.04.015 · Cited by 44
“Furthermore, it has been demonstrated that systemic and intracerebroventricular administration of leptin increases sympathetic activity to BATand other peripheral tissues (Collins et al., 1996; Haynes et al., 1997) and increases insulin sensitivity (Barzilai et al., 1997; Shi et al., 1998).”
BackgroundDallongeville, J., Fruchart, J., & Auwerx, J. H. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm9802867 · Cited by 40
Role of leptin in regulating appetite, neuroendocrine function, and bone remodeling
Cohen, M. M. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31099 · Cited by 42
“Exogenously-induced leptin enhances glycemic control [Kamohara et al., 1997; Barzilai et al., 1999; Burcelin et al., 1999].”
BackgroundScapa, E. F., Pocai, A., Wu, M. K., Juárez, R. G., Glenz, L. T., Kanno, K., Li, H. L., Biddinger, S. B., Jelicks, L. A., Rossetti, L., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-105395 · Cited by 39
“As described previously (20), plasma glucose concentrations and specific activity, as well as the specific activities in the liver of phosphoenolpyruvate and UDP-glucose, were measured and used to determine rates of glucose uptake, hepatic glucose production, total glucose output, glucose cycling, gluconeogenesis, and…”
MethodHolness, M. J., & Sugden, M. C. (2001) · Endocrinology · doi:10.1210/endo.142.9.8379 · Cited by 37
Cheng, M., Tsai, T., & Pan, T. (2015) · Food & Function · doi:10.1039/c5fo00531k · Cited by 38
“And for the present study, the total visceral fat mass represents the 158 sum of mesenteric, epididymal, and perinephric fat as Barzilai et al. (1997) showed; 25 159 the subcutaneous fat were the sum of fat around the groin and lumbar; the carcass was 160 defined as the entire shaved rat torso…”
BackgroundBopparaju, S., & Surani, S. (2010) · International Journal of Endocrinology · doi:10.1155/2010/759509 · Cited by 37
“Leptin, IL-6, and inflammatory mediators have also been implicated in the pathogenesis of insulin resistance and other features of metabolic syndrome [97, 98].”
BackgroundVelloso, L. A. (2009) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302009000200006 · Cited by 38
Leptin is involved in gender‐related differences in insulin sensitivity
Fernández‐Real, J. M., Casamitjana, R., & Ricart, W. (1998) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1998.00566.x · Cited by 36
Leptin as a Potential Treatment for Obesity: Progress to Date
Bell-Anderson, K. S., & Bryson, J. M. (2004) · Treatments in Endocrinology · doi:10.2165/00024677-200403010-00002 · Cited by 36
Chronic administration of leptin in Asian Blue Quail
Lõhmus, M., Sundström, L. F., & Silverin, B. (2005) · Journal of Experimental Zoology Part A Comparative Experimental Biology · doi:10.1002/jez.a.240 · Cited by 35
Leptin Deficiency Per Se Dictates Body Composition and Insulin Action in ob/ob Mice
Van Den Hoek, A. M., Teusink, B., Voshol, P. J., Havekes, L. M., Romijn, J. A., & Pijl, H. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01626.x · Cited by 34
Miro, C., Cicatiello, A. G., Nappi, A., Sagliocchi, S., Acampora, L., Restolfer, F., Cuomo, O., de Alteriis, G., Pugliese, G., Torabinejad, S., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.01.025 · Cited by 35
[d-LEU-4]-OB3, a synthetic leptin agonist, improves hyperglycemic control in C57BL/6J ob/ob mice
Grasso, P., Rozhavskaya-Arena, M., Leinung, M. C., & Lee, D. W. (2001) · Regulatory Peptides · doi:10.1016/s0167-0115(01)00274-9 · Cited by 34
Serum Leptin in Patients with Alcoholic Liver Disease
Naveau, S., Perlemuter, G., Chaillet, M., Raynard, B., Balian, A., Beuzen, F., Portier, A., Galanaud, P., Émilie, D., & Chaput, J. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00170.x · Cited by 34
Zhou, Y., & Tan, C. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00171 · Cited by 33
Leptin responses to glucose infusions in obesity-prone rats
Levy, J. R., Lesko, J. M., Krieg, R. J., Adler, R. A., & Stevens, W. D. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.5.e1088 · Cited by 33
“Leptin has been shown to have salutary effects on glucose metabolism (5, 37, 42, 48).”
BackgroundHammond, J. A., Bennett, K. A., Walton, M. J., & Hall, A. J. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00203.2004 · Cited by 32
“Leptin acts peripherally to promote the use of fat as a metabolic fuel and to stimulate adipocyte apoptosis (3, 7).”
BackgroundSex‐dependent Associations of Leptin With Metabolic Syndrome–related Variables: The Stanislas Study
Samara, A., Herbeth, B., Aubert, R., Berrahmoune, H., Fumeron, F., Siest, G., & Visvikis‐Siest, S. (2009) · Obesity · doi:10.1038/oby.2009.156 · Cited by 32
“Leptin exerts complex effects on liver gene expression (13).”
BackgroundPeripheral and central regulation of insulin by the intestine and microbiome
Schertzer, J. D., & Lam, T. K. T. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00547.2020 · Cited by 31
Age‐associated changes of appetite‐regulating peptides
Akimoto, S., & Miyasaka, K. (2010) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2010.00587.x · Cited by 31
Role of leptin in glucose metabolism in type 2 diabetes
Al‐Daghri, N. M., Bartlett, W. A., Jones, A. F., & Kumar, S. (2002) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2002.00194.x · Cited by 31
Metadata
- Authors
- Barzilai, N., Wang, J., Massilon, D., Vuguin, P., Hawkins, M., & Rossetti, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Rossetti, L
- Venue
- Journal of Clinical Investigation
- Published
- 1997-12-15
- Volume
- 100
- Issue
- 12
- Pages
- 3105-3110
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508523
- OpenAlex
- W2152760501
- Cited by
- 335
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2022: 2 · 2021: 7 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 12 · 2014: 10 · 2013: 6 · 2012: 11
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Medical Research Council Canada
- National Institutes of Health
- Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, DK20541, DK-45024)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- leptin, visceral fat, intra-abdominal fat, insulin action, insulin resistance, abdominal obesity, body fat distribution, hepatic glucose production, hepatic glucose uptake, hepatic gene expression, energy homeostasis, caloric restriction, hyperinsulinemia
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Body Weight, Eating, Glucose, Insulin, Liver, Male, Proteins, Recombinant Proteins, Viscera, Gene Expression, Rats, Sprague-Dawley, Leptin, Mice, Rats
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