Elif Arioglu Oral, M.D., Vinaya Simha, M.D., Elaine Ruiz, N.P., Alexa Andewelt, B.S., Ahalya Premkumar, M.D., Peter Snell, Ph.D., Anthony J. Wagner, Ph.D., Alex M. DePaoli, M.D., Marc L. Reitman, M.D., Ph.D., Simeon I. Taylor, M.D., Ph.D., Phillip Gorden, M.D., and Abhimanyu Garg, M.D.
Background The adipocyte hormone leptin is important in regulatingenergy homeostasis. Since severe lipodystrophy is associatedwith leptin deficiency, insulin resistance, hypertriglyceridemia,and hepatic steatosis, we assessed whether leptin replacementwould ameliorate this condition.
Methods Nine female patients (age range, 15 to 42 years; eightwith diabetes mellitus) who had lipodystrophy and serum leptinlevels of less than 4 ng per milliliter (0.32 nmol per milliliter)received recombinant methionyl human leptin (recombinant leptin).Recombinant leptin was administered subcutaneously twice a dayfor four months at escalating doses to achieve low, intermediate,and high physiologic replacement levels of leptin.
Results During treatment with recombinant leptin, the serumleptin level increased from a mean (±SE) of 1.3±0.3ng per milliliter to 11.1±2.5 ng per milliliter (0.1±0.02to 0.9±0.2 nmol per milliliter). The absolute decreasein the glycosylated hemoglobin value was 1.9 percent (95 percentconfidence interval, 1.1 to 2.7 percent; P=0.001) in the eightpatients with diabetes. Four months of therapy decreased averagetriglyceride levels by 60 percent (95 percent confidence interval,43 to 77 percent; P<0.001) and liver volume by an averageof 28 percent (95 percent confidence interval, 20 to 36 percent;P=0.002) in all nine patients and led to the discontinuationof or a large reduction in antidiabetes therapy. Self-reporteddaily caloric intake and the measured resting metabolic ratealso decreased significantly with therapy. Overall, recombinantleptin therapy was well tolerated.
Conclusions Leptin-replacement therapy improved glycemic controland decreased triglyceride levels in patients with lipodystrophyand leptin deficiency. Leptin deficiency contributes to theinsulin resistance and other metabolic abnormalities associatedwith severe lipodystrophy.
Source Information
From the Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases (E.A.O., E.R., A.A., M.L.R., S.I.T., P.G.), and the Clinical Center (A.P.), National Institutes of Health, Bethesda, Md.; the University of Texas Southwestern Medical Center at Dallas, Dallas (V.S., P.S., A.G.); and Amgen, Thousand Oaks, Calif. (A.J.W., A.M.D.).
Address reprint requests to Dr. Oral at the National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes Branch, Bldg. 10, Rm. 8D20, Bethesda, MD 20892-1770, or at elif_arioglu{at}nih.gov.
Karmazyn, M., Purdham, D. M., Rajapurohitam, V., Zeidan, A.
(2008). Signalling mechanisms underlying the metabolic and other effects of adipokines on the heart. Cardiovasc Res
79: 279-286
[Abstract][Full Text]
Misra, A., Alappan, N. K., Vikram, N. K., Goel, K., Gupta, N., Mittal, K., Bhatt, S., Luthra, K.
(2008). Effect of Supervised Progressive Resistance-Exercise Training Protocol on Insulin Sensitivity, Glycemia, Lipids, and Body Composition in Asian Indians With Type 2 Diabetes. Diabetes Care
31: 1282-1287
[Abstract][Full Text]
Koh, K. K., Park, S. M., Quon, M. J.
(2008). Leptin and Cardiovascular Disease: Response to Therapeutic Interventions. Circulation
117: 3238-3249
[Full Text]
Mallewa, J. E., Wilkins, E., Vilar, J., Mallewa, M., Doran, D., Back, D., Pirmohamed, M.
(2008). HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options. J Antimicrob Chemother
0: dkn251v1-13
[Abstract][Full Text]
Roth, J. D., Roland, B. L., Cole, R. L., Trevaskis, J. L., Weyer, C., Koda, J. E., Anderson, C. M., Parkes, D. G., Baron, A. D.
(2008). Leptin responsiveness restored by amylin agonism in diet-induced obesity: Evidence from nonclinical and clinical studies. Proc. Natl. Acad. Sci. USA
105: 7257-7262
[Abstract][Full Text]
Ahima, R. S., Lazar, M. A.
(2008). Adipokines and the Peripheral and Neural Control of Energy Balance. Mol. Endocrinol.
22: 1023-1031
[Abstract][Full Text]
Chehab, F. F.
(2008). Minireview: Obesity and LipOdystrophy--Where Do the Circles Intersect?. Endocrinology
149: 925-934
[Abstract][Full Text]
Park, J. Y., Chong, A. Y., Cochran, E. K., Kleiner, D. E., Haller, M. J., Schatz, D. A., Gorden, P.
(2008). Type 1 Diabetes Associated with Acquired Generalized Lipodystrophy and Insulin Resistance: The Effect of Long-Term Leptin Therapy. J. Clin. Endocrinol. Metab.
93: 26-31
[Abstract][Full Text]
Kosmiski, L. A, Bessesen, D. H, Stotz, S. A, Koeppe, J. R, Horton, T. J
(2007). Short-term overfeeding increases resting energy expenditure in patients with HIV lipodystrophy. Am. J. Clin. Nutr.
86: 1009-1015
[Abstract][Full Text]
Bermudez-Humaran, L. G., Nouaille, S., Zilberfarb, V., Corthier, G., Gruss, A., Langella, P., Issad, T.
(2007). Effects of Intranasal Administration of a Leptin-Secreting Lactococcus lactis Recombinant on Food Intake, Body Weight, and Immune Response of Mice. Appl. Environ. Microbiol.
73: 5300-5307
[Abstract][Full Text]
Beltrand, J., Beregszaszi, M., Chevenne, D., Sebag, G., De Kerdanet, M., Huet, F., Polak, M., Tubiana-Rufi, N., Lacombe, D., De Paoli, A. M., Levy-Marchal, C.
(2007). Metabolic Correction Induced by Leptin Replacement Treatment in Young Children With Berardinelli-Seip Congenital Lipoatrophy. Pediatrics
120: e291-e296
[Abstract][Full Text]
Bray, G. A., Greenway, F. L.
(2007). Pharmacological Treatment of the Overweight Patient. Pharmacol. Rev.
59: 151-184
[Full Text]
Huang, W., Dedousis, N., O'Doherty, R. M.
(2007). Hepatic steatosis and plasma dyslipidemia induced by a high-sucrose diet are corrected by an acute leptin infusion. J. Appl. Physiol.
102: 2260-2265
[Abstract][Full Text]
Chan, J. L., Wong, S. L., Orlova, C., Raciti, P., Mantzoros, C. S.
(2007). Pharmacokinetics of Recombinant Methionyl Human Leptin after Subcutaneous Administration: Variation of Concentration-Dependent Parameters According to Assay. J. Clin. Endocrinol. Metab.
92: 2307-2311
[Abstract][Full Text]
Beckman, J. A., Goldfine, A. B., Dunaif, A., Gerhard-Herman, M., Creager, M. A.
(2007). Endothelial Function Varies According to Insulin Resistance Disease Type. Diabetes Care
30: 1226-1232
[Abstract][Full Text]
Savage, D. B., Petersen, K. F., Shulman, G. I.
(2007). Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance. Physiol. Rev.
87: 507-520
[Abstract][Full Text]
Sutinen, J., Yki-Jarvinen, H.
(2007). Increased resting energy expenditure, fat oxidation, and food intake in patients with highly active antiretroviral therapy-associated lipodystrophy. Am. J. Physiol. Endocrinol. Metab.
292: E687-E692
[Abstract][Full Text]
Ebihara, K., Kusakabe, T., Hirata, M., Masuzaki, H., Miyanaga, F., Kobayashi, N., Tanaka, T., Chusho, H., Miyazawa, T., Hayashi, T., Hosoda, K., Ogawa, Y., DePaoli, A. M., Fukushima, M., Nakao, K.
(2007). Efficacy and Safety of Leptin-Replacement Therapy and Possible Mechanisms of Leptin Actions in Patients with Generalized Lipodystrophy. J. Clin. Endocrinol. Metab.
92: 532-541
[Abstract][Full Text]
Gao, J., Katagiri, H., Ishigaki, Y., Yamada, T., Ogihara, T., Imai, J., Uno, K., Hasegawa, Y., Kanzaki, M., Yamamoto, T. T., Ishibashi, S., Oka, Y.
(2007). Involvement of Apolipoprotein E in Excess Fat Accumulation and Insulin Resistance. Diabetes
56: 24-33
[Abstract][Full Text]
Foster-Schubert, K. E., Cummings, D. E.
(2006). Emerging Therapeutic Strategies for Obesity. Endocr. Rev.
27: 779-793
[Abstract][Full Text]
Ahima, R. S., Qi, Y., Singhal, N. S., Jackson, M. B., Scherer, P. E.
(2006). Brain Adipocytokine Action and Metabolic Regulation. Diabetes
55: S145-S154
[Abstract][Full Text]
CHARMANDARI, E., CHROUSOS, G. P
(2006). Metabolic Syndrome Manifestations in Classic Congenital Adrenal Hyperplasia: Do They Predispose to Atherosclerotic Cardiovascular Disease and Secondary Polycystic Ovary Syndrome?. Ann. N. Y. Acad. Sci.
1083: 37-53
[Abstract][Full Text]
da Silva, A. A., Tallam, L. S., Liu, J., Hall, J. E.
(2006). Chronic antidiabetic and cardiovascular actions of leptin: role of CNS and increased adrenergic activity. Am. J. Physiol. Regul. Integr. Comp. Physiol.
291: R1275-R1282
[Abstract][Full Text]
Yao-Borengasser, A., Rasouli, N., Varma, V., Miles, L. M., Phanavanh, B., Starks, T. N., Phan, J., Spencer, H. J. III, McGehee, R. E. Jr., Reue, K., Kern, P. A.
(2006). Lipin Expression Is Attenuated in Adipose Tissue of Insulin-Resistant Human Subjects and Increases With Peroxisome Proliferator-Activated Receptor {gamma} Activation.. Diabetes
55: 2811-2818
[Abstract][Full Text]
Semple, R. K., Soos, M. A., Luan, J., Mitchell, C. S., Wilson, J. C., Gurnell, M., Cochran, E. K., Gorden, P., Chatterjee, V. K. K., Wareham, N. J., O'Rahilly, S.
(2006). Elevated Plasma Adiponectin in Humans with Genetically Defective Insulin Receptors. J. Clin. Endocrinol. Metab.
91: 3219-3223
[Abstract][Full Text]
Lee, J. H., Chan, J. L., Sourlas, E., Raptopoulos, V., Mantzoros, C. S.
(2006). Recombinant Methionyl Human Leptin Therapy in Replacement Doses Improves Insulin Resistance and Metabolic Profile in Patients with Lipoatrophy and Metabolic Syndrome Induced by the Highly Active Antiretroviral Therapy. J. Clin. Endocrinol. Metab.
91: 2605-2611
[Abstract][Full Text]
Utzschneider, K. M., Trence, D. L.
(2006). Effectiveness of Gastric Bypass Surgery in a Patient With Familial Partial Lipodystrophy.. Diabetes Care
29: 1380-1382
[Full Text]
Poirier, H., Shapiro, J. S., Kim, R. J., Lazar, M. A.
(2006). Nutritional Supplementation With trans-10, cis-12-Conjugated Linoleic Acid Induces Inflammation of White Adipose Tissue. Diabetes
55: 1634-1641
[Abstract][Full Text]
Gale, S. E., Frolov, A., Han, X., Bickel, P. E., Cao, L., Bowcock, A., Schaffer, J. E., Ory, D. S.
(2006). A Regulatory Role for 1-Acylglycerol-3-phosphate-O-acyltransferase 2 in Adipocyte Differentiation. J. Biol. Chem.
281: 11082-11089
[Abstract][Full Text]
Desvergne, B., Michalik, L., Wahli, W.
(2006). Transcriptional Regulation of Metabolism. Physiol. Rev.
86: 465-514
[Abstract][Full Text]
Durham, H. A., Truett, G. E.
(2006). Development of insulin resistance and hyperphagia in Zucker fatty rats. Am. J. Physiol. Regul. Integr. Comp. Physiol.
290: R652-R658
[Abstract][Full Text]
Greenberg, A. S, Obin, M. S
(2006). Obesity and the role of adipose tissue in inflammation and metabolism. Am. J. Clin. Nutr.
83: 461S-465S
[Abstract][Full Text]
Oral, E. A., Javor, E. D., Ding, L., Uzel, G., Cochran, E. K., Young, J. R., DePaoli, A. M., Holland, S. M., Gorden, P.
(2006). Leptin Replacement Therapy Modulates Circulating Lymphocyte Subsets and Cytokine Responsiveness in Severe Lipodystrophy. J. Clin. Endocrinol. Metab.
91: 621-628
[Abstract][Full Text]
Lofgren, P., Andersson, I., Adolfsson, B., Leijonhufvud, B.-M., Hertel, K., Hoffstedt, J., Arner, P.
(2005). Long-Term Prospective and Controlled Studies Demonstrate Adipose Tissue Hypercellularity and Relative Leptin Deficiency in the Postobese State. J. Clin. Endocrinol. Metab.
90: 6207-6213
[Abstract][Full Text]
Toyoshima, Y., Gavrilova, O., Yakar, S., Jou, W., Pack, S., Asghar, Z., Wheeler, M. B., LeRoith, D.
(2005). Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes. Endocrinology
146: 4024-4035
[Abstract][Full Text]
Hegele, R. A., Pollex, R. L.
(2005). Genetic and physiological insights into the metabolic syndrome. Am. J. Physiol. Regul. Integr. Comp. Physiol.
289: R663-R669
[Abstract][Full Text]
Tanaka, T., Hidaka, S., Masuzaki, H., Yasue, S., Minokoshi, Y., Ebihara, K., Chusho, H., Ogawa, Y., Toyoda, T., Sato, K., Miyanaga, F., Fujimoto, M., Tomita, T., Kusakabe, T., Kobayashi, N., Tanioka, H., Hayashi, T., Hosoda, K., Yoshimatsu, H., Sakata, T., Nakao, K.
(2005). Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation Parallels Metabolic Phenotype in Leptin Transgenic Mice Under Dietary Modification. Diabetes
54: 2365-2374
[Abstract][Full Text]
Klebanov, S., Astle, C. M, DeSimone, O., Ablamunits, V., Harrison, D. E
(2005). Adipose tissue transplantation protects ob/ob mice from obesity, normalizes insulin sensitivity and restores fertility. J Endocrinol
186: 203-211
[Abstract][Full Text]
Milinkovic, A., Martinez, E.
(2005). Current perspectives on HIV-associated lipodystrophy syndrome. J Antimicrob Chemother
56: 6-9
[Abstract][Full Text]
Javor, E. D., Cochran, E. K., Musso, C., Young, J. R., DePaoli, A. M., Gorden, P.
(2005). Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy. Diabetes
54: 1994-2002
[Abstract][Full Text]
Unger, R. H.
(2005). Hyperleptinemia: Protecting the Heart From Lipid Overload. Hypertension
45: 1031-1034
[Abstract][Full Text]
Yu, Y.-H., Ginsberg, H. N.
(2005). Adipocyte Signaling and Lipid Homeostasis: Sequelae of Insulin-Resistant Adipose Tissue. Circ. Res.
96: 1042-1052
[Abstract][Full Text]
Cochran, E., Musso, C., Gorden, P.
(2005). The Use of U-500 in Patients With Extreme Insulin Resistance. Diabetes Care
28: 1240-1244
[Full Text]
Shea, S. A., Hilton, M. F., Orlova, C., Ayers, R. T., Mantzoros, C. S.
(2005). Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans. J. Clin. Endocrinol. Metab.
90: 2537-2544
[Abstract][Full Text]
Sennello, J. A., Fayad, R., Morris, A. M., Eckel, R. H., Asilmaz, E., Montez, J., Friedman, J. M., Dinarello, C. A., Fantuzzi, G.
(2005). Regulation of T Cell-Mediated Hepatic Inflammation by Adiponectin and Leptin. Endocrinology
146: 2157-2164
[Abstract][Full Text]
Rasouli, N., Raue, U., Miles, L. M., Lu, T., Di Gregorio, G. B., Elbein, S. C., Kern, P. A.
(2005). Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue. Am. J. Physiol. Endocrinol. Metab.
288: E930-E934
[Abstract][Full Text]
Savage, D. B., Petersen, K. F., Shulman, G. I.
(2005). Mechanisms of Insulin Resistance in Humans and Possible Links With Inflammation. Hypertension
45: 828-833
[Abstract][Full Text]
Goodpaster, B. H., Krishnaswami, S., Harris, T. B., Katsiaras, A., Kritchevsky, S. B., Simonsick, E. M., Nevitt, M., Holvoet, P., Newman, A. B.
(2005). Obesity, Regional Body Fat Distribution, and the Metabolic Syndrome in Older Men and Women. Arch Intern Med
165: 777-783
[Abstract][Full Text]
Svensson, J., Herlitz, H., Lundberg, P.-A., Johannsson, G.
(2005). Adiponectin, Leptin, and Erythrocyte Sodium/Lithium Countertransport Activity, But Not Resistin, Are Related to Glucose Metabolism in Growth Hormone-Deficient Adults. J. Clin. Endocrinol. Metab.
90: 2290-2296
[Abstract][Full Text]
Chan, J. L., Bullen, J., Stoyneva, V., DePaoli, A. M., Addy, C., Mantzoros, C. S.
(2005). Recombinant Methionyl Human Leptin Administration to Achieve High Physiologic or Pharmacologic Leptin Levels Does Not Alter Circulating Inflammatory Marker Levels in Humans with Leptin Sufficiency or Excess. J. Clin. Endocrinol. Metab.
90: 1618-1624
[Abstract][Full Text]
Savage, D. B., Murgatroyd, P. R., Chatterjee, V. K., O'Rahilly, S.
(2005). Energy Expenditure and Adaptive Responses to an Acute Hypercaloric Fat Load in Humans with Lipodystrophy. J. Clin. Endocrinol. Metab.
90: 1446-1452
[Abstract][Full Text]
Lazar, M. A.
(2005). How Obesity Causes Diabetes: Not a Tall Tale. Science
307: 373-375
[Abstract][Full Text]
Schwartz, M. W., Porte, D. Jr.
(2005). Diabetes, Obesity, and the Brain. Science
307: 375-379
[Abstract][Full Text]
Lee, Y., Naseem, R. H., Duplomb, L., Park, B.-H., Garry, D. J., Richardson, J. A., Schaffer, J. E., Unger, R. H.
(2004). Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice. Proc. Natl. Acad. Sci. USA
101: 13624-13629
[Abstract][Full Text]
Ahima, R., Osei, S. Y.
(2004). Leptin and Appetite Control in Lipodystrophy. J. Clin. Endocrinol. Metab.
89: 4254-4257
[Full Text]
McDuffie, J. R., Riggs, P. A., Calis, K. A., Freedman, R. J., Oral, E. A., DePaoli, A. M., Yanovski, J. A.
(2004). Effects of Exogenous Leptin on Satiety and Satiation in Patients with Lipodystrophy and Leptin Insufficiency. J. Clin. Endocrinol. Metab.
89: 4258-4263
[Abstract][Full Text]
Steinberg, G. R., Smith, A. C., van Denderen, B. J. W., Chen, Z., Murthy, S., Campbell, D. J., Heigenhauser, G. J. F., Dyck, D. J., Kemp, B. E.
(2004). AMP-Activated Protein Kinase Is Not Down-Regulated in Human Skeletal Muscle of Obese Females. J. Clin. Endocrinol. Metab.
89: 4575-4580
[Abstract][Full Text]
Cohen, P., Friedman, J. M.
(2004). Leptin and the Control of Metabolism: Role for Stearoyl-CoA Desaturase-1 (SCD-1). J. Nutr.
134: 2455S-2463S
[Abstract][Full Text]
Meier, U., Gressner, A. M.
(2004). Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin. Clin. Chem.
50: 1511-1525
[Abstract][Full Text]
Ebihara, K., Masuzaki, H., Nakao, K.
(2004). Long-Term Leptin-Replacement Therapy for Lipoatrophic Diabetes. NEJM
351: 615-616
[Full Text]
Javor, E. D., Moran, S. A., Young, J. R., Cochran, E. K., DePaoli, A. M., Oral, E. A., Turman, M. A., Blackett, P. R., Savage, D. B., O'Rahilly, S., Balow, J. E., Gorden, P.
(2004). Proteinuric Nephropathy in Acquired and Congenital Generalized Lipodystrophy: Baseline Characteristics and Course during Recombinant Leptin Therapy. J. Clin. Endocrinol. Metab.
89: 3199-3207
[Abstract][Full Text]
Koutkia, P., Canavan, B., Breu, J., Johnson, M. L, Depaoli, A., Grinspoon, S. K
(2004). Relation of leptin pulse dynamics to fat distribution in HIV-infected patients. Am. J. Clin. Nutr.
79: 1103-1109
[Abstract][Full Text]
Wong, S. L., DePaoli, A. M., Lee, J. H., Mantzoros, C. S.
(2004). Leptin Hormonal Kinetics in the Fed State: Effects of Adiposity, Age, and Gender on Endogenous Leptin Production and Clearance Rates. J. Clin. Endocrinol. Metab.
89: 2672-2677
[Abstract][Full Text]
Banks, W. A., Coon, A. B., Robinson, S. M., Moinuddin, A., Shultz, J. M., Nakaoke, R., Morley, J. E.
(2004). Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier. Diabetes
53: 1253-1260
[Abstract][Full Text]
Cochran, E., Young, J. R., Sebring, N., DePaoli, A., Oral, E. A., Gorden, P.
(2004). Efficacy of Recombinant Methionyl Human Leptin Therapy for the Extreme Insulin Resistance of the Rabson-Mendenhall Syndrome. J. Clin. Endocrinol. Metab.
89: 1548-1554
[Abstract][Full Text]
Popovic, V., Djurovic, M., Cetkovic, A., Vojvodic, D., Pekic, S., Spremovic, S., Petakov, M., Damjanovic, S., Milic, N., Dieguez, C., Casanueva, F. F.
(2004). Inhibin B: A Potential Marker of Gonadal Activity in Patients with Anorexia Nervosa during Weight Recovery. J. Clin. Endocrinol. Metab.
89: 1838-1843
[Abstract][Full Text]
Haluzik, M., Gavrilova, O., LeRoith, D.
(2004). Peroxisome Proliferator-Activated Receptor-{alpha} Deficiency Does Not Alter Insulin Sensitivity in Mice Maintained on Regular or High-Fat Diet: Hyperinsulinemic-Euglycemic Clamp Studies. Endocrinology
145: 1662-1667
[Abstract][Full Text]
Licinio, J., Caglayan, S., Ozata, M., Yildiz, B. O., de Miranda, P. B., O'Kirwan, F., Whitby, R., Liang, L., Cohen, P., Bhasin, S., Krauss, R. M., Veldhuis, J. D., Wagner, A. J., DePaoli, A. M., McCann, S. M., Wong, M.-L.
(2004). Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc. Natl. Acad. Sci. USA
101: 4531-4536
[Abstract][Full Text]
Garg, A.
(2004). Acquired and Inherited Lipodystrophies. NEJM
350: 1220-1234
[Full Text]
Benavides, S., Nahata, M. C
(2004). Pharmacologic Therapy for HIV-Associated Lipodystrophy. The Annals of Pharmacotherapy
38: 448-457
[Abstract][Full Text]
Bays, H., Mandarino, L., DeFronzo, R. A.
(2004). Role of the Adipocyte, Free Fatty Acids, and Ectopic Fat in Pathogenesis of Type 2 Diabetes Mellitus: Peroxisomal Proliferator-Activated Receptor Agonists Provide a Rational Therapeutic Approach. J. Clin. Endocrinol. Metab.
89: 463-478
[Full Text]
Snijder, M. B., Dekker, J. M., Visser, M., Bouter, L. M., Stehouwer, C. D.A., Yudkin, J. S., Heine, R. J., Nijpels, G., Seidell, J. C.
(2004). Trunk Fat and Leg Fat Have Independent and Opposite Associations With Fasting and Postload Glucose Levels: The Hoorn Study. Diabetes Care
27: 372-377
[Abstract][Full Text]
Havel, P. J.
(2004). Update on Adipocyte Hormones: Regulation of Energy Balance and Carbohydrate/Lipid Metabolism. Diabetes
53: S143-151
[Abstract][Full Text]
Steinberg, G. R., Smith, A. C., Wormald, S., Malenfant, P., Collier, C., Dyck, D. J.
(2004). Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle. Am. J. Physiol. Endocrinol. Metab.
286: E57-E63
[Abstract][Full Text]
Gavrila, A., Chan, J. L., Yiannakouris, N., Kontogianni, M., Miller, L. C., Orlova, C., Mantzoros, C. S.
(2003). Serum Adiponectin Levels Are Inversely Associated with Overall and Central Fat Distribution but Are Not Directly Regulated by Acute Fasting or Leptin Administration in Humans: Cross-Sectional and Interventional Studies. J. Clin. Endocrinol. Metab.
88: 4823-4831
[Abstract][Full Text]
Rajala, M. W., Scherer, P. E.
(2003). Minireview: The Adipocyte--At the Crossroads of Energy Homeostasis, Inflammation, and Atherosclerosis. Endocrinology
144: 3765-3773
[Abstract][Full Text]
Couturier, C., Jockers, R.
(2003). Activation of the Leptin Receptor by a Ligand-induced Conformational Change of Constitutive Receptor Dimers. J. Biol. Chem.
278: 26604-26611
[Abstract][Full Text]
Owen, K. R., Stride, A., Ellard, S., Hattersley, A. T.
(2003). Etiological Investigation of Diabetes in Young Adults Presenting With Apparent Type 2 Diabetes. Diabetes Care
26: 2088-2093
[Abstract][Full Text]
Bloomgarden, Z. T.
(2003). Fat Metabolism and Diabetes: 2003 American Diabetes Association Postgraduate Course. Diabetes Care
26: 2198-2203
[Full Text]
Iwaki, M., Matsuda, M., Maeda, N., Funahashi, T., Matsuzawa, Y., Makishima, M., Shimomura, I.
(2003). Induction of Adiponectin, a Fat-Derived Antidiabetic and Antiatherogenic Factor, by Nuclear Receptors. Diabetes
52: 1655-1663
[Abstract][Full Text]
Gavrila, A., Peng, C.-K., Chan, J. L., Mietus, J. E., Goldberger, A. L., Mantzoros, C. S.
(2003). Diurnal and Ultradian Dynamics of Serum Adiponectin in Healthy Men: Comparison with Leptin, Circulating Soluble Leptin Receptor, and Cortisol Patterns. J. Clin. Endocrinol. Metab.
88: 2838-2843
[Abstract][Full Text]
Lyon, C. J., Law, R. E., Hsueh, W. A.
(2003). Minireview: Adiposity, Inflammation, and Atherogenesis. Endocrinology
144: 2195-2200
[Abstract][Full Text]
Leow, M. K. S., Addy, C. L., Mantzoros, C. S.
(2003). Human Immunodeficiency Virus/Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome: Clinical Presentation, Pathophysiology, and Therapeutic Strategies. J. Clin. Endocrinol. Metab.
88: 1961-1976
[Full Text]
Sivitz, W. I., Wayson, S. M., Bayless, M. L., Larson, L. F., Sinkey, C., Bar, R. S., Haynes, W. G.
(2003). Leptin and Body Fat in Type 2 Diabetes and Monodrug Therapy. J. Clin. Endocrinol. Metab.
88: 1543-1553
[Abstract][Full Text]
Munoz, J., Gower, B. A.
(2003). Relationship between Serum Leptin Concentration and Low-Density Muscle in Postmenopausal Women. J. Clin. Endocrinol. Metab.
88: 1157-1161
[Abstract][Full Text]
Guldstrand, M., Ahren, B., Adamson, U.
(2003). Improved beta -cell function after standardized weight reduction in severely obese subjects. Am. J. Physiol. Endocrinol. Metab.
284: E557-E565
[Abstract][Full Text]
Halle, M., Persson, P. B.
(2003). Role of leptin and leptin receptor in inflammation. Am. J. Physiol. Regul. Integr. Comp. Physiol.
284: R760-R762
[Full Text]
Addy, C. L., Gavrila, A., Tsiodras, S., Brodovicz, K., Karchmer, A. W., Mantzoros, C. S.
(2003). Hypoadiponectinemia Is Associated with Insulin Resistance, Hypertriglyceridemia, and Fat Redistribution in Human Immunodeficiency Virus-Infected Patients Treated with Highly Active Antiretroviral Therapy. J. Clin. Endocrinol. Metab.
88: 627-636
[Abstract][Full Text]
Colombo, C., Haluzik, M., Cutson, J. J., Dietz, K. R., Marcus-Samuels, B., Vinson, C., Gavrilova, O., Reitman, M. L.
(2003). Opposite Effects of Background Genotype on Muscle and Liver Insulin Sensitivity of Lipoatrophic Mice. ROLE OF TRIGLYCERIDE CLEARANCE. J. Biol. Chem.
278: 3992-3999
[Abstract][Full Text]
Freemark, M.
(2003). Pharmacologic Approaches to the Prevention of Type 2 Diabetes in High Risk Pediatric Patients. J. Clin. Endocrinol. Metab.
88: 3-13
[Full Text]
Simha, V., Szczepaniak, L. S., Wagner, A. J., DePaoli, A. M., Garg, A.
(2003). Effect of Leptin Replacement on Intrahepatic and Intramyocellular Lipid Content in Patients With Generalized Lipodystrophy. Diabetes Care
26: 30-35
[Abstract][Full Text]
Laustsen, P. G., Michael, M. D., Crute, B. E., Cohen, S. E., Ueki, K., Kulkarni, R. N., Keller, S. R., Lienhard, G. E., Kahn, C. R.
(2002). Lipoatrophic diabetes in Irs1-/-/Irs3-/- double knockout mice. Genes Dev.
16: 3213-3222
[Abstract][Full Text]
Simha, V., Zerwekh, J. E., Sakhaee, K., Garg, A.
(2002). Effect of Subcutaneous Leptin Replacement Therapy on Bone Metabolism in Patients with Generalized Lipodystrophy. J. Clin. Endocrinol. Metab.
87: 4942-4945
[Abstract][Full Text]
Colombo, C., Cutson, J. J., Yamauchi, T., Vinson, C., Kadowaki, T., Gavrilova, O., Reitman, M. L.
(2002). Transplantation of Adipose Tissue Lacking Leptin Is Unable to Reverse the Metabolic Abnormalities Associated With Lipoatrophy. Diabetes
51: 2727-2733
[Abstract][Full Text]
Garg, A., Misra, A.
(2002). Hepatic Steatosis, Insulin Resistance, and Adipose Tissue Disorders. J. Clin. Endocrinol. Metab.
87: 3019-3022
[Full Text]
Grunfeld, C.
(2002). Leptin and the Immunosuppression of Malnutrition. J. Clin. Endocrinol. Metab.
87: 3038-3039
[Full Text]
Oral, E. A., Ruiz, E., Andewelt, A., Sebring, N., Wagner, A. J., Depaoli, A. M., Gorden, P.
(2002). Effect of Leptin Replacement on Pituitary Hormone Regulation in Patients with Severe Lipodystrophy. J. Clin. Endocrinol. Metab.
87: 3110-3117
[Abstract][Full Text]
Chou, C. J., Haluzik, M., Gregory, C., Dietz, K. R., Vinson, C., Gavrilova, O., Reitman, M. L.
(2002). WY14,643, a Peroxisome Proliferator-activated Receptor alpha (PPARalpha ) Agonist, Improves Hepatic and Muscle Steatosis and Reverses Insulin Resistance in Lipoatrophic A-ZIP/F-1 Mice. J. Biol. Chem.
277: 24484-24489
[Abstract][Full Text]
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