Leptin signaling as a therapeutic target of obesity

Bibliography

• Havel PJ. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004;53(Suppl 1):S143-51
   PubMed Web of Science ®Google Scholar
• Dardeno TA, Chou SH, Moon HS, et al. Leptin in human physiology and therapeutics. Front Neuroendocrinol 2010;31(3):377-93
   PubMedGoogle Scholar
• Frederich RC, Hamann A, Anderson S, et al. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1995;1(12):1311-14
   PubMed Web of Science ®Google Scholar
• Maffei M, Halaas J, Ravussin E, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995;1(11):1155-61
   PubMed Web of Science ®Google Scholar
• Considine RV. Regulation of leptin production. Rev Endocr Metab Disord 2001;2(4):357-63
   PubMedGoogle Scholar
• Sáinz N, Barrenetxe J, Moreno-Aliaga MJ, et al. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism 2015;64(1):35-46
   PubMed Web of Science ®Google Scholar
• Meister B. Control of food intake via leptin receptors in the hypothalamus. Vitam Horm 2000;59:265-304
   PubMedGoogle Scholar
• Martí A, Berraondo B, Martínez JA. Leptin: physiological actions. J Physiol Biochem 1999;55(1):43-9
   PubMedGoogle Scholar
• Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83(7):1263-71
   PubMed Web of Science ®Google Scholar
• Wada N, Hirako S, Takenoya F, et al. Leptin and its receptors. J Chem Neuroanat 2014;61-62:191-9
   PubMed Web of Science ®Google Scholar
• Barrenetxe J, Villaro AC, Guembe L, et al. Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes. Gut 2002;50(6):797-802
   PubMedGoogle Scholar
• Vaisse C, Halaas JL, Horvath CM, et al. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 1996;14(1):95-7
   PubMed Web of Science ®Google Scholar
• Myers MGJr. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res 2004;59:287-304
   PubMedGoogle Scholar
• Minokoshi Y, Alquier T, Furukawa N, et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 2004;428(6982):569-74
   PubMed Web of Science ®Google Scholar
• Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, et al. Role of obesity-associated dysfunctional adipose tissue in cancer: a molecular nutrition approach. Biochim Biophys Acta 2011;1807(6):664-78
   PubMed Web of Science ®Google Scholar
• Scarpace PJ, Matheny M. Leptin induction of UCP1 gene expression is dependent on sympathetic innervation. Am J Physiol 1998;275(2 Pt 1):E259-64
   PubMedGoogle Scholar
• Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269(5223):540-3
   PubMed Web of Science ®Google Scholar
• Hwa JJ, Fawzi AB, Graziano MP, et al. Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice. Am J Physiol 1997;272(4 Pt 2):R1204-9
   PubMedGoogle Scholar
• Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387(6636):903-8
   PubMed Web of Science ®Google Scholar
• Bates SH, Dundon TA, Seifert M, et al. LRb-STAT3 signaling is required for the neuroendocrine regulation of energy expenditure by leptin. Diabetes 2004;53(12):3067-73
   PubMedGoogle Scholar
• Niswender KD, Morton GJ, Stearns WH, et al. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 2001;413(6858):794-5
   PubMed Web of Science ®Google Scholar
• Dalamaga M, Chou SH, Shields K, et al. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab 2013;18(1):29-42
   PubMed Web of Science ®Google Scholar
• Fruhbeck G, Aguado M, Martinez JA. In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin. Biochem Biophys Res Commun 1997;240(3):590-4
   PubMed Web of Science ®Google Scholar
• Martínez JA, Aguado M, Frühbeck G. Interactions between leptin and NPY affecting lipid mobilization in adipose tissue. J Physiol Biochem 2000;56(1):1-8
   PubMedGoogle Scholar
• Buettner C, Muse ED, Cheng A, et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med 2008;14(6):667-75
   PubMed Web of Science ®Google Scholar
• Minokoshi Y, Kahn BB. Role of AMP-activated protein kinase in leptin-induced fatty acid oxidation in muscle. Biochem Soc Trans 2003;31(Pt 1):196-201
   PubMedGoogle Scholar
• Toyoshima Y, Gavrilova O, Yakar S, et al. Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2 diabetes. Endocrinology 2005;146(9):4024-35
   PubMedGoogle Scholar
• Ceddia RB, William WNJr, Curi R. Comparing effects of leptin and insulin on glucose metabolism in skeletal muscle: evidence for an effect of leptin on glucose uptake and decarboxylation. Int J Obes Relat Metab Disord 1999;23(1):75-82
   PubMedGoogle Scholar
• Tanaka T, Hidaka S, Masuzaki H, et al. Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification. Diabetes 2005;54(8):2365-74
   PubMedGoogle Scholar
• Roman EA, Reis D, Romanatto T, et al. Central leptin action improves skeletal muscle AKT, AMPK, and PGC1 alpha activation by hypothalamic PI3K-dependent mechanism. Mol Cell Endocrinol 2010;314(1):62-9
   PubMedGoogle Scholar
• Sáinz N, Rodríguez A, Catalán V, et al. Leptin reduces the expression and increases the phosphorylation of the negative regulators of GLUT4 traffic TBC1D1 and TBC1D4 in muscle of ob/ob mice. PLoS One 2012;7(1):e29389
   PubMed Web of Science ®Google Scholar
• Rahmouni K, Sigmund CD, Haynes WG, et al. Hypothalamic ERK mediates the anorectic and thermogenic sympathetic effects of leptin. Diabetes 2009;58(3):536-42
   PubMedGoogle Scholar
• Kirchgessner TG, Uysal KT, Wiesbrock SM, et al. Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest 1997;100(11):2777-82
   PubMedGoogle Scholar
• Finck BN, Kelley KW, Dantzer R, et al. In vivo and in vitro evidence for the involvement of tumor necrosis factor-alpha in the induction of leptin by lipopolysaccharide. Endocrinology 1998;139(5):2278-83
   PubMedGoogle Scholar
• Yamaguchi M, Murakami T, Tomimatsu T, et al. Autocrine inhibition of leptin production by tumor necrosis factor-alpha (TNF-alpha) through TNF-alpha type-I receptor in vitro. Biochem Biophys Res Commun 1998;244(1):30-4
   PubMedGoogle Scholar
• Houseknecht KL, Portocarrero CP, Ji S, et al. Growth hormone regulates leptin gene expression in bovine adipose tissue: correlation with adipose IGF-1 expression. J Endocrinol 2000;164(1):51-7
   PubMed Web of Science ®Google Scholar
• Escobar-Morreale HF, Escobar del Rey F, Morreale de Escobar G. Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology 1997;138(10):4485-8
   PubMed Web of Science ®Google Scholar
• Holdstock C, Engstrom BE, Ohrvall M, et al. Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab 2003;88(7):3177-83
   PubMed Web of Science ®Google Scholar
• Li RY, Song HD, Shi WJ, et al. Galanin inhibits leptin expression and secretion in rat adipose tissue and 3T3-L1 adipocytes. J Mol Endocrinol 2004;33(1):11-19
   PubMedGoogle Scholar
• Trayhurn P, Thomas ME, Duncan JS, et al. Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (oblob) mice. FEBS Lett 1995;368(3):488-90
   PubMed Web of Science ®Google Scholar
• Mizuno TM, Bergen H, Funabashi T, et al. Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity. Proc Natl Acad Sci USA 1996;93(8):3434-8
   PubMedGoogle Scholar
• Mueller WM, Gregoire FM, Stanhope KL, et al. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. Endocrinology 1998;139(2):551-8
   PubMed Web of Science ®Google Scholar
• Moreno-Aliaga MJ, Stanhope KL, Havel PJ. Transcriptional regulation of the leptin promoter by insulin-stimulated glucose metabolism in 3t3-l1 adipocytes. Biochem Biophys Res Commun 2001;283(3):544-8
   PubMed Web of Science ®Google Scholar
• Wellhoener P, Fruehwald-Schultes B, Kern W, et al. Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans. J Clin Endocrinol Metab 2000;85(3):1267-71
   PubMed Web of Science ®Google Scholar
• Moreno-Aliaga MJ, Swarbrick MM, Lorente-Cebrian S, et al. Sp1-mediated transcription is involved in the induction of leptin by insulin-stimulated glucose metabolism. J Mol Endocrinol 2007;38(5):537-46
   PubMedGoogle Scholar
• Su H, Jiang L, Carter-Su C, et al. Glucose enhances leptin signaling through modulation of AMPK activity. PLoS One 2012;7(2):e31636
   PubMed Web of Science ®Google Scholar
• Wang J, Liu R, Hawkins M, et al. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature 1998;393(6686):684-8
   PubMed Web of Science ®Google Scholar
• Banks WA, Coon AB, Robinson SM, et al. Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 2004;53(5):1253-60
   PubMed Web of Science ®Google Scholar
• Pérez-Matute P, Martí A, Martínez JA, et al. Effects of arachidonic acid on leptin secretion and expression in primary cultured rat adipocytes. J Physiol Biochem 2003;59(3):201-8
   PubMedGoogle Scholar
• Perez-Matute P, Marti A, Martinez JA, et al. Conjugated linoleic acid inhibits glucose metabolism, leptin and adiponectin secretion in primary cultured rat adipocytes. Mol Cell Endocrinol 2007;268(1-2):50-8
   PubMedGoogle Scholar
• Pérez-Matute P, Martínez JA, Martí A, et al. Linoleic acid decreases leptin and adiponectin secretion from primary rat adipocytes in the presence of insulin. Lipids 2007;42(10):913-20
   PubMedGoogle Scholar
• Moreno-Aliaga MJ, Lorente-Cebrian S, Martínez JA. Regulation of adipokine secretion by n-3 fatty acids. Proc Nutr Soc 2010;69(3):324-32
   PubMed Web of Science ®Google Scholar
• Hariri M, Ghiasvand R, Shiranian A, et al. Does omega-3 fatty acids supplementation affect circulating leptin levels? A systematic review and meta-analysis on randomized controlled clinical trials. Clin Endocrinol (Oxf) 2015;82(2):221-8
   PubMed Web of Science ®Google Scholar
• Rossi AS, Lombardo YB, Lacorte JM, et al. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats. Am J Physiol Regul Integr Comp Physiol 2005;289(2):R486-94
   PubMedGoogle Scholar
• Peyron-Caso E, Taverna M, Guerre-Millo M, et al. Dietary (n-3) polyunsaturated fatty acids up-regulate plasma leptin in insulin-resistant rats. J Nutr 2002;132(8):2235-40
   PubMedGoogle Scholar
• Prostek A, Gajewska M, Kamola D, et al. The influence of EPA and DHA on markers of inflammation in 3T3-L1 cells at different stages of cellular maturation. Lipids Health Dis 2014;13:3
   PubMedGoogle Scholar
• Pérez-Matute P, Martí A, Martínez JA, et al. Eicosapentaenoic fatty acid increases leptin secretion from primary cultured rat adipocytes: role of glucose metabolism. Am J Physiol Regul Integr Comp Physiol 2005;288(6):R1682-8
   PubMedGoogle Scholar
• Pérez-Matute P, Pérez-Echarri N, Martínez JA, et al. Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr 2007;97(2):389-98
   PubMed Web of Science ®Google Scholar
• Gray B, Steyn F, Davies PS, et al. Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management. Eur J Clin Nutr 2013;67(12):1234-42
   PubMed Web of Science ®Google Scholar
• Huerta AE, Navas-Carretero S, Prieto-Hontoria PL, et al. Effects of alpha-lipoic acid and eicosapentaenoic acid in overweight and obese women during weight loss. Obesity (Silver Spring) 2015;23(2):313-21
   PubMed Web of Science ®Google Scholar
• Kong J, Chen Y, Zhu G, et al. 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue. J Endocrinol 2013;216(2):265-71
   PubMed Web of Science ®Google Scholar
• Menéndez C, Lage M, Peino R, et al. Retinoic acid and vitamin D(3) powerfully inhibit in vitro leptin secretion by human adipose tissue. J Endocrinol 2001;170(2):425-31
   PubMed Web of Science ®Google Scholar
• Spina A, Sorvillo L, Esposito A, et al. Inorganic phosphate as a signaling molecule: a potential strategy in osteosarcoma treatment. Curr Pharm Des 2013;19(30):5394-403
   PubMedGoogle Scholar
• Anderson JJ. Potential health concerns of dietary phosphorus: cancer, obesity, and hypertension. Ann N Y Acad Sci 2013;1301:1-8
   PubMedGoogle Scholar
• Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, et al. Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes. Mol Nutr Food Res 2011;55(7):1059-69
   PubMedGoogle Scholar
• Fernández-Galilea M, Pérez-Matute P, Prieto-Hontoria PL, et al. alpha-lipoic acid reduces fatty acid esterification and lipogenesis in adipocytes from overweight/obese subjects. Obesity (Silver Spring) 2014;22(10):2210-15
   PubMed Web of Science ®Google Scholar
• Walsh AM, Sweeney T, Bahar B, et al. Multi-functional roles of chitosan as a potential protective agent against obesity. PLoS One 2013;8(1):e53828
   PubMedGoogle Scholar
• Ioffe E, Moon B, Connolly E, et al. Abnormal regulation of the leptin gene in the pathogenesis of obesity. Proc Natl Acad Sci USA 1998;95(20):11852-7
   PubMedGoogle Scholar
• Myers MGJr, Heymsfield SB, Haft C, et al. Challenges and opportunities of defining clinical leptin resistance. Cell Metab 2012;15(2):150-6
   PubMed Web of Science ®Google Scholar
• Caro JF, Kolaczynski JW, Nyce MR, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996;348(9021):159-61
   PubMed Web of Science ®Google Scholar
• Martin RL, Perez E, He YJ, et al. Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation. Metabolism 2000;49(11):1479-84
   PubMedGoogle Scholar
• Leon-Cabrera S, Solis-Lozano L, Suarez-Alvarez K, et al. Hyperleptinemia is associated with parameters of low-grade systemic inflammation and metabolic dysfunction in obese human beings. Front Integr Neurosci 2013;7:62
   PubMedGoogle Scholar
• Hsuchou H, Kastin AJ, Mishra PK, et al. C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation. Cell Physiol Biochem 2012;30(5):1109-19
   PubMed Web of Science ®Google Scholar
• Borges Bde C, Rorato R, Uchoa ET, et al. High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus. Am J Physiol Regul Integr Comp Physiol 2014;306(1):R34-44
   PubMedGoogle Scholar
• Gamber KM, Huo L, Ha S, et al. Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. PLoS One 2012;7(1):e30485
   PubMed Web of Science ®Google Scholar
• Olofsson LE, Unger EK, Cheung CC, et al. Modulation of AgRP-neuronal function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resistance. Proc Natl Acad Sci USA 2013;110(8):E697-706
   PubMedGoogle Scholar
• Liu ZJ, Bian J, Zhao YL, et al. Lentiviral vector-mediated knockdown of SOCS3 in the hypothalamus protects against the development of diet-induced obesity in rats. Diabetes Obes Metab 2011;13(10):885-92
   PubMedGoogle Scholar
• Scarpace PJ, Matheny M, Tumer N, et al. Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats. Diabetologia 2005;48(6):1075-83
   PubMedGoogle Scholar
• Han Y, Joe Y, Seo E, et al. The hyperleptinemia and ObRb expression in hyperphagic obese rats. Biochem Biophys Res Commun 2010;394(1):70-4
   PubMedGoogle Scholar
• Koch CE, Lowe C, Pretz D, et al. High-fat diet induces leptin resistance in leptin-deficient mice. J Neuroendocrinol 2013;26(2):58-67
   Google Scholar
• Knight ZA, Hannan KS, Greenberg ML, et al. Hyperleptinemia is required for the development of leptin resistance. PLoS ONE 2010;5(6):e11376
   PubMedGoogle Scholar
• Choi SJ, Kim F, Schwartz MW, et al. Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids. Am J Physiol Endocrinol Metab 2010;298(6):E1122-30
   PubMed Web of Science ®Google Scholar
• Haring SJ, Harris RB. The relation between dietary fructose, dietary fat and leptin responsiveness in rats. Physiol Behav 2011;104(5):914-22
   PubMedGoogle Scholar
• Shapiro A, Mu W, Roncal C, et al. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am J Physiol Regul Integr Comp Physiol 2008;295(5):R1370-5
   PubMed Web of Science ®Google Scholar
• Shapiro A, Tumer N, Gao Y, et al. Prevention and reversal of diet-induced leptin resistance with a sugar-free diet despite high fat content. Br J Nutr 2011;106(3):390-7
   PubMedGoogle Scholar
• Ravussin Y, Koren O, Spor A, et al. Responses of gut microbiota to diet composition and weight loss in lean and obese mice. Obesity (Silver Spring) 2012;20(4):738-47
   PubMed Web of Science ®Google Scholar
• Schele E, Grahnemo L, Anesten F, et al. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system. Endocrinology 2013;154(10):3643-51
   PubMed Web of Science ®Google Scholar
• Rajala MW, Patterson CM, Opp JS, et al. Leptin acts independently of food intake to modulate gut microbial composition in male mice. Endocrinology 2014;155(3):748-57
   PubMedGoogle Scholar
• Strobel A, Issad T, Camoin L, et al. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998;18(3):213-15
   PubMedGoogle Scholar
• Mazen I, El-Gammal M, Abdel-Hamid M, et al. A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient. Mol Genet Metab 2009;97(4):305-8
   PubMedGoogle Scholar
• Fischer-Posovszky P, von Schnurbein J, Moepps B, et al. A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness. J Clin Endocrinol Metab 2010;95(6):2836-40
   PubMedGoogle Scholar
• Farooqi IS, O’Rahilly S. 20 years of leptin: human disorders of leptin action. J Endocrinol 2014;223(1):T63-70
   PubMed Web of Science ®Google Scholar
• Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341(12):879-84
   PubMed Web of Science ®Google Scholar
• Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002;110(8):1093-103
   PubMed Web of Science ®Google Scholar
• Gibson WT, Farooqi IS, Moreau M, et al. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab 2004;89(10):4821-6
   PubMed Web of Science ®Google Scholar
• Farooqi IS, Bullmore E, Keogh J, et al. Leptin regulates striatal regions and human eating behavior. Science 2007;317(5843):1355
   PubMed Web of Science ®Google Scholar
• Licinio J, Caglayan S, Ozata M, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci USA 2004;101(13):4531-6
   PubMed Web of Science ®Google Scholar
• Williamson DA, Ravussin E, Wong ML, et al. Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy. Appetite 2005;45(1):75-80
   PubMedGoogle Scholar
• Heymsfield SB, Fong TM, Gantz I, et al. Fat and energy partitioning: longitudinal observations in leptin-treated adults homozygous for a Lep mutation. Obesity (Silver Spring) 2006;14(2):258-65
   PubMedGoogle Scholar
• Baicy K, London ED, Monterosso J, et al. Leptin replacement alters brain response to food cues in genetically leptin-deficient adults. Proc Natl Acad Sci USA 2007;104(46):18276-9
   PubMed Web of Science ®Google Scholar
• Berman SM, Paz-Filho G, Wong ML, et al. Effects of leptin deficiency and replacement on cerebellar response to food-related cues. Cerebellum 2013;12(1):59-67
   PubMedGoogle Scholar
• Frank S, Heni M, Moss A, et al. Long-term stabilization effects of leptin on brain functions in a leptin-deficient patient. PLoS One 2013;8(6):e65893
   PubMedGoogle Scholar
• Frank S, Heni M, Moss A, et al. Leptin therapy in a congenital leptin-deficient patient leads to acute and long-term changes in homeostatic, reward, and food-related brain areas. J Clin Endocrinol Metab 2011;96(8):E1283-7
   PubMedGoogle Scholar
• Galgani JE, Greenway FL, Caglayan S, et al. Leptin replacement prevents weight loss-induced metabolic adaptation in congenital leptin-deficient patients. J Clin Endocrinol Metab 2010;95(2):851-5
   PubMedGoogle Scholar
• von Schnurbein J, Heni M, Moss A, et al. Rapid improvement of hepatic steatosis after initiation of leptin substitution in a leptin-deficient girl. Horm Res Paediatr 2013;79(5):310-17
   PubMedGoogle Scholar
• von Schnurbein J, Moss A, Nagel SA, et al. Leptin substitution results in the induction of menstrual cycles in an adolescent with leptin deficiency and hypogonadotropic hypogonadism. Horm Res Paediatr 2012;77(2):127-33
   PubMedGoogle Scholar
• Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999;282(16):1568-75
   PubMed Web of Science ®Google Scholar
• Hukshorn CJ, Saris WH, Westerterp-Plantenga MS, et al. Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J Clin Endocrinol Metab 2000;85(11):4003-9
   PubMed Web of Science ®Google Scholar
• Westerterp-Plantenga MS, Saris WH, Hukshorn CJ, et al. Effects of weekly administration of pegylated recombinant human OB protein on appetite profile and energy metabolism in obese men. Am J Clin Nutr 2001;74(4):426-34
   PubMedGoogle Scholar
• Hukshorn CJ, van Dielen FM, Buurman WA, et al. The effect of pegylated recombinant human leptin (PEG-OB) on weight loss and inflammatory status in obese subjects. Int J Obes Relat Metab Disord 2002;26(4):504-9
   PubMed Web of Science ®Google Scholar
• Hukshorn CJ, Menheere PP, Westerterp-Plantenga MS, et al. The effect of pegylated human recombinant leptin (PEG-OB) on neuroendocrine adaptations to semi-starvation in overweight men. Eur J Endocrinol 2003;148(6):649-55
   PubMedGoogle Scholar
• Lejeune MP, Hukshorn CJ, Saris WH, et al. Effects of very low calorie diet induced body weight loss with or without human pegylated recombinant leptin treatment on changes in ghrelin and adiponectin concentrations. Physiol Behav 2007;91(2-3):274-80
   PubMedGoogle Scholar
• Mittendorfer B, Horowitz JF, DePaoli AM, et al. Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes. Diabetes 2011;60(5):1474-7
   PubMed Web of Science ®Google Scholar
• Shetty GK, Matarese G, Magkos F, et al. Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet. Eur J Endocrinol 2011;165(2):249-54
   PubMed Web of Science ®Google Scholar
• Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011;365(17):1597-604
   PubMed Web of Science ®Google Scholar
• Kissileff HR, Thornton JC, Torres MI, et al. Leptin reverses declines in satiation in weight-reduced obese humans. Am J Clin Nutr 2012;95(2):309-17
   PubMed Web of Science ®Google Scholar
• Rosenbaum M, Goldsmith R, Bloomfield D, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005;115(12):3579-86
   PubMed Web of Science ®Google Scholar
• Rosenbaum M, Murphy EM, Heymsfield SB, et al. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002;87(5):2391-4
   PubMed Web of Science ®Google Scholar
• Fogteloo J, Meinders E, Frolich M, et al. The decline in plasma leptin in response to calorie restriction predicts the effects of adjunctive leptin treatment on body weight in humans. Eur J Intern Med 2003;14(7):415-18
   PubMedGoogle Scholar
• Rosenbaum M, Sy M, Pavlovich K, et al. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J Clin Invest 2008;118(7):2583-91
   PubMed Web of Science ®Google Scholar
• Conroy R, Girotra M, Shane E, et al. Leptin administration does not prevent the bone mineral metabolism changes induced by weight loss. Metabolism 2011;60(9):1222-6
   PubMedGoogle Scholar
• Korner J, Conroy R, Febres G, et al. Randomized double-blind placebo-controlled study of leptin administration after gastric bypass. Obesity (Silver Spring) 2013;21(5):951-6
   PubMed Web of Science ®Google Scholar
• Fogteloo AJ, Pijl H, Frolich M, et al. Effects of recombinant human leptin treatment as an adjunct of moderate energy restriction on body weight, resting energy expenditure and energy intake in obese humans. Diabetes Nutr Metab 2003;16(2):109-14
   PubMedGoogle Scholar
• Friedman J. 20 years of leptin: leptin at 20: an overview. J Endocrinol 2014;223(1):T1-8
   PubMed Web of Science ®Google Scholar
• Farooqi IS, Keogh JM, Kamath S, et al. Partial leptin deficiency and human adiposity. Nature 2001;414(6859):34-5
   PubMed Web of Science ®Google Scholar
• Roth JD, Roland BL, Cole RL, et al. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 2008;105(20):7257-62
   PubMed Web of Science ®Google Scholar
• Ravussin E, Smith SR, Mitchell JA, et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring) 2009;17(9):1736-43
   PubMed Web of Science ®Google Scholar
• Paz-Filho G, Mastronardi CA, Licinio J. Leptin treatment: facts and expectations. Metabolism 2014;64(1):146-56
   PubMedGoogle Scholar
• Muller TD, Sullivan LM, Habegger K, et al. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. J Pept Sci 2012;18(6):383-93
   PubMed Web of Science ®Google Scholar
• Wu Y, Yu Y, Szabo A, et al. Central inflammation and leptin resistance are attenuated by ginsenoside Rb1 treatment in obese mice fed a high-fat diet. PLoS ONE 2014;9(3):e92618
   PubMedGoogle Scholar
• Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010;142(5):687-98
   PubMed Web of Science ®Google Scholar
• Itariu BK, Zeyda M, Hochbrugger EE, et al. Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial. Am J Clin Nutr 2012;96(5):1137-49
   PubMed Web of Science ®Google Scholar
• Lorente-Cebrian S, Bustos M, Marti A, et al. Eicosapentaenoic acid inhibits tumour necrosis factor-alpha-induced lipolysis in murine cultured adipocytes. J Nutr Biochem 2012;23(3):218-27
   PubMedGoogle Scholar
• Wellhauser L, Belsham DD. Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J Neuroinflammation 2014;11:60
   PubMed Web of Science ®Google Scholar
• Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature 2014;510(7503):92-101
   PubMed Web of Science ®Google Scholar
• Titos E, Rius B, Gonzalez-Periz A, et al. Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J Immunol 2011;187(10):5408-18
   PubMed Web of Science ®Google Scholar
• Gonzalez-Periz A, Horrillo R, Ferre N, et al. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. Faseb J 2009;23(6):1946-57
   PubMed Web of Science ®Google Scholar
• Hellmann J, Tang Y, Kosuri M, et al. Resolvin D1 decreases adipose tissue macrophage accumulation and improves insulin sensitivity in obese-diabetic mice. Faseb J 2011;25(7):2399-407
   PubMed Web of Science ®Google Scholar
• Neuhofer A, Zeyda M, Mascher D, et al. Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation. Diabetes 2013;62(6):1945-56
   PubMed Web of Science ®Google Scholar
• White PJ, St-Pierre P, Charbonneau A, et al. Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis. Nat Med 2014;20(6):664-9
   PubMedGoogle Scholar
• Bazan NG. The docosanoid neuroprotectin D1 induces homeostatic regulation of neuroinflammation and cell survival. Prostaglandins Leukot Essent Fatty Acids 2013;88(1):127-9
   PubMed Web of Science ®Google Scholar
• Banks WA. Is obesity a disease of the blood-brain barrier? Physiological, pathological, and evolutionary considerations. Curr Pharm Des 2003;9(10):801-9
   PubMed Web of Science ®Google Scholar
• Yi X, Yuan D, Farr SA, et al. Pluronic modified leptin with increased systemic circulation, brain uptake and efficacy for treatment of obesity. J Control Release 2014;191:34-46
   PubMed Web of Science ®Google Scholar