The Young Neuroendocrinologists Prize Reviews offer the winner of the top prize available from international neuroendocrinology societies for young scientists the opportunity to write a short review on the subject of their work. Dr Alexander Tups from the University of Marburg was awarded the Mick Harbuz Award for young scientists by the British Society for Neuroendocrinology in 2009 for his work on the implications of hypothalamic PI3 kinase in nutrient sensing, glucose metabolism and energy homeostasis.
Physiological Models of Leptin Resistance
Version of Record online: 1 SEP 2009
© 2009 The Author. Journal Compilation © 2009 Blackwell Publishing Ltd
Journal of Neuroendocrinology
Volume 21, Issue 11, pages 961–971, November 2009
How to Cite
Tups, A. (2009), Physiological Models of Leptin Resistance. Journal of Neuroendocrinology, 21: 961–971. doi: 10.1111/j.1365-2826.2009.01916.x
- Issue online: 21 OCT 2009
- Version of Record online: 1 SEP 2009
- Received: 25 February 2009, revised 23 July 2009, accepted 10 August 2009
- 1The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 1953; 140: 578–596..
- 2Molecular and anatomical determinants of central leptin resistance. Nat Neurosci 2005; 8: 566–570., .
- 3Central nervous system control of food intake. Nature 2000; 404: 661–671., , , , .
- 4Leptin transport across the blood-brain barrier: implications for the cause and treatment of obesity. Curr Pharm Des 2001; 7: 125–133..
- 5Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am J Physiol Endocrinol Metab 2003; 285: E10–15., .
- 6The geometry of leptin action in the brain: more complicated than a simple ARC. Cell Metab 2009; 9: 117–123., , , .
- 7Differential leptin access into the brain – a hierarchical organization of hypothalamic leptin target sites? Physiol Behav 2008; 94: 664–669..
- 8Effects of leptin on rat ventromedial hypothalamic neurons. Endocrinology 2008; 149: 5146–5154., , , .
- 9Photoperiod regulates growth, puberty and hypothalamic neuropeptide and receptor gene expression in female Siberian hamsters. Endocrinology 2000; 141: 4349–4356., , , , , , .
- 10Regulation of leptin receptor, POMC and AGRP gene expression by photoperiod and food deprivation in the hypothalamic arcuate nucleus of the male Siberian hamster (Phodopus sungorus). Appetite 2000; 34: 109–111., , , .
- 11Photoperiod regulates arcuate nucleus POMC, AGRP, and leptin receptor mRNA in Siberian hamster hypothalamus. Am J Physiol Regul Integr Comp Physiol 2000; 278: R271–R281., , , , .
- 12Seasonally inappropriate body weight induced by food restriction: effect on hypothalamic gene expression in male Siberian hamsters. Endocrinology 2001; 142: 4173–4181., , , , , .
- 13Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett 1996; 387: 113–116., , , , , .
- 14Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 1997; 390: 521–525., , , , .
- 15Intracellular signalling Key enzyme in leptin-induced anorexia. Nature 2001; 413: 794–795., , , , , .
- 16Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 1996; 14: 95–97., , , , , .
- 17Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res 2004; 59: 287–304..
- 18The leptin receptor. J Biol Chem 1997; 272: 6093–6096..
- 19Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc Natl Acad Sci USA 1999; 96: 9677–9682., .
- 20Leptin receptor (OB-R) signaling cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. J Biol Chem 1997; 272: 4065–4071., , , , .
- 21Activation of downstream signals by the long form of the leptin receptor. J Biol Chem 2000; 275: 14563–14572., , , .
- 22Divergent roles of SHP-2 in ERK activation by leptin receptors. J Biol Chem 2001; 276: 4747–4755., , , , , , , , .
- 23The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms. J Biol Chem 2007; 282: 31019–31027., , , , , .
- 24Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nat Med 2004; 10: 734–738., , , , , .
- 25Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 2004; 10: 739–743., , , , , , , , , .
- 26Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 1999; 283: 1544–1548., , , , , , , , , , , , , .
- 27Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol 2000; 20: 5479–5489., , , , , , , , , , , , , .
- 28Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis. Diabetes 2002; 51: 2405–2411., , , , , , , , , , , , , .
- 29PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci USA 2002; 99: 11357–11362., , , , , , , , , , , , , , , , , , , , , .
- 30SOCS-3 expression in leptin-sensitive neurons of the hypothalamus of fed and fasted rats. Regul Pept 2000; 92: 9–15., , .
- 31Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 2004; 145: 4880–4889., , .
- 32Leptin and insulin action in the central nervous system. Nutr Rev 2002; 60: S20–S29., , .
- 33Diabetes, obesity, and the brain. Science 2005; 307: 375–379., .
- 34Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol [B] 1992; 162: 696–706., .
- 35Altered expression of SOCS3 in the hypothalamic arcuate nucleus during seasonal body mass changes in the field vole, Microtus agrestis. J Neuroendocrinol 2007; 19: 83–94., , , , , , , , , , .
- 36Region-specific reduction in leptin-induced phosphorylation of signal transducer and activator of transcription-3 (STAT3) in the rat hypothalamus is associated with leptin resistance during pregnancy. Endocrinology 2004; 145: 3704–3711., .
- 37Suppression of leptin receptor messenger ribonucleic acid and leptin responsiveness in the ventromedial nucleus of the hypothalamus during pregnancy in the rat. Endocrinology 2005; 146: 3868–3874., .
- 38Photoperiodic regulation of leptin resistance in the seasonally breeding Siberian hamster (Phodopus sungorus). Endocrinology 2002; 143: 3083–3095., , , , , , , , .
- 39Photoperiodic regulation of leptin sensitivity in the Siberian hamster, Phodopus sungorus, is reflected in arcuate nucleus SOCS-3 (suppressor of cytokine signaling) gene expression. Endocrinology 2004; 145: 1185–1193., , , , , , .
- 40The suppressor of cytokine signalling 3, SOCS3, may be one critical modulator of seasonal body weight changes in the Siberian hamster, Phodopus sungorus. J Neuroendocrinol 2006; 18: 139–145., , , , , .
- 41Short photoperiod reduces leptin gene expression in white and brown adipose tissue of Djungarian hamsters. FEBS Lett 1996; 399: 290–294., , , .
- 42Modulation of leptin sensitivity by short photoperiod acclimation in the Djungarian hamster, Phodopus sungorus. J Comp Physiol [B] 2000; 170: 37–43., , .
- 43Photoperiod regulates leptin sensitivity in field voles, Microtus agrestis. J Comp Physiol [B] 2006; 176: 153–163., , , , , .
- 44Role of photoperiod and melatonin in seasonal acclimatization of the Djungarian hamster, Phodopus sungorus. Int J Biometeorol 1982; 26: 329–337., .
- 45Photoperiod and ambient temperature as environmental cues for seasonal thermogenic adaptation in the Djungarian hamster, Phodopus sungorus. Int J Biometeorol 1982; 26: 339–345., , , .
- 46Photoperiodic programming of body weight through the neuroendocrine hypothalamus. J Endocrinol 2003; 177: 27–34., , , .
- 47Leptin acts on metabolism in a photoperiod-dependent manner, but has no effect on reproductive function in the seasonally breeding Siberian hamster (Phodopus sungorus). Endocrinology 2000; 141: 4128–4135., , , , , , , .
- 48Rheostasis: the physiology of change. New York: Oxford University Press, 1990..
- 49Are the short-photoperiod-induced decreases in serum prolactin responsible for the seasonal changes in energy balance in Syrian and Siberian hamsters? J Exp Zool 1987; 244: 437–454., , .
- 50Influence of short days on diurnal patterns of serum gonadotrophins and prolactin concentrations in the male Djungarian hamster, Phodopus sungorus. J Reprod Fertil 1987; 80: 167–174., .
- 51Hormonal regulation of the annual pelage color cycle in the Djungarian hamster, Phodopus sungorus II role of prolactin. J Exp Zool 1984; 230: 97–103., .
- 52Pineal and pituitary involvement in the photoperiodic regulation of body weight, coat color and testicular size of the Djungarian hamster, Phodopus sungorus. Biol Reprod 1988; 39: 489–498., .
- 53Central sites mediating reproductive responses to melatonin in juvenile male Siberian hamsters. Brain Res 1992; 598: 98–106., .
- 54Suppression of prolactin-induced signal transducer and activator of transcription 5b signaling and induction of suppressors of cytokine signaling messenger ribonucleic acid in the hypothalamic arcuate nucleus of the rat during late pregnancy and lactation. Endocrinology 2006; 147: 4996–5005., , , , , .
- 55Expression of mRNA for prolactin receptor (long form) in dopamine and pro-opiomelanocortin neurones in the arcuate nucleus of non-pregnant and lactating rats. J Neuroendocrinol 2005; 17: 827–835., .
- 56Insulin induces suppressor of cytokine signaling-3 tyrosine phosphorylation through janus-activated kinase. J Biol Chem 2001; 276: 24614–24620., , , , .
- 57Differential expression of the two forms of prolactin receptor mRNA within microdissected hypothalamic nuclei of the rat. Brain Res Mol Brain Res 1998; 59: 1–12., .
- 58Distribution of prolactin receptor immunoreactivity in the brain of estrogen-treated, ovariectomized rats. J Comp Neurol 1998; 394: 462–474., .
- 59Hormonal regulation of suppressors of cytokine signaling (SOCS) messenger ribonucleic acid in the arcuate nucleus during late pregnancy. Endocrinology 2008; 149: 3206–3214., , .
- 60Lack of cross-desensitization between leptin and prolactin signaling pathways despite the induction of suppressor of cytokine signaling 3 and PTP-1B. J Endocrinol 2007; 195: 341–350., , , , , , , .
- 61Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 1994; 13: 1177–1185., , .
- 62Photoperiodic regulation of insulin receptor mRNA and intracellular insulin signaling in the arcuate nucleus of the Siberian hamster, Phodopus sungorus. Am J Physiol Regul Integr Comp Physiol 2006; B: R643–650., , , , , .
- 63Neurons with access to the general circulation in the central nervous system of the rat: a retrograde tracing study with fluoro-gold. Neuroscience 1991; 44: 655–662..
- 64Morphology and function of capillary networks in subregions of the rat tuber cinereum. Cell Tissue Res 1992; 267: 437–448., , , , .
- 65Induction of central leptin resistance in hyperphagic pseudopregnant rats by chronic prolactin infusion. Endocrinology 2008; 149: 1049–1055., .
- 66From feeding one to feeding many: hormone-induced changes in bodyweight homeostasis during pregnancy. J Physiol 2008; 586: 387–397., , .
- 67Leptin in pregnancy: an update. Biol Reprod 2006; 74: 218–229., .
- 68Prolactin/leptin interactions in the control of food intake in rats. Endocrinology 2007; 148: 5977–5983., .
- 69Prolactin, growth hormone, erythropoietin and granulocyte-macrophage colony stimulating factor induce MGF-Stat5 DNA binding activity. EMBO J 1995; 14: 005–013., , , , , , , .
- 70SOCS3 as a tumor suppressor in breast cancer cells, and its regulation by PRL. Int J Cancer 2009; 124: 1756–1766., , , .
- 71Loss of hypothalamic response to leptin during pregnancy associated with development of melanocortin resistance. J Neuroendocrinol 2009; 21: 449–456., , , , , .
- 72Initiation and perpetuation of obesity and obesity resistance in rats. Am J Physiol 1989; 256: R766–R771., , .
- 73Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 2009; 296: R521–R527., , , .
- 74Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab 2008; 7: 179–185., , , , , .
- 75Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset. Am J Physiol Regul Integr Comp Physiol 2004; 286: R143–R150., , .
- 76Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab 2009; 296: E1003–E1012., , , , , , , , , , , .
- 77Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008; 135: 61–73., , , , , .
- 78High-fat diet induces apoptosis of hypothalamic neurons. PLoS ONE 2009; 4: e5045., , , , , , , , , , .