Skip to main content
SpringerLink
Log in

Leptin and Intermediary Metabolism: Focus on Glucoregulation and Lipids

  • Chapter
  • First Online:
Leptin

  • 1410 Accesses

Abstract

In the first studies of leptin administration to obese mice it was noted that low dose leptin, which did not alter food intake or body weight, decreased blood glucose. This observation initiated investigation into the mechanisms through which leptin regulated intermediary metabolism independent of effects on caloric intake and body weight. With leptin receptors present in the central nervous system and on peripheral tissues, metabolic effects of leptin can be mediated via activation of neural pathways in the brain or by direct binding to the major metabolic tissues including the liver, skeletal muscle, adipose tissue, and pancreas. Leptin regulation of glucose and lipid homeostasis has been observed in multiple rodent models and in humans with hypoleptinemic lipodystrophy. Understanding the mechanisms through which leptin regulates intermediary metabolism is anticipated to result in better therapeutic interventions to correct dysregulated metabolism in obesity and diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–32.

    Article  CAS  PubMed  Google Scholar 

  2. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269:540–3.

    Article  CAS  PubMed  Google Scholar 

  3. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269:543–6.

    Article  CAS  PubMed  Google Scholar 

  4. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995;269:546–9.

    Article  CAS  PubMed  Google Scholar 

  5. Ceddia RB, William Jr WN, Curi R. Leptin increases glucose transport and utilization in skeletal muscle in vitro. Gen Pharmacol. 1998;31(5):799–801.

    Article  CAS  PubMed  Google Scholar 

  6. Harris RB. Acute and chronic effects of leptin on glucose utilization in lean mice. Biochem Biophys Res Commun. 1998;245(2):502–9.

    Article  CAS  PubMed  Google Scholar 

  7. Berti L, Gammeltoft S. Leptin stimulates glucose uptake in C2C12 muscle cells by activation of ERK2. Mol Cell Endocrinol. 1999;157(1–2):121–30.

    Article  CAS  PubMed  Google Scholar 

  8. Zierath JR, Frevert EU, Ryder JW, Berggren PO, Kahn BB. Evidence against a direct effect of leptin on glucose transport in skeletal muscle and adipocytes. Diabetes. 1998;47(1):1–4.

    Article  CAS  PubMed  Google Scholar 

  9. Sweeney G, Keen J, Somwar R, Konrad D, Garg R, Klip A. High leptin levels acutely inhibit insulin-stimulated glucose uptake without affecting glucose transporter 4 translocation in l6 rat skeletal muscle cells. Endocrinology. 2001;142(11):4806–12.

    Article  CAS  PubMed  Google Scholar 

  10. Hennige AM, Stefan N, Kapp K, Lehmann R, Weigert C, Beck A, Moeschel K, Mushack J, Schleicher E, Häring HU. Leptin down-regulates insulin action through phosphorylation of serine-318 in insulin receptor substrate 1. FASEB J. 2006;20(8):1206–8.

    Article  CAS  PubMed  Google Scholar 

  11. Müller G, Ertl J, Gerl M, Preibisch G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem. 1997;272(16):10585–93.

    Article  PubMed  Google Scholar 

  12. Mick G, Vanderbloomer T, Fu CL, McCormick K. Leptin does not affect adipocyte glucose metabolism: studies in fresh and cultured adipocytes. Metabolism. 1998;47(11):1360–5.

    Article  CAS  PubMed  Google Scholar 

  13. Ranganathan S, Ciaraldi TP, Henry RR, Mudaliar S, Kern PA. Lack of effect of leptin on glucose transport, lipoprotein lipase, and insulin action in adipose and muscle cells. Endocrinology. 1998;139(5):2509–13.

    CAS  PubMed  Google Scholar 

  14. Aprath-Husmann I, Röhrig K, Gottschling-Zeller H, Skurk T, Scriba D, Birgel M, Hauner H. Effects of leptin on the differentiation and metabolism of human adipocytes. Int J Obes Relat Metab Disord. 2001;25(10):1465–70.

    Article  CAS  PubMed  Google Scholar 

  15. Yau SW, Henry BA, Russo VC, McConell GK, Clarke IJ, Werther GA, Sabin MA. Leptin enhances insulin sensitivity by direct and sympathetic nervous system regulation of muscle IGFBP-2 expression—evidence from non-rodent models. Endocrinology. 2014;155(6):2133–43.

    Article  CAS  PubMed  Google Scholar 

  16. Aiston S, Agius L. Leptin enhances glycogen storage in hepatocytes by inhibition of phosphorylase and exerts an additive effect with insulin. Diabetes. 1999;48(1):15–20.

    Article  CAS  PubMed  Google Scholar 

  17. Ceddia RB, Lopes G, Souza HM, Borba-Murad GR, William Jr WN, Bazotte RB, Curi R. Acute effects of leptin on glucose metabolism of in situ rat perfused livers and isolated hepatocytes. Int J Obes Relat Metab Disord. 1999;23(11):1207–12.

    Article  CAS  PubMed  Google Scholar 

  18. Nemecz M, Preininger K, Englisch R, Fürnsinn C, Schneider B, Waldhäusl W, Roden M. Acute effect of leptin on hepatic glycogenolysis and gluconeogenesis in perfused rat liver. Hepatology. 1999;29(1):166–72.

    Article  CAS  PubMed  Google Scholar 

  19. Shimabukuro M, Koyama K, Chen G, Wang MY, Trieu F, Lee Y, Newgard CB, Unger RH. Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proc Natl Acad Sci U S A. 1997;94(9):4637–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Muoio DM, Dohm GL, Tapscott EB, Coleman RA. Leptin opposes insulin’s effects on fatty acid partitioning in muscles isolated from obese ob/ob mice. Am J Physiol. 1999;276(5 Pt 1):E913–21.

    CAS  PubMed  Google Scholar 

  21. Steinberg GR, Dyck DJ. Development of leptin resistance in rat soleus muscle in response to high-fat diets. Am J Physiol Endocrinol Metab. 2000;279(6):E1374–82.

    CAS  PubMed  Google Scholar 

  22. Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ. Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. Am J Physiol Endocrinol Metab. 2002;283(1):E187–92.

    CAS  PubMed  Google Scholar 

  23. Siegrist-Kaiser CA, Pauli V, Juge-Aubry CE, Boss O, Pernin A, Chin WW, Cusin I, Rohner-Jeanrenaud F, Burger AG, Zapf J, Meier CA. Direct effects of leptin on brown and white adipose tissue. J Clin Invest. 1997;100(11):2858–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Wang MY, Lee Y, Unger RH. Novel form of lipolysis induced by leptin. J Biol Chem. 1999;274(25):17541–4.

    Article  CAS  PubMed  Google Scholar 

  25. Frühbeck G, Aguado M, Gómez-Ambrosi J, Martínez JA. Lipolytic effect of in vivo leptin administration on adipocytes of lean and ob/ob mice, but not db/db mice. Biochem Biophys Res Commun. 1998;250(1):99–102.

    Article  PubMed  Google Scholar 

  26. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Müller C, Carling D, Kahn BB. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415(6869):339–43.

    Article  CAS  PubMed  Google Scholar 

  27. Lee Y, Wang MY, Kakuma T, Wang ZW, Babcock E, McCorkle K, Higa M, Zhou YT, Unger RH. Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia. J Biol Chem. 2001;276(8):5629–35.

    Article  CAS  PubMed  Google Scholar 

  28. Huang W, Dedousis N, Bhatt BA, O’Doherty RM. Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in diet-induced obesity. J Biol Chem. 2004;279(21):21695–700.

    Article  CAS  PubMed  Google Scholar 

  29. Huang W, Dedousis N, Bandi A, Lopaschuk GD, O’Doherty RM. Liver triglyceride secretion and lipid oxidative metabolism are rapidly altered by leptin in vivo. Endocrinology. 2006;147(3):1480–7.

    Article  CAS  PubMed  Google Scholar 

  30. Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes. 1997;46(2):313–6.

    Article  CAS  PubMed  Google Scholar 

  31. Kieffer TJ, Heller RS, Leech CA, Holz GG, Habener JF. Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes. 1997;46(6):1087–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Kulkarni RN, Wang ZL, Wang RM, Hurley JD, Smith DM, Ghatei MA, Withers DJ, Gardiner JV, Bailey CJ, Bloom SR. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest. 1997;100(11):2729–36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Ookuma M, Ookuma K, York DA. Effects of leptin on insulin secretion from isolated rat pancreatic islets. Diabetes. 1998;47(2):219–23.

    Article  CAS  PubMed  Google Scholar 

  34. Seufert J, Kieffer TJ, Leech CA, Holz GG, Moritz W, Ricordi C, Habener JF. Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. J Clin Endocrinol Metab. 1999;84(2):670–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Lupi R, Marchetti P, Maffei M, Del Guerra S, Benzi L, Marselli L, Bertacca A, Navalesi R. Effects of acute or prolonged exposure to human leptin on isolated human islet function. Biochem Biophys Res Commun. 1999;256(3):637–41.

    Article  CAS  PubMed  Google Scholar 

  36. Harvey J, McKenna F, Herson PS, Spanswick D, Ashford ML. Leptin activates ATP-sensitive potassium channels in the rat insulin-secreting cell line, CRI-G1. J Physiol. 1997;504(Pt 3):527–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Lam NT, Cheung AT, Riedel MJ, Light PE, Cheeseman CI, Kieffer TJ. Leptin reduces glucose transport and cellular ATP levels in INS-1 beta-cells. J Mol Endocrinol. 2004;32(2):415–24.

    Article  CAS  PubMed  Google Scholar 

  38. Covey SD, Wideman RD, McDonald C, Unniappan S, Huynh F, Asadi A, Speck M, Webber T, Chua SC, Kieffer TJ. The pancreatic beta cell is a key site for mediating the effects of leptin on glucose homeostasis. Cell Metab. 2006;4(4):291–302.

    Article  CAS  PubMed  Google Scholar 

  39. Kieffer TJ, Habener JF. The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol Endocrinol Metab. 2000;278(1):E1–14.

    CAS  PubMed  Google Scholar 

  40. Wang MY, Koyama K, Shimabukuro M, Newgard CB, Unger RH. OB-Rb gene transfer to leptin-resistant islets reverses diabetogenic phenotype. Proc Natl Acad Sci U S A. 1998;95(2):714–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Morioka T, Asilmaz E, Hu J, Dishinger JF, Kurpad AJ, Elias CF, Li H, Elmquist JK, Kennedy RT, Kulkarni RN. Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice. J Clin Invest. 2007;117(10):2860–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Holst JJ, Christensen M, Lund A, de Heer J, Svendsen B, Kielgast U, Knop FK. Regulation of glucagon secretion by incretins. Diabetes Obes Metab. 2011;13 Suppl 1:89–94.

    Article  CAS  PubMed  Google Scholar 

  43. Tudurí E, Marroquí L, Soriano S, Ropero AB, Batista TM, Piquer S, López-Boado MA, Carneiro EM, Gomis R, Nadal A, Quesada I. Inhibitory effects of leptin on pancreatic alpha-cell function. Diabetes. 2009;58(7):1616–24.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Chen L, Philippe J, Unger RH. Glucagon responses of isolated α cells to glucose, insulin, somatostatin, and leptin. Endocr Pract. 2011;17(5):819–25.

    Article  PubMed  Google Scholar 

  45. Lam CK, Chari M, Lam TK. CNS regulation of glucose homeostasis. Physiology (Bethesda). 2009;24:159–70.

    Article  CAS  Google Scholar 

  46. Grayson BE, Seeley RJ, Sandoval DA. Wired on sugar: the role of the CNS in the regulation of glucose homeostasis. Nat Rev Neurosci. 2013;14(1):24–37.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 1997;389:374–7.

    Article  CAS  PubMed  Google Scholar 

  48. Liu L, Karkanias GB, Morales JC, Hawkins M, Barzilai N, Wang J, Rossetti L. Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes. J Biol Chem. 1998;273:31160–7.

    Article  CAS  PubMed  Google Scholar 

  49. Cusin I, Zakrzewska KE, Boss O, Muzzin P, Giacobino JP, Ricquier D, Jeanrenaud B, Rohner-Jeanrenaud F. Chronic central leptin infusion enhances insulin-stimulated glucose metabolism and favors the expression of uncoupling proteins. Diabetes. 1998;47:1014–9.

    Article  CAS  PubMed  Google Scholar 

  50. van den Hoek AM, Teusink B, Voshol PJ, Havekes LM, Romijn JA, Pijl H. Leptin deficiency per se dictates body composition and insulin action in ob/ob mice. J Neuroendocrinol. 2008;20(1):120–7.

    Article  PubMed  Google Scholar 

  51. Minokoshi Y, Haque MS, Shimazu T. Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats. Diabetes. 1999;48(2):287–91.

    Article  CAS  PubMed  Google Scholar 

  52. Haque MS, Minokoshi Y, Hamai M, Iwai M, Horiuchi M, Shimazu T. Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes. 1999;48(9):1706–12.

    Article  CAS  PubMed  Google Scholar 

  53. Ueno N, Inui A, Kalra PS, Kalra SP. Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice. Peptides. 2006;27:2332–42.

    Article  CAS  PubMed  Google Scholar 

  54. German JP, Thaler JP, Wisse BE, Oh-I S, Sarruf DA, Matsen ME, Fischer JD, Taborsky Jr GJ, Schwartz MW, Morton GJ. Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology. 2011;152(2):394–404.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Coppari R, Ichinose M, Lee CE, Pullen AE, Kenny CD, McGovern RA, Tang V, Liu SM, Ludwig T, Chua Jr SC, Lowell BB, Elmquist JK. The hypothalamic arcuate nucleus: a key site for mediating leptin’s effects on glucose homeostasis and locomotor activity. Cell Metab. 2005;1(1):63–72.

    Article  CAS  PubMed  Google Scholar 

  56. Morton GJ, Gelling RW, Niswender KD, Morrison CD, Rhodes CJ, Schwartz MW. Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab. 2005;2(6):411–20.

    Article  CAS  PubMed  Google Scholar 

  57. Huo L, Gamber K, Greeley S, Silva J, Huntoon N, Leng XH, Bjørbaek C. Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab. 2009;9(6):537–47.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Berglund ED, Vianna CR, Donato Jr J, Kim MH, Chuang JC, Lee CE, Lauzon DA, Lin P, Brule LJ, Scott MM, Coppari R, Elmquist JK. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest. 2012;122(3):1000–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Gallardo N, Bonzón-Kulichenko E, Fernández-Agulló T, Moltó E, Gómez-Alonso S, Blanco P, Carrascosa JM, Ros M, Andrés A. Tissue-specific effects of central leptin on the expression of genes involved in lipid metabolism in liver and white adipose tissue. Endocrinology. 2007;148(12):5604–10.

    Article  CAS  PubMed  Google Scholar 

  60. Prieur X, Tung YC, Griffin JL, Farooqi IS, O’Rahilly S, Coll AP. Leptin regulates peripheral lipid metabolism primarily through central effects on food intake. Endocrinology. 2008;149(11):5432–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Warne JP, Alemi F, Reed AS, Varonin JM, Chan H, Piper ML, Mullin ME, Myers Jr MG, Corvera CU, Xu AW. Impairment of central leptin-mediated PI3K signaling manifested as hepatic steatosis independent of hyperphagia and obesity. Cell Metab. 2011;14(6):791–803.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Chong AY, Lupsa BC, Cochran EK, Gorden P. Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia. 2010;53(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  63. Oral EA, Chan JL. Rationale for leptin-replacement therapy for severe lipodystrophy. Endocr Pract. 2010;16(2):324–33.

    Article  PubMed  Google Scholar 

  64. Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401(6748):73–6.

    Article  CAS  PubMed  Google Scholar 

  65. Gavrilova O, Marcus-Samuels B, Leon LR, Vinson C, Reitman ML. Leptin and diabetes in lipoatrophic mice. Nature. 2000;403(6772):850.

    CAS  PubMed  Google Scholar 

  66. Asilmaz E, Cohen P, Miyazaki M, Dobrzyn P, Ueki K, Fayzikhodjaeva G, Soukas AA, Kahn CR, Ntambi JM, Socci ND, Friedman JM. Site and mechanism of leptin action in a rodent form of congenital lipodystrophy. J Clin Invest. 2004;113(3):414–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Miyamoto L, Ebihara K, Kusakabe T, Aotani D, Yamamoto-Kataoka S, Sakai T, Aizawa-Abe M, Yamamoto Y, Fujikura J, Hayashi T, Hosoda K, Nakao K. Leptin activates hepatic 5′-AMP-activated protein kinase through sympathetic nervous system and α1-adrenergic receptor: a potential mechanism for improvement of fatty liver in lipodystrophy by leptin. J Biol Chem. 2012;287(48):40441–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Savage DB, O’Rahilly S. Leptin therapy in lipodystrophy. Diabetologia. 2010;53(1):7–9.

    Article  CAS  PubMed  Google Scholar 

  69. Havel PJ, Uriu-Hare JY, Liu T, Stanhope KL, Stern JS, Keen CL, Ahrén B. Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin. Am J Physiol. 1998;274(5 Pt 2):R1482–91.

    CAS  PubMed  Google Scholar 

  70. Kiess W, Anil M, Blum WF, Englaro P, Juul A, Attanasio A, Dötsch J, Rascher W. Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index. Eur J Endocrinol. 1998;138(5):501–9.

    Article  CAS  PubMed  Google Scholar 

  71. Yu X, Park BH, Wang MY, Wang ZV, Unger RH. Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci U S A. 2008;105(37):14070–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Chinookoswong N, Wang JL, Shi ZQ. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes. 1999;48(7):1487–92.

    Article  CAS  PubMed  Google Scholar 

  73. Lin CY, Higginbotham DA, Judd RL, White BD. Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab. 2002;282(5):E1084–91.

    CAS  PubMed  Google Scholar 

  74. Hidaka S, Yoshimatsu H, Kondou S, Tsuruta Y, Oka K, Noguchi H, Okamoto K, Sakino H, Teshima Y, Okeda T, Sakata T. Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats. FASEB J. 2002;16(6):509–18.

    Article  CAS  PubMed  Google Scholar 

  75. Kojima S, Asakawa A, Amitani H, Sakoguchi T, Ueno N, Inui A, Kalra SP. Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice. Peptides. 2009;30(5):962–6.

    Article  CAS  PubMed  Google Scholar 

  76. Fujikawa T, Berglund ED, Patel VR, Ramadori G, Vianna CR, Vong L, Thorel F, Chera S, Herrera PL, Lowell BB, Elmquist JK, Baldi P, Coppari R. Leptin engages a hypothalamic neurocircuitry to permit survival in the absence of insulin. Cell Metab. 2013;18(3):431–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Park JY, Chong AY, Cochran EK, Kleiner DE, Haller MJ, Schatz DA, Gorden P. Type 1 diabetes associated with acquired generalized lipodystrophy and insulin resistance: the effect of long-term leptin therapy. J Clin Endocrinol Metab. 2008;93(1):26–31.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Guo K, McMinn JE, Ludwig T, Yu YH, Yang G, Chen L, Loh D, Li C, Chua Jr S, Zhang Y. Disruption of peripheral leptin signaling in mice results in hyperleptinemia without associated metabolic abnormalities. Endocrinology. 2007;148(8):3987–97.

    Article  CAS  PubMed  Google Scholar 

  79. Huynh FK, Levi J, Denroche HC, Gray SL, Voshol PJ, Neumann UH, Speck M, Chua SC, Covey SD, Kieffer TJ. Disruption of hepatic leptin signaling protects mice from age- and diet-related glucose intolerance. Diabetes. 2010;59(12):3032–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis, IN, 46202, USA

    Rachel C. Morgan M.D.

  2. Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Robert V. Considine Ph.D.

Authors
  1. Rachel C. Morgan M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert V. Considine Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert V. Considine Ph.D. .

Editor information

Editors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Sam Dagogo-Jack, MD

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Morgan, R.C., Considine, R.V. (2015). Leptin and Intermediary Metabolism: Focus on Glucoregulation and Lipids. In: Dagogo-Jack, MD, S. (eds) Leptin. Springer, Cham. https://doi.org/10.1007/978-3-319-09915-6_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-09915-6_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-09914-9

  • Online ISBN: 978-3-319-09915-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation