Adipose tissue secretes bioactive peptides, termed 'adipokines', which act locally and distally through autocrine, paracrine and endocrine signals. Those signals influences the answers of other tissues and organs including hypothalamus, pancreas, liver, sceletal muscles, endotel an immune system. Increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Leptin is a critical mediatorof energy balance that relays information regarding the depletion or accumulation of fat stores to the brain. Althoughmany of leptin's effects result rb from a direct action ofleptin on hypothalamic neurons, the functional leptin receptor(long-form or lep ) is also found on many tissues outside the central nervous system (CNS), including immune cells. Obese individuals seem to be resistantto the hypothalamic effects of leptin (maybe because of defective blood-brain barrier transport), the catabolic pathways designed to reduce appetite and increase energy expenditure are not activated and excess body weight is maintained). Adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Adiponectin and resistin are adipocyte-derived polypeptide hormones playing a role in metabolic homeostasis. Their plasma levels are inversely (adiponectin) or directly (resistin) correlated to obesity (and in a patients with type 2 diabetes mellitus) and they have opposite effects on insulin sensitivity. Adipocytes secretes also adipsin, factor B and factor C. In-depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies
M.J. L, R.Z. Y, Y. W, K. K, E. B, P. M, et al. Plasma resistin levels are inversely correlated with insulin sensitivity. J Clin Endocrinol Metab. 89:4738–45.
2.
T. Y, J. K, H. W. The fat cell-specific protein adiponectin improves glucose metabolism and insulin resistance. Nat Med. 7:941–6.
3.
T.W. J, M.S. K, J.H. K, H.S C. Adipokines and insulin resistance. Korean J Intern Med. 20:109–14.
4.
I.I. S, J.L. F, R.K M. Leptin resistance and insulin sensitivity: implications for treatment. Diabetes Obes Metab. 8:555–64.
5.
6.
C.D M. Leptin signaling in brain: role in the regulation of food intake and energy balance. Am J Physiol Regul Integr Comp Physiol. :284.
7.
K.J. G, R. B, K.J R. The role of leptin in obesity and metabolic syndrome. Clin Chem. 51:1338–45.
8.
J.M F. Leptin and the regulation of body weight. Harv Rev Psychiatry. 10:245–50.
9.
J. D, H W. Resistin: a potential therapeutic target in obesity. Future Med Chem. 4:1557–68.
10.
J.P. B, M. M, Nhieu J.T. Adipocyte-secreted cytokines: production and secretion of tumor necrosis factor-α, interleukin-6, and leptin in obese and non-obese subjects. J Clin Endocrinol Metab. 87:1041–9.
11.
J.I. RB, A. M, J.A M. Insulin resistance and obesity: the role of resistin. World J Gastroenterol. 11:7243–9.
12.
T.J. Z, P.D. L, M. E, J. P, C. W, A. K, et al. Receptor for resistin and resistin resistance in obesity. J Biol Chem. 280:3043–55.
13.
Cava A., G M. The weight of leptin in immunity. Nat Rev Immunol. 4:371–9.
14.
K. C, S T. Insulin resistance and metabolic syndrome: an update. J Diabetes Complications. 18:201–9.
15.
S. H, E. F, J. K, Y S. Measurement of leptin and its relation to obesity and metabolic syndrome. Metabolism. 54:288–94.
16.
D.R. M, J.P. H, A.S. R, B.A. N, P.D. S, J.S. C, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28:412–9.
17.
C.M. G, D. C, H.L. L, M.T. S, S. T, T B. The role of leptin in the pathogenesis of obesity and related diseases. J Endocrinol. 186:171–83.
18.
L.A T. The leptin receptor. J Biol Chem. 272:6093–6.
19.
M. S, R. M, H D. Resistin and its effects on glucose and lipid metabolism. J Lipid Res. 46:225–37.
20.
C. B, B.B K. Leptin signaling in the central nervous system and the periphery. Curr Opin Neurobiol. 14:583–90.
21.
B.E. G, S. K, R.W. G. Leptin resistance and its implications for obesity. J Endocrinol. 185:317–30.
22.
H.E. L, R.A D. The role of adipose tissue in insulin resistance. J Endocrinol. 177:291–6.
23.
J. V, I. J, M. K. Adipokines and insulin resistance in obesity: a review. Biochem Med. 15:117–29.
24.
M.H. L, Y. W, E. S. Insulin resistance and leptin resistance in obese patients: A review. Horm Metab Res. 38:69–75.
25.
J.H. K, Y.J. P, W.S. C. Leptin resistance and its effects on insulin resistance and lipid metabolism. Exp Diabetes Res. 5:365–72.
26.
X. F, L. Z, W J. The role of leptin in obesity and insulin resistance. Chin Med J. 119:1636–43.
27.
D. K, M. W, S. D. The role of adipose tissue in the development of insulin resistance. J Physiol Pharmacol. 55:71–84.
28.
J.G. K, A. BW, M.J M. Role of adipose tissue in energy homeostasis and obesity. Eur J Clin Nutr. 60:4–9.
29.
B.H. G, R. T, J. H, D.E K. Obesity and insulin resistance: the role of insulin action in adipose tissue. J Clin Endocrinol Metab. 88:240–8.
30.
K. G, J. L, T. M. The role of resistin in obesity and insulin resistance. Diabetes Metab Res Rev. 21:172–9.
31.
D. S, J. W, Z. W. Adiponectin: a review of its role in metabolism and cardiovascular disease. Diabetes Obes Metab. 8:1045–52.
32.
S. H, J. C, M. H, J R. Resistin: a potential link between obesity and insulin resistance. Eur J Endocrinol. 151:145–52.
33.
A. R, A. M, C. R, J.M. G, J.A. S, J.M H. Leptin and insulin sensitivity in obesity: role of resistin. Int J Obes. 28:190–8.
34.
C.D M. Adipose tissue and leptin. J Clin Endocrinol Metab. 86:2465–71.
35.
J.M. F, J.L H. Leptin and its role in the regulation of body weight. J Clin Invest. 100:1114–21.
36.
Webber J. Energy balance in obesity. Proc Nutr Soc. 62:539–43.
37.
M.M. V, C.P L. Leptin: from animals to humans. Curr Pharm Des. 9:811–8.
38.
T. G. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A. 93:14564–8.
39.
T. R, G. L, E M. The Endocrine Function of Adipose Tissue: An Update. Clin Endocrinol. 64(4):355–65.
40.
H. F, T. Y, R. S, S S. Distribution, function, and properties of leptin receptors in the brain. Int Rev Cytol. 224:1–27.
41.
A.M W. Measurement of leptin and leptin binding in the human circulation. Ann Clin Biochem. 37:244–52.
42.
P. T, N. H, J.G. M, D.V R. Leptin: fundamental aspects. Int J Obes Relat Met Disord. 23:22–8.
43.
P.C. T, V. P, S.A. R, C T. Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin’s actions. Metabolism. 49:1537–41.
44.
M.W. S. Central nervous system control of food intake. Nature. 404:661–71.
45.
Magni P. Hormonal control of the neuropeptide Y system. Curr Protein Pept Sci. 4:45–57.
46.
Baratta M. Leptin: from a signal of adiposity to a hormone mediator in peripheral tissues. Med Sci Monit. 8:282–92.
47.
J.M. F, J.L H. Leptin and the regulation of body weight in mammals. Nature. 22:763–70.
48.
Zhang Y. Positional cloning of the mouse obese gene and its human homologue. Nature (London. 372:425–32.
49.
P.K S. Adipose tissue as a source of hormones. Am J Clin Nutr. 45:277–82.
50.
K. A, N. G, C. R, M. E, Y. G, P A. A nitric oxide-mediated mechanism regulates lipolysis in human adipose tissue in vivo. Br J Pharmacol. 126:1639–45.
51.
S. K, N MM. Secretory, endocrine and autocrine/paracrine function of the adipocyte. J Nutr. 130(3110).
52.
Diamond F. The endocrine function of adipose tissue. Growth Genet Horm. 18:17–23.
53.
W.F. B, A. J. Reference ranges of serum leptin. In: Leptin: The Voice of Adipose Tissue. p. 318–26.
54.
H. C, K. G, J. M. Adipocyte-secreted factors and insulin resistance. Arterioscler Thromb Vasc Biol. 24:1240–8.
55.
C. O, J.M. O, D. S. Expression of leptin and leptin receptor during the development of liver fibrosis and cirrhosis. In: *Exp Clin Endocrinol Diabetes.
56.
T. P, F. V, A. AM. The severity of liver fibrosis is associated with high leptin levels in chronic hepatitis C. J Viral Hepat. 11:91–6.
57.
E.A. O, V. S, E. R, A. A, A. P, P. S, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 346:570–8.
58.
59.
P.J H. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes. 53(Suppl 1).
60.
D. K, Z. G, C.L. F, D. M, S.A T. The involvement of the blood-brain and the blood-cerebrospinal fluid barriers in the distribution of leptin into and out of the rat brain. Neuroscience. 123:527–36.
61.
S.M. G, V.D. C, C.S M. Energy homeostasis, obesity and eating disorders: recent advances in endocrinology. J Nutr. 134:295–8.
62.
E.E. K, J.S F. Adipose Tissue as an Endocrine Organ. J Clin Endocrinol Metab. 89(6):2548–64.
63.
M.K. S, J.P. O, M.L. H, A. K, T.W. S, S. M, et al. Nocturnal rise of leptin in lean, obese, and non-insulin dependent diabetes mellitus subjects. J Clin Invest. 97:1344–7.
64.
L.J. S, K.W. S, P.L. S, A. K, Quier F., J. M, et al. Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem. 271:5301–4.
65.
66.
R.L L. The role of leptin in the control of body weight. Nutr Rev. :60.
67.
68.
P. K, B. C, M.L. J, A. D, S G. Characterization of leptin pulse dynamics and relationship to fat mass, growth hormone, cortisol, and insulin. Am J Physiol Endocrinol Metab. :285.
69.
Adamo D. Increased OB gene expression leads to elevated plasma leptin concentrations in patients with chronic primary hyperinsulinemia. Diabetes. 47:1625–9.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.
