Adipokines: a new view of adipose tissue

Authors

  • Daniella Esteves Duque GUIMARÃES Universidade Federal do Rio de Janeiro
  • Fátima Lúcia de Carvalho SARDINHA Universidade Federal do Rio de Janeiro
  • Daniella de Moraes MIZURINI Universidade Federal do Rio de Janeiro
  • Maria das Graças TAVARES DO CARMO Universidade Federal do Rio de Janeiro

Keywords:

adipokines, atherosclerosis, obesity, insulin resistance, adipose tissue

Abstract

Leptin is a hormone secreted by adipocytes whose effect on the sympathetic nervous system and endocrine function confers active participation in the control of energy expenditure and appetite. Its identification added to the fat tissues in the human body the role of a multifunctional organ that produces and secretes a number of bioactive peptides and proteins, called adipocytokines. Changes in the amount of fat tissue, such as the ones that occur in obesity, affect the production of most of these factors secreted by adipocytes. Even if these changes are frequently associated with many metabolic disorders and increased risk for cardiovascular
diseases, the role of fat tissue in the development of these complications, considered its endocrine function, continue to be investigated. The concentration of various adipocytokines increase in obesity and have been associated with hypertension (angiotensinogen), fibrinolysis impairment (plasminogen activator inhibitor-1) and insulin resistance (protein that stimulates acylation, tumor necrosis factor-alpha, interleukine-6 and resistin). On the other hand, leptin and adiponectin affect insulin sensitivity. In obesity, insulin resistance is also associated with leptin resistance and reduced plasma levels of adiponectin. Leptin and adiponectin still have complementary and distinct organic functions: adiponectin has potent antiatherogenic activity while
leptin participates in the control of food intake. Some medications used to control diabetes increase adiponectin production in rodents and humans, suggesting that the development of new medications that target the adipocytokines can represent a new therapeutic alternative to prevent insulin resistance and atherosclerosis in obese individuals.

References

Havel PJ. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes. 2004; 53(Suppl 1): S143-51.

Hauner H. The new concept of adipose tissue function. Physiol Behav. 2004; 83(4):653-8.

Dusserre E, Moulin P, Vidal H. Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. Biochim Biophys Acta. 2000; 1500(1):88-96.

Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995; 269(5223):543-6.

Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997; 387(6636): 903-8.

Maffei M, Stoffel M, Barone M, Moon B, Dammerman M, Ravussin E, et al. Absence of mutations in the human OB gene in obese/diabetic subjects. Diabetes. 1996; 45(5):679-82.

Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, 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.

Kalra SP. Circumventing leptin resistance for weight control. Proc Natl Acad Sci USA. 2001; 98(8): 4279-81.

Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, 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.

Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 1996; 348(9021):159-61.

Ahima RS, Flier JS. Leptin. Ann Rev Physiol. 2000; 62:413-37.

Cioffi JA, Shafer AW, Zupancic TJ, Smith-Gbur J, Mikhail A, Platika D, et al. Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat Med. 1996; 2(5):585-9.

Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, et al. Biological action of leptin as an angiogenic factor. Science. 1998; 281(5383):1683-6.

Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998; 394(6696): 897-901.

Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000; 100(2):197-207.

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(5223): 546-9.

Schwartz MW, Baskin DG, Bukowski TR, Kuijper JL, Foster D, Lasser G, et al. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes. 1996; 45(4):531-5.

Muzumdar R, Ma X, Yang X, Atzmon G, Bernstein J, Karkanias G, et al. Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms FASEB J. 2003; 17(9):1130-2.

Seufert J, Kieffer TJ, Leech CA, Holz GG, Moritz W, Ricordi C, et al. 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.

Ahren B, Havel PJ. Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line (INS-1 cells). Am J Physiol. 1999; 277(4 Pt 2): R959-66.

Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M, Cinti S, et al. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes. 2002; 51(1):144-51.

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.

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(9):2332-42.

Ogawa Y, Masuzaki H, Hosoda K, Aizawa-Abe M, Suga J, Suda M, et al. Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin. Diabetes. 1999; 48(9):1822-9.

Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998; 392(6674):398-401.

Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999; 100(25): 2473-6.

Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003; 361(9353):226-8.

Goldstein BJ, Scalia R. Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab. 2004; 89(6):2563-8.

Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005; 115(5):911-9.

Funahashi T, Matsuzawa Y, Kihara S. Adiponectin as a potential key player in metabolic syndrome Insights into atherosclerosis, diabetes and cancer. Int Congress Series. 2004; 1262:368-71.

Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003; 9(15):5699-704.

Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002; 8(11):1288-95.

Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409(6818): 307-12.

Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, et al. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001; 50(10):2199-202.

Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM. Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res. 2002; 10(1):1-5.

Gomez-Ambrosi J, Fruhbeck G. Do resistin and resistin-like molecules also link obesity to inflammatory diseases? Ann Intern Med. 2001; 135(4):306-7.

Cianflone K, Xia Z, Chen LY. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta. 2003; 1609(2):127-43.

Maslowska M, Scantlebury T, Germinario R, Cianflone K. Acute in vitro production of acylation stimulating protein in differentiated human adipocytes. J Lipid Res. 1997; 38(1):1-11.

Scantlebury T, Maslowska M, Cianflone K. Chylomicron-specific enhancement of acylation stimulating protein and precursor protein C3 production in differentiated human adipocytes. J Biol Chem. 1998; 273(33):20903-9.

Comuzzie AG, Cianflone K, Martin LJ, Zakarian R, Nagrani G, Almasy L, et al. Serum levels of acylation stimulating protein (ASP) show evidence of a pleiotropic relationship with total cholesterol, LDL, and triglycerides and preliminary evidence of

linkage on chromosomes 5 and 17 in Mexican Americans. Obes Res. 2001; 9:103S.

Murray I, Havel PJ, Sniderman AD, Cianflone K. Reduced body weight, adipose tissue, and leptin levels despite increased energy intake in female mice lacking acylation-stimulating protein. Endocrinology. 2000; 141(3):1041-9.

Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc. 2001; 60(3):349-56.

Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab. 2001; 280(6):E827-47.

Morin CL, Eckel RH, Marcel T, Pagliassotti MJ. High fat diets elevate adipose tissue-derived tumor necrosis factor-alpha activity. Endocrinology. 1997; 138(11):4665-71.

Ruan H, Miles PD, Ladd CM, Ross K, Golub TR, Olefsky JM, et al. Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: implications for insulin resistance. Diabetes. 2002; 51(11): 3176-88.

Van Snick J. Interleukin-6: an overview. Ann Rev Immunol. 1996; 8:253-78.

Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998; 83(3):847-50.

Nonogaki K, Fuller GM, Fuentes NL, Moser AH, Staprans I, Grunfeld C, et al. Interleukin-6 stimulates hepatic triglyceride secretion in rats. Endocrinology. 1995; 136(5):2143-9.

Haddy N, Sass C, Droesch S, Zaiou M, Siest G, Ponthieux A, et al. IL-6, TNF-alpha and atherosclerosis risk indicators in a healthy family population: the STANISLAS cohort. Atherosclerosis. 2003; 170(2):277-83.

Wallenius K, Wallenius V, Sunter D, Dickson SL, Jansson JO. Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun. 2002; 293(1):560-5.

Juhan-Vague I, Alessi MC. PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost. 1997; 78(1):656-60.

Bastelica D, Morange P, Berthet B, Borghi H, Lacroix O, Grino M, et al. Stromal cells are the main plasminogen activator inhibitor-1-producing cells in human fat: evidence of differences between visceral and subcutaneous deposits. Arterioscler Thromb Vasc Biol. 2002; 22(1):173-8.

Samad F, Loskutoff DJ. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol Med. 1996; 2(5):568-82.

Birgel M, Gottschling-Zeller H, Rohrig K, Hauner H. Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes. Arterioscler Thromb Vasc Biol. 2000; 20(6):1682-7.

Crandall DL, Busler DE, McHendry-Rinde B, Groeling TM, Kral JG. Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1. J Clin Endocrinol Metab. 2000; 85(7):2609-14.

Schafer K, Fujisawa K, Konstantinides S, Loskutoff DJ. Disruption of the plasminogen activator inhibitor 1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob/ob mice. FASEB J. 2001; 15(10):1840-2.

Massiera F, Bloch-Faure M, Ceiler D, Murakami K, Fukamizu A, Gasc JM, et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J. 2001; 15(14):2727-9.

Einstein FH, Atzmon G, Yang XM, Ma XH, Rincon M, Rudin E, et al. Differential responses of visceral and subcutaneous fat depots to nutrients. Diabetes. 2005; 54(3):672-8.

Ailhaud G, Fukamizu A, Massiera F, Negrel R, SaintMarc P, Teboul M. Angiotensinogen, angiotensin II and adipose tissue development. Int J Obes Relat Metab Disord. 2000; 24(Suppl 4):S33-5.

Darimont C, Vassaux G, Ailhaud G, Negrel R. Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin-II. Endocrinology. 1994; 135(5): 2030-6.

Published

2023-09-15

How to Cite

Duque GUIMARÃES, D. E. ., de Carvalho SARDINHA, F. L., de Moraes MIZURINI, D., & TAVARES DO CARMO, M. das G. (2023). Adipokines: a new view of adipose tissue. Brazilian Journal of Nutrition, 20(5). Retrieved from https://periodicos.puc-campinas.edu.br/nutricao/article/view/9711