Leptin was discovered in 1994, finding, that marked the beginning of a new understanding about white adipose tissue. Up to end of 20th century this tissue was viewed as an inert tissue, devoted to body protection from heat loss and to passively store energy. This static vision, changed with identification of the product of the gene obese (ob) wich accentuated the role of adipose tissue in the physiopathology of obesity-linked diseases, and led to the discovery of various adipokines, many of a pro-inflammatory nature. With emerged knowledge of (WAT)-derived adipokines, it is obvious that they can be now considered as the bond between obesity-related environmental causes, such as nutrition and lifestyle, and the biochemical shifts that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. This paper deals with reviews of recent adipokine research, with particular emphasis to the role of leptin, adiponectin, resistin, and visfatin in chondrocyte function and skeleton, as well as in inflammatory and degenerative cartilage joint diseases.
Otero M, Lago R, Lago F, Reino JJ, Gualillo O. Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1. Arthritis Res Ther. 7.
2.
Lago R, Gomez R, Otero M, Lago F, Gallego R, Dieguez C, et al. A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarthritis Cartilage. 16:1101–9.
3.
Lee SW, Kim JH, Park MC, Park YB, Lee SK. Adiponectin mitigates the severity of arthritis in mice with collagen-induced arthritis. Scand J Rheumatol. 37:260–8.
4.
Matarese G, Leiter EH, Cava A. Leptin in autoimmunity: many questions, some answers. Tissue Antigens. 70:87–95.
5.
Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 50:2094–9.
6.
Matsuzawa Y. Therapy Insight: adipocytokines in metabolic syndrome and related cardiovascular disease. Nat Clin Pract Cardiovasc Med. 3:35–42.
7.
Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol. 178:1748–58.
8.
Otero M, Gomez Reino JJ, Gualillo O. Synergistic induction of nitric oxide synthase type II: in vitro effect of leptin and interferon-gamma in human chondrocytes and ATDC5 chondrogenic cells. Arthritis Rheum. 48:404–9.
9.
Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gomez-Reino JJ, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin, and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis. 65:1198–201.
10.
Otero M, Lago R, Lago F, Casanueva FF, Dieguez C, Gomez-Reino JJ, et al. Leptin, from fat to inflammation: old questions and new insights. FEBS Lett. 579:295–301.
11.
Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation. 111:932–9.
12.
13.
Gomez R. Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases.
14.
Simopoulous T, Malizos KN, Iliopoulos D, Stefanou N, Papatheodorou L, Ioannou M, et al. Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthritis Cartilage. 15:872–83.
15.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 409:307–12.
16.
Takeda S, Karsenty G. Molecular bases of the sympathetic regulation of bone mass. Bone. 42:837–40.
17.
Teichtahl AJ, Wluka AE, Proietto J, Cicuttini FM. Obesity and the female sex: risk factors for knee osteoarthritis that may be attributable to systemic or local leptin biosynthesis and its cellular effects. Med Hypotheses. 65:312–5.
18.
Tong KM, Shieh DC, Chen CP, Tzeng CY, Wang SP, Huang KC, et al. Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K.
Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nature.
21.
Fraser DA, Thoen J, Reseland JE, Forre O, Kjeldsen-Kragh J. Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation. Clin Rheumatol. 18:394–401.
22.
A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Cartilage. 16:1101–9.
23.
Bernotiene E, Palmer G, Gabay C. The role of leptin in innate and adaptive immune responses. Arthritis Res Ther. 8(217).
24.
Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A. Resistin, an adipokine with potent proinflammatory properties. J Immunol. 174:5789–95.
25.
Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, et al. Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum.
26.
Bokarewa M, Bokarew D, Hultgren O, Tarkowski A. Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis. 62:952–6.
27.
Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 48:3118–29.
28.
Gualillo O, Eiras S, Lago F, Dieguez C, Casanueva FF. Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sci. 67:2433–41.
29.
Faggioni R, Feingold KR, Grunfeld C. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J. 15:2565–71.
30.
Fruhbeck G. Intracellular signalling pathways activated by leptin. Biochem J. 393:7–20.
31.
Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 382:250–2.
32.
Gualillo O. Further evidence for leptin involvement in cartilage homeostasis. Osteoarthritis Cartilage. 15:857–60.
33.
Ehling A, Schaffler A, Herfarth H, Tarner IH, Anders S, Distler O, et al. The potential of adiponectin in driving arthritis. J Immunol. 176:4468–78.
34.
Fantuzzi G. Adiponectin and inflammation: consensus and controversy. J Allergy Clin Immunol. 121:326–30.
35.
Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 307:426–30.
36.
Gosset M, Berenbaum F, Salvat C, Sautet A, Pigenet A, Tahiri K, et al. Crucial role of visfatin/pre-B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum. 58:1399–409.
37.
Harsch IA, Koebnick C, Wallaschofski H, Schahin SP, Hahn EG, Ficker JH, et al. Resistin levels in patients with obstructive sleep apnoea syndrome--the link to subclinical inflammation? Med Sci Monit. 10.
38.
39.
Iliopoulos D, Malizos KN, Tsezou A. Epigenetic regulation of leptin affects MMP.
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