KES EHAT AN
LAPORAN PENELITIAN HIBAH BERSAING TAHUN ANGG ARAN 2011
PR OFILIN SEB AG AI B IOM A RK ER D ISFU N GSI AD IPOSIT (STU DI H UB U NG AN D ISF UN GSI A DIPO SIT DEN G AN IN FEK SI T ox oplas m a gon dii P AD A IND IVI DU O BESE)
o le h : d r. Ag u stin Iska nd a r, M Ke s Prof.D R. dr. M R a sya d In d ra, M S Sat um a n ,S.Si, M Kes
D ib iay ai O leh Dire ktorat J enderal P endidika n T inggi, Kementrian Pendidik an N asional, melalui DIPA Univers itas Brawijaya R ev .1 Nomor : 0636/ 023-04.2.16/15/20 11 R , tanggal 30 Mare t 2011, dan berda sarkan Surat dari DP2M Dikt i N omor: 121/D3/ PL/2011 tanggal 7 F ebruari 2011
U NIVE R SITA S B RA W IJA Y A N OP EM BE R 2011
RINGKASAN Sindroma metabolik merupakan kumpulan beberapa faktor resiko seperti hipertensi, dislipidemia, gangguan toleransi glukosa dan obesitas. Sindroma ini memiliki hubungan dengan mekanisme patologis penyakit kardiovaskuler. Obesitas yang menjadi faktor resiko sindroma metabolik pada umumnya obesitas abdominal atau obesitas viseral. Prevalensi obesitas di seluruh dunia dan hubungannya dengan kelompok penyakit metabolik meningkat dengan cepat. Di Amerika Serikat 65,7% dewasa dan 16% anak-anak mengalami overweight (Tuncman, et al., 2006; http://www.americanheart.org). Angka obesitas terus meningkat dari tahun ke tahun. Laporan WHO tahun 2003 menyebutkan, di dunia lebih dari 300 juta orang dewasa menderita obesitas. Di Amerika 280.000 orang meninggal setiap tahunnya akibat obesitas karena menjadi pemicu penyakit-penyakit seperti jantung, artritis, DM tipe 2 serta tekanan darah tinggi (Rajala, et al., 2003). Sampai saat ini peranan infeksi profilin dari parasit T. gondii dalam hubungannya dengan disfungsi adiposit belum banyak diketahui. Toxoplasma gondii merupakan parasit patogen intraseluler yang memiliki kemampuan untuk menginfeksi semua sel berinti mamalia (Olgica D and Vladimir M, 2001). T gondii memiliki molekul profilin yang berhubungan dengan infeksi pada sel host melalui aktivasi TLRs. Penelitian yang dilakukan Sudjari, dkk. (2009) memperoleh hasil bahwa; (1) paparan profilin T.gondii pada kultur sel lemak subkutan dapat meningkatkan kadar IL-6 dan TNF-α serta menurunkan kadar TLR-11, dan (2) peningkatan kadar IL-6 dan TNF-α pada lemak subkutan mengindikasikan terjadinya adiposopati dan sindroma metabolik akibat infeksi profilin T.gondii. Penelitian ini bertujuan untuk mengetahui kadar profilin T gondii pada individu obese, dibandingakan dengan individu yang tidak obese, serta mengetahui hubungan antara kadar profilin T gondii dengan ekspresi IL-6 dan IL-12 pada individu obese. Dengan diketahuinya kadar profilin, IL-6 dan IL-12 pada individu obese, didapatkan gambaran keterlibatan disfungsi adiposit pada patomekanisme sindroma metabolik akibat infeksi protozoa parasit. Penelitian ini adalah penelitian observasional analitik dengan desain cross sectional study. Subyek dalam penelitian ini adalah 65 individu obese dan 10 individu sehat sebagai pembanding. Setelah melalui wawancara, dilakukan pemeriksaan antropometri dan panel sindroma metabolik. Pengukuran kadar profilin, IL-6 dan IL-12 dilakukan menggunakan metode ELISA. Hasil penelitian pada 65 individu obese didapatkan rerata kadar profilin yang berbeda bermakna bila dibandingkan dengan individu yang tidak obese (p= 0,001; α= 0,05). Hal ini
menunjukkan bahwa adanya infeksi oleh Toxoplasma gondii akan meningkatkan ekspresi profilin yang dibutuhkan untuk invasi parasit pada sel host, termasuk sel lemak. Ikatan profilinlike protein dengan TLR-11 selanjutnya akan meningkatkan ekspresi sitokin proinflamasi yang berakibat meningkatnya inflamasi pada adiposit sehingga timbul adipositopati dan obesity. Hasil yang seiring ditunjukkan oleh IL-12, yakni terdapat perbedaan kadar IL-12 yang bermakna antara individu obese dengan individu sehat(p=0,001, α=0,05). Hal ini dapat terjadi karena pada individu obese, terjadi peningkatan ekspresi adipositokin termasuk IL-12 sebagai sitokin proinflamasi. Hasil penelitian ini sejalan dengan peningkatan profilin yang bermakna pada individu obese. Adanya peningkatan ekspresi profilin akan meningkatkan ekspresi IL-12 sebagai akibat ikatan profilin dengan TLR-11 pada membran adiposit. Selanjutnya ikatan ini melalui MyD88-pathway akan merangsang ekspresi inflamatory cytokine termasuk IL-12. Hasil uji independent t test untuk rerata kadar IL-6 menunjukkan bahwa tidak terdapat perbedaan kadar IL-6 yang bermakna antara individu obese dengan individu sehat (p=0,068, α=0,05). Hal ini diduga disebabkan karena IL-6 bukan satu-satunya sitokin yang meningkat pada obesitas. Terdapat sitokin lain seperti TNF-α yang juga meningkat Penelitian lebih lanjut diperlukan untuk mengetahui hubungan antara peningkatan kadar profilin dengan adipositokin lain sehingga lebih bisa menjelaskan patomekanisme terjadinya disfungsi adiposit akibat infeksi parasit Toxoplasma gondii.
SUMMARY Metabolic syndrome (MetS) is a cluster of various clinicalcardiovascular risk factors including obesity, dyslipidemia and hypertension, and is characterized by high fasting circulating insulin levels. This syndrome have relationship with pathologic mechanism of cardiovascular diasease. Obesity, especially abdominal or visceral obesity is one of risk factor of metabolic syndrome. The prevalence of obesity and the relationship with metabolic syndrome is increase around the world. WHO reported that over 300 million of adult was suffer from obesity, and this will be increase year by year. The role of profilin infection by Toxoplasma gondii parasit in relation with adipocyt dysfunction is unclear until now. Toxoplasma gondii is intracelluler pathogenic parasit which able to infect all of nucleated cells, include adipocyte. T gondiihave profilin molecule which correlate with invasion to host cells by activating TLRs. Study by Sudjari et.al,showed that exposure with profilin of T.gondiiin sub cutaneous adipocyt cells can increase the level of IL-6 and TNF-α . This exposure can also decrease the level of TLR-11, so they conclude that increasing level of IL-6 and TNF-α in subcutaneous adipocyt indicate that there was adipocytopathy and metabollic syndrome as a result of profilin infection ofT.gondii. This study was conducted to know the level of Toxoplasma gondii profilin in obese patient, compared to healthy subject. This study also conducted to know the level of IL-6 and IL12 as inflammatory cytokine and to know the relationship between T gondii profilin and the level of IL-6 and IL-12 in obese patient. This study was observational analytic using cross sectional design. The subjects were 65 obese patients and 10 healthy patients. After some interview, the subjects were performed antropometric measurement and then performed metabolic syndrome panel. The level of profilin, IL-6 and IL-12 was performed by using ELISA method. The result showed that there was significant difference of provilin level in obese patients compared to healthy patients (p= 0,001; α= 0,05). This result show that infection by Toxoplasma gondiiwill increase profilin expression which needed to parasit invasion to host cell, including adipocyt cell. The binding of protein-like profilin of Toxoplasma gondii with TLRs followed by increasing inflammatory cytokine in adipocyt resulting adipositopathy and obesity. Similar result was shown for IL-12, in which significant difference of IL-12 level was noted between obese and healthy groups (p=0.001, α=0.05). This might occured becauseincreased expression of adipositokin, including IL-12, as one of proinflammatory cytokines in individu with obesity. This current result was appropiate to significant increase of
profilin in obese individu. Increased expression of profilin results in increased expression of IL12 as a consequence of profilin binding to TLR-11 on adipocyt membrane. Further more, this binding stimulate expressions of inflammatory cytokines, including IL-12, through MyD88pathway. Independent t test for mean of IL-6 level revealed no significant difference of IL-6 level between obese and healthy group(p=0.068, α=0.05). This is thought because that IL-6 is not only cytokine increased in obesity. Other cytokines such as TNF-α is also increased. Further research is needed to understand the relationship between increasing profilin level and other adipocytokines so that there will be more explainable pathomechanism of adipocyt dysfunction secondary to Toxoplasma gondii infection
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