LAPORAN PENELITIAN HIBAH BERSAING

TAHUN ANGGARAN 2011

PROFILIN SEBAGAI BIOMARKER DISFUNGSI ADIPOSIT (STUDI HUBUNGAN

DISFUNGSI ADIPOSIT DENGAN INFEKSI Toxoplasma gondii

PADA INDIVIDU OBESE)

o leh:

dr. Agustin Iskandar, MKes

Prof.DR.dr. M Rasyad Indra, MS

Satuman,S.Si, MKes

Dib iayai O leh Dire ktorat Jenderal P endidika n Tinggi, Kementrian Pendidikan Nasional,

melalui DIPA Univers itas Brawijaya Rev.1 Nomor : 0636/023-04.2.16/15/20 11 R, tanggal

30 Mare t 2011, dan berda sarkan Surat dari DP2M Dikt i Nomor: 121/D3/PL/2011

tanggal 7 Februari 2011

UNIVERSITAS BRAWIJAYA

NOPEM BER 2011

KESEHATAN

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 profilin-

like 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 IL-

12 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 IL-

12 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 MyD88-

pathway.

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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