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"TB is still major problem even though number of TB cases had been decline steadily due to discovery and continuing research of TB drugs since 1940 and also increasing of funding and attention to global TB problem. Indonesia is the third country in descending order of TB case numbers. It is considered as the third main cause of death after cardiovascular and respiratory diseases in this country. Several years ago, East Nusa Tenggara province had the highest incidence of sputum smear positive compared with other provinces in Indonesia. TB creates certain burdens in the community, initially in health and nutrition aspect, and then followed by other human aspects including economy and social. It is, therefore, eradicating TB in an effective and efficient way becomes a very emerging issue on TB treatment strategy. Since TB is an immune-related disease, hence, enhancing the immune system might be considered as an important strategy to be considered on TB treatment. Zinc, vitamin A and a new discovered protein, leptin, take a part on that issue. A cross sectional study was conducted with a main objective of investigating the relationship between nutritional and leptin status of new diagnosed pulmonary TB disease with the disease severity in selected districts of East Nusa Tenggara province, Indonesia. This research report is divided into three parts. Part 1 includes comprehensive reviews on the background of the study, literature review, problem statement and rationale, objective, hypotheses, conceptual framework and variable indicator matrix. Part 2 wraps up the manuscript for publication, entitled "Micronutrients and Leptin status Are Associated with the Radiological Features Among New Diagnosed Pulmonary Tuberculosis Patients." It is written and formatted based on author's guideline of the Journal of Nutrition. Part 3 covers the supporting documents including detailed methodology and other result, author's guideline of the journal, questionnaire, ethical approval, informed consent, official permit letter, references and curriculum vitae. It is expected that the results of this study may contribute to the body of knowledge about the severity of TB that reflects the specific profile of nutritional status (body fat, BMI, MUAC and micronutrient status) and plasma leptin. Furthermore, it will serve as reference data for further investigations, better interventions and treatments on active pulmonary TB patients."

"Salah satu mekanisme terjadinya resistensi leptin pada obesitas adalah kelainan reseptor leptin (Ob-R)."

"Salah satu mekanisme terjadinya resistemi leptin pada obesitas adalah kelainan reseptor leptin (Ob-R). Beberapa penelitian membuklikan bahwa aktifitas ikatan leptin di serum manusia berhubungan dengan reseptor leptin terlarut (soluble leptin receptor) dan restriksi asupan energi menyebabkan penurunan kadar leptin darah. Penelitian ini adalah untuk mengetahui beda kadar reseptor leptin terlarut serum dan densitas reseptor leptin dijaringan lemak adventitial aorta setelah dilakukan restriksi diet selama 4 minggu. Kadar reseptor leptin terlarut diukur dengan ELISA dan densitas reseptor leptin di jaringan lemak dengan irnunohistokimia. Kadar reseptor leptin terlarut pada kelompok perlakuan 40% diet normal lebih rendah dibanding kontrol (p=0,02). Tidak didapaikan perbedaan reseptor leptin terlarut yang bermakna antara kelompok perlakuan 40% diet normal, 1 hari puasa-1 hari makan normal dan 1 hari pitasa-2 hari makan normal. Di sisi lain, densitas reseplor leptin dijaringan lemak advenlitia aorta justru lebih tinggi pada kelompok restriksi 40% daripada kontrol. Restriksi diet 40% kalori normal harian menurunkan kadar reseptor leptin terlarut di serum, tetapi meningkatkan densitas reseptor leptin dijaringan lemak advential aorta tikus. Perubahan ini mungkin merupakan akibat mekanisme up regulation dalani mempertahankan homeostasis. (Med J Indones 2006; 15:145-50)

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One of the five possible mechanisms of leptin resistance in human obesity is the defect in the leptin receptor (Ob-R). Evidence has accumulated that leptin-binding activity in human serum is related to a soluble form of the leptin receptor, and restriction of energy intake resulted a decrease in circulating leptin levels. Aim of this study is to examine the difference of serum soluble leptin receptor level and ieplin receptor density in rat adipose tissue of adventitial aorta after four weeks treated with different restricted diets. Soluble leptin receptor level was measured by ELISA and leptin receptor density by using immuno-hisfochemistry. The soluble leptin receptor in group treated with 40% of normal daily calori diet was found significantly lower than control (p = 0.02). There were no any significant differences among group treated with 40 % of normal daily calori diet, "I day fast-] day eat", and "ldayfaxt-2 days eat" groups, and among I day fast-1 day eat", "day fast - 2 days eat" and control groups as well. On the other hand, leptin receptor density in adipose tissues was higher in restricted diet group than control. Diet of 40 % normal daily calorie for 4 weeks decreased soluble leptin receptor level, but increased adipocyte leptin receptor density of the adipose tissue of rat adventitial aorta. These changes may be resulted from an up regulation mechanism in relation with homeostatic maintenance. (Med J Indones 2006; 15:145-50)"

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 Leptin berfungsi untuk menjaga keseimbangan energi untuk mencegah penambahan berat badan dalam menurunkan risiko resistensi leptin. Peningkatan leptin dipengaruhi oleh jumlah simpanan lemak dan perubahan akut dari asupan makanan. Asupan energi mempengaruhi sekresi leptin untuk menjaga keseimbangan energi. Healthy eating index (HEI) tinggi diartikan kualitas diet yang baik mencegah penyimpanan lemak dan peningkatan berat badan. Kami bertujuan untuk mengetahui hubungan antara HEI dan asupan energi total dengan kadar leptin pada orang dewasa perkotaan Jakarta. Teknik pengambilan sampel adalah metode konsekutif dan diperoleh 110 subjek yang memenuhi kriteria penelitian. Pengambilan data melalui 3 kali 24 jam food recall, pengukuran antropometri dan pengambilan serum darah. Asupan energi total rata-rata 1894 ± 482 kkal. Hasil skor HEI 36,5 (31,7-41,2). Hasil kadar leptin 15,7 (7,6-26,1) ng/ml. Hubungan signifikan negatif antara asupan energi total dengan kadar leptin (β -0,8, p=0,008) sebelum disesuaikan dengan usia, jenis kelamin dan IMT. Hubungan antara HEI dengan kadar leptin tidak didapatkan hubungan yang signifikan.

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The function of leptin is to maintain energy balance to prevent weight gain and reduce the risk of leptin resistance. High leptin is influenced by the amount of fat stores and acute changes in food intake. Energy intake affects leptin secretion to maintain energy balance. A high healthy eating index (HEI) means a good quality diet prevents fat storage and weight gain. We aimed to determine the relationship between HEI and total energy intake with leptin levels in Jakarta urban adults. The sampling technique was the concecutive method and obtained 110 subjects who met the research criteria. Data were collected through 3 times 24 hours of food recall, anthropometric measurements and taking blood serum. Average total energy intake was 1894 ± 482 kcal. HEI score 36.5 (31.7-41.2). The results of leptin levels were 15.7 (7.6-26.1) ng/ml. There was a significant negative relationship between total energy intake and leptin levels (β -0.8, p=0.008) before adjusting for age, sex and BMI. There was no significant relationship between HEI and leptin levels."

"Obesitas telah menyerang dengan kekuatan penuh dan dampaknya adalah meningkatnya prevalensi di seluruh dunia seiring dengan meningkatnya angka kematian dan penyakit yang berhubungan dengan obesitas. Faktor genetik, hormonal dan lingkungan berinteraksi satu sama lain menyebabkan obesitas. Diet rendah kalori dan gaya hidup aktif secara fisik adalah cara utama untuk menangani obesitas. Penanganan tambahan adalah melalui intervensi farmakologis, menggunakan dua obat baru, yaitu cyclobutane methanamine HCl dan tetrahidrolipstatin, yang potensial untuk pengaturan obesitas. Cara terakhir untuk memecahkan masalah ini adalah dengan melakukan pembedahan. Akhir kata, pasien harus berkonsultasi dengan dokternya dalam memutuskan metode mana yang paling efektif untuk mencari solusi terhadap obesitas. (Med J Indones 2003; 12: 53-62)

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Obesity has struck with all its might and the results are the increased world-wide prevalence along with increased mortality rate and other obesity-related diseases. Genetic, hormonal and environmental factors interact to cause obesity. Very low calorie diet and physically active lifestyle are the primary means to treat obesity. Additional intervention is by pharmacological treatment, using two new drugs, namely cyclobutane methanamine HCl and tetra hidrolipstatin that are potential for the management of obesity. Another way to solve this problem is by performing a surgery. In conclusion, patients should consult their physicians in order to decide which methods are the most effective to find a solution to combat obesity. (Med J Indones 2003; 12: 53-62)"

"Pengaruh pemberian diet rendah kalori seimbang selama 14 hari terhadap berat badan (BB), indeks massa tubuh (IMT), tebal lipatan kulit total (TLK), massa lemak tubuh (ML), massa tubuh bebas lemak(MBL), rasio lingkar pinggang-lingkar panggul (RLpi-Lpa), dan kadar leptin serum, telah dievaluasi dengan studi eksperimental pra dan pasca pemberian diet rendah kalori seimbang 915,23 kkal dengan komposisi 55,81% karbohidrat, 19,46% protein dan 24,73% lemak selama 14 hari terhadap 39 subyek perempuan obes (19-55 tahun) yang telah memenuhi criteria penerimaan dan penolakan. Data yang dikumpulkan meliputi data karakteristik demografi, data asupan energi dan makronutrien, antropometri, komposisi tubuh, dan kadar leptin serum. Terjadi penurunan berat badan secara bermakna (p<0,05) dari 70,99 ± 8,62 menjadi 68,81 ± 8,36 kg (3,07%); penurunan IMT secara bermakna (p<0,05) dari 30,28 ± 3,11 kg/m2 menjadi 29,36 ± 2,94 kg/m2 (3,04%); penurunan TLK secara bermakna (p<0,05) dari 99,36 ± 12,07 mm menjadi 91,29 ± 10,85 mm (8,08%); penurunan ML secara bermakna (p<0,05) dari 35,41 ± 2,75 % menjadi 33,65 ± 2,73 % (1,76%); peningkatan MBL secara bermakna (p<0,05) dari 64,59 ± 2,74 menjadi 66,35 ± 2,73 (2,72%); penurunan Lpi secara bermakna (p<0,05) dari 85,87 ± 7,31 menjadi 83,35 ± 7,09 (2,93%); penurunan Lpa secara bermakna (p<0,05) dari 107,59 ± 6,67 menjadi 106,49 ± 6,37 (1,02%); penurunan Lpi-Lpa secara bermakna (p<0,05) dari 0,80 ± 0,05 menjadi 0,78 ± 0,04 (2,24%); penurunan kadar leptin secara bermakna (p<0,05) dari 23,31 (12,06-71,22) menjadi 18,18 (7,90-65,11) (22,01%); ditemukan korelasi positif antara kadar leptin serum dengan ML secara bermakna (p<0,05) sebelum perlakuan (r=0,47 ; p=0,003) dan sesudah perlakuan (r=0,57 ; p=0,001). Pemberian diet rendah kalori seimbang sebesar 915,23 kkal/h selama 14 hari dapat dengan efektif menurunkan berat badan, IMT, tebal lemak bawah kulit, persentase lemak, meningkatkan persentase massa bebas lemak, menurunkan rasio lingkar pinggang, lingkar panggul dan kadar leptin serum. (Med J Indones 2005; 14: 220-4)

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The effect of balanced low-calorie diet for 14 days on body weight (BW), body mass index (BMI), total skin fold thickness (SFT), fat mass (FM), fat free mass (FFM), waist to hip ratio (WHR) and serum leptin level was evaluated by using a pre and post-experimental balanced low-calorie diet 915.23 kcal/day with the composition of 55.81% carbohydrate, 19.46% protein and 24.73% fat for 14 days on 39 obese-women subjects (19-55 years old) who have met the inclusion and exclusion criteria. The collected data include demographic characteristic, macronutrient and energy intake, as well as of anthropometry, FM, FFM, and serum leptin level. Body weight reduction occurs significantly (p<0.05) from 70.99 ± 8.62 to 68.81 ± 8.36 kg (3.07%); BMI reduction is significant (p<0.05) from 30.28 ± 3.11 kg/m2 to 29.36 ± 2.94 kg/m2 (3.04%); Significantly reduced SFT (p<0.05) from 99.36 ± 12.07 mm to 91.29 ± 10.85 mm (8.08%); Significantly reduced FM (p<0.05) from 35.41 ± 2.75 % to 33.65 ± 2.73% (1.76%); Significantly increased FFM percentage (p<0.05) from 64.59 ± 2.74 to 66.35 ± 2.73 (2.72%); Significantly reduced WC (waist circumference) (p<0.05) from 85.87 ± 7.31 to 83.35 ± 7.09 (2.93%); Significantly reduced HC (hip circumference) (p<0.05) from 107.59 ± 6.67 to 106.49 ± 6.37 (1.02%); Significantly reduced WHR (p<0.05) from 0.80 ± 0.05 to 0.78 ± 0.04 (2.24%); Significantly reduced serum leptin (p<0.05) from 23.31 (12.06-71.22) to 18.18 (7.90-65.11) (22.01%); positive correlation is observed between serum leptin level and FM significantly (p<0.05) before treatment (r=0.47 ; p=0.003) and after treatment (r=0.57 ; p=0.001). Balanced low-calorie diet may effectively reduce body weight, BMI, skin fold thickness, percentage of fat mass, to increase percentage of fat free mass, to reduce waist to hip ratio and serum leptin level. (Med J Indones 2005; 14: 220-4)"

"Tujuan : Mengetahui pengaruh pemberian diet rendah kalori seimbang selama 14 hari terhadap berat badan (BB), indeks massa tubuh (IMT), tebal lipatan kulit total. (TLK), massa lemak tubuh (ML), massa tubuh bebas lemak (MBL), rasio lingkar pinggang-lingkar panggul (R Lpi-Lpa) , dan kadar leptin serum.Tempat : Rumah Sakit Sumba Waras, GrogolBahan dan cara: Penelitian ini merupakan studi eksperimentai pra dan pasca pemberian diet rendah kalori seimbang 915,23 kkal dengan komposisi 55,81% karbohidrat, 19,46% protein dan 24,73% lemak selama 14 hari terhadap 39 subyek perempuan obes (19-55 tahun) yang telah memenuhi kriteria penerimaan dan penolakan. Data yang dikumpulkan meliputi data karateristik demografi, data asupan energi dan makronutrien, antropornetri, komposisi tubuh, dan kadar leptin serum.Hasil : Terjadi penurunan berat badan secara bermakna (p<0,05) dari 70,99 ± 8,62 menjadi 68,81 ± 8,36 kg (3,07%); penurunan IMT secara bermakna (p<0,05) dari 30,20 ± 3,11 kg/m2 menjadi 29,36 ± 2,94 kg/m2 ( 3,04%); penurunan TLK secara bermakna (p<0,05) dari 99,32 ± 12,07 mm menjadi 91,29 f 10,85 mm (8,08%); penurunan ML secara bermakna (p<0,05) dari 35,41 ± 2,75 % menjadi 33,65 ± 2,73% (1,76 %) peningkatan persentase MBL secara bermakna. (p<0,O5) dari 64,59 2,74 menjadi 66,35 2,73% (2,72%);penurunan Lpi secara bermakna (p<0,O5) dari 85,87 7,31 menjadi 83,35 ± 7,09 cm (2,93%); penurunan Lpa secara bermakna (p<0,05) Bari 107,59 ± 6,67 menjadi 106,49 f 6,37 cm (1,02%); penurunan R Lpi-Lpa secara bermakna (p(O,O5) dari 0,80 ± 0,05 menjadi 0,78 ± 0,04 (2,24 %); penurunan kadar leptin serum secara bermalma (p<0,05) dari 23,31 (12,06-71,22) menjadi 18,18 (7,90-65,11) pg/mL (22,01 %); ditemukan korelasi positif antara kadar leptin serum dengan ML secara bermakna (p<0,05) sebelum perlakuan 0=0,47 ; p t,003) dan sesudah perlakuan (r3,57 ; p=0,001).Simpulan : Pemberian diet rendah kalori seimbang sebesar 915,23 kkal/h selama 14 hari dapat dengan efektif menurunkan berat badan, IMT, tebal lemak bawah kulit, persentase lemak, meningkatkan persentase massa bebas lemak, menurunkan rasio lingkar pinggang lingkar panggul dan kadar leptin serum, serta ditemukan korelasi positif bermakna antara massa lemak tubuh dan leptin serum baik sebelum maupun sesudah perlakuan.

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Objective : To identify the effect of balanced low-calorie diet for 14 days on body weight (BW), body mass index (BMI), total skin fold thickness (SFT), fat mass (FM), fat-free mass (FFM), waist to hip ratio (WHR) and serum leptin level.

Place : Sumber Waras Hospital, Grogol

Material and Method : This study is a pre- and post-experimental balanced low-calorie diet 915.23 kcallday with the composition of 55.81 % carbohydrate, 19.46 % protein and 24.73 % fat for 14 days on 39 obese-women subjects (19-55 years old) who have met the inclusion and exclusion criteria. The collected data include demographic characteristic, macronutrient and energy intake, as well as of anthropometry, FM, FFM, and serum leptin level.

Results : Body weight reduction occurs significantly (p<0.05) from 70.99 ± 8.62 to 68.81 ± 8.36 kg (3,07%), BMI reduction is significant (p<0.45) from 30,20 + 3,11kglm2 to 29,36 ± 2,94 kghn' (3,04%); significantly reduced SFT (p<0.05) from 99,32 ± 12,07 mm to 91,29 ± 10,85 mm (8,08%); significantly reduced FM (p<0,05) from 35.41 ± 2.75% to 33.65 ± 2.73% (1.76%); significantly increased FFM percentage (P<0.05) from 64.59 ± 2.74 to 66.35 ± 2.73 (2.72%); significantly reduced WC (waist circumference) (p<0.05) from 85.87 ± 7.31 to 83.35 ± 7.09 (2.93%); significantly reduced HC (hip circumference) (p<0.05) from 107.59 ± 6.67 to 106.49 ± 6.37 (1.02%); significantly reduced WHR (p<0.05) from 0.80 ± 0.05 to 0.78 ± 0.04 (2.24%); significantly reduced serum leptin level (p<0.05) from 23.31 (12.06 - 71.22) to 18.18 (7.90 - 65.11) (22.01%); positive correlation is observed between serum leptin level and FM significantly (p<0,05) before treatment (r= 0.47; p = 0.003) and after treatment (r=0,57;

Conclusions : Balanced low-calorie diet may effectively reduce body weight, BMI, skin fold thickness, percentage of fat mass, to increase percentage of fat free mass, to reduce waist to hip ratio and serum leptin level. There is a statistically significant positive correlation between serum leptin and body fat mass both before and after treatment."

"ABSTRAKLatar Belakang: Leptin yang diketemukan oleh Zhang dan Friedman pada tahun 1994, dihasilkan oleh adiposit dan berhubungan dengan obesitas. Pada hewan coba, selain mempengaruhi homeostasis berat badan, leptin juga mempengaruhi metabolisme lipid pada jaringan perifer, seperti lipolisis dan lipogenesis. Peningkatan lipolisis dan penurunan lipogenesis menyebabkan peningkatan asam lemak bebas, yang kemudian diikuti oleh peningkatan konsentrasi trigliserida. Pada saat konsentrasi trigliserida tinggi, terjadi pembentukan small dense LDL, yang merupakan komponen dari dislipidemia aterogenik, terutama pada individu obes. Penelitian ini berusaha memperlihatkan perbedaan antara konsentrasi leptin dan profil lipid pada obes dan non-obes, dan terdapatnya hubungan antara leptin dan small dense LDL pada obesitas.Subyek: Berhasil dikumpulkan 297 laki-laki subyek penelitian, yang terdiri dari 205 subyek dengan obesitas sentral dan 92 subyek non-obes, yang presentase terbesar berusia antara 30-59 tahun. Variabel yang diamati pada penelitan ini antara lain, Indeks Massa Tubuh (IMT), lingkar perut, konsentrasi leptin, trigliserida, asam lemak bebas, kolesterol LDL, ApoB, ratio kolesterol LDL dan ApoB, kolesterol HDL, glukosa puasa dan insulin.Metodologi: Penelitian ini menggunakan disain potong lintang, Hubungan antara leptin dengan variabel-variabel seperti IMT, lingkar perut, leptin, trigliserida asam lemak bebas, kolesterol LDL, ApoB, kolesterol HDL dan insulin dianalisis dengan unpaired Nest, dibandingkan antara kelompok obes sentral dan non-obes. Sedangkan hubungan antara leptin dan small dense LDL dianalisis dengan menggunakan regresi logistik.Pemeriksaan laboratorium dari tiap variabel dilakukan dengan metode antara lain, konsentrasi trigliserida dan asam lemak bebas diukur dengan metode kolorimetri enzimatik, kolesterol LDL dan kolesterol HDL diukur dengan metode homogenisasi. Konsentrasi insulin diukur dengan metode ELISA, kadar leptin diukur dengan metode immunoassay.Hasil dan Pembahasan: Terdapat perbedaan karateristik antara kelompok obes dan non-obes, antara lain plasma leptin lebih tinggi pada kelompok obes sentral dibandingkan dengan kelompok normal; 9,71 (1,92) ng/mL vs. 2,63 (2,09) ng/mL, (P<0,001); rerata trigliserida 159,1 (6,97) mg/dL vs. 119,4 (4,8) mg/dL; (P<0,001), asam lemak bebas 0,42 (0,01) mmol/L vs. 0,36 (0,02) mmol/L; (p=0,001), apoB 108,05 (21,1) mg/dL vs. 101,4 (20,4) mg/dL(p=0,012) juga lebih tinggi pada kelompok obes dibandingkan non-obes, kolesterol HDL lebih rendah pada kelompok obes yaitu 40,6 (1,2) mg/dL vs. 46,2 (1,2) mg/dL; (P<0,001). Sedangkan rerata kolesterol LDL tidak berbeda bermakna antara kelompok obes dan non-obes 138,9 (32,2) mg/dL vs. 137,8 (31,9) mg/dL; (P=0,792). Pada subyek dengan Inleptin < 7,5 pg/mL (1,8 ng/mL) peningkatan kemungkinan didapatkannya small dense LDL sebesar 5,92 kali dibandingkan dengan subyek dengan lnleptin > 9,87 pg/mL (19,34 ng/mL).Penentuan indeks massa tubuh sebagai kriteria obesitas; penelitian ini memperkuat pendapat untuk menggunakan kriteria Asia Pasifik (1MT > 25 kg/m2) sebagai klasifikasi indeks massa tubuh (IMT) untuk populasi orang Indonesia.Hubungan lingkar perut dengan small dense LDL, leptin, IMT, dan HOMA-IR; Lingkar perut mempunyai korelasi yang baik dan bermakna secara statistik dengan konsentrasi leptin (r=0,72 dan P<0,05) dan HOMA-IR (r~0,53 dan P<0,05). Lingkar perut pada subyek dengan dan tanpa small dense LDL berbeda bermakna (P=0,016).Nilai normal konsentrasi leptin bagi IMT normal adalah 2,04 ng/mL dengan kisaran: 0,45 - 9,26 ng/mL. dan rerata konsentrasi leptin pada subyek obes sentral adalah 9,71 ng/mL dan subyek non-obes : 2,63 ng/mL.Resistensi dan defisiensi leptin pada obesitas; pada obesitas sentral dapat terjadi resistensi leptin atau defisiensi leptin dan mungkin ambang terjadinya resistensi leptin pada subyek penelitian ini lebih rendah (< 20 ng/mL) dibandingkan etnik Kaukasia.Peran enzim lipase hepatik (HL) pada pembentukan small dense LDL; hubungan peningkatan konsentrasi leptin dengan didapatkannya small dense LDL dapat dihubungkan dengan efek enzim lipase hepatik. Bila pengaruh leptin terhadap didapatkannya small dense LDL terjadi dengan bantuan enzim lipase hepatik (HL) sebagai katalisator dapat dibuktikan, maka akan memperkuat bukti adanya hubungan antara leptin dengan didapatkannya small dense LDL.Hipotesis baru penelitian ini adalah, leptin mempunyai efek inhibisi terhadap enzim lipase hepatik di hati, atau analog dengan efek inhibisi insulin terhadap enzim HSL pada adiposit.Hasil penelitian dibandingkan dengan penelitian lipid sebelumnya; hasil penelitian ini dapat membuktikan perbedaan leptin dan profil lipid, yaitu konsentrasi asam lemak bebas, trigliserida dan kolesterol HDL pada kelompok subyek obesitas sentral dan subyek non-obes. Beberapa penelitian sebelumnya memberikan hasil yang berbeda.Simpulan: Penelitian ini adalah penelitian pertama yang membandingkan konsentrasi leptin dan hubungannya dengan small dense LDL pada kelompok obes dan non-obes pada populasi di Indonesia maupun di dunia. Hasil penelitian ini memperlihatkan bahwa konsentrasi leptin lebih tinggi secara bermakna pada kelompok obes sentral dibandingkan dengan kelompok non-obes, serta berhubungan secara bermakna dengan konsentrasi trigliserida, asam lemak bebas, apoB dan kolesterol HOL. Lebih jauh lagi, penelitian ini juga memperlihatkan hubungan antara leptin dan didapatkannya small dense LDL, di mana makin rendah leptin akan makin meningkatkan kemungkinan terdapatnya small dense LDL, Pada laki-laki dengan obesitas sentral, leptin berhubungan dengan prediksi didapatkannya small dense LDL. Leptin secara independen mempunyai efek protektif terhadap didapatkannya small dense LDL.

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ABSTRACT

Background: Leptin which is discovered by Zhang and Friedman (1994) is secreted by adipocytes and associated with obesity. In animals it has been shown that beside its effect on weight homeostasis, leptin also exerts peripheral effects that include lipid metabolism, i.e. lipogenesis and lipolysis. The results of studies on humans are conflicting. The increased lipolysis and decreased lipogenesis resulted in an increase synthesis of fatty acids which is followed by triglycerides. At a certain level of triglycerides, small dense LDL formation occur, an established component of atherogenic lipoprotein phenotype (ALP). Leptin has been implicated in this process especially in central obese individuals. The aim of the study is to show that leptin and lipid levels are higher in central obese as compared to non-obese individuals and to investigate the relationship between leptin levels and small dense LDL in central obese individuals.

Subjects: A total of 297 male subjects comprising 205 central obese and 92 nonobese age 30-59 years were enrolled in the study. Variables under study includes body mass index (BMI), serum leptin, triglyceride, free fatty acids, LDL-cholesterol, apoB, LDL-cholesterollapoB ratio, HDL-cholesterol and insulin levels.

Methods: This is a cross sectional study. The correlation between leptin and some variables, such as body mass index (BMI), triglycerides, free fatty acids, LDL-cholesterol, apoB, LDL-cholesterollapoB ratio, HDL-cholesterol and insulin levels was analyzed by unpaired t-test. Correlation between leptin and small dense LDL was analyzed by logistic regression. Plasma tryglycerides and free fatty acids were measured by enzymatic colorimetry method; apoB by immunoturbidimetry, LDL-cholesterol and HDL-cholesterol by homogenous method, insulin level by enzym-linked immunosorbent assay (BLISA), Plasma leptin was measured by immunoassay.

Results & Discussion: The characteristics between obese and nonobese subjects were different, such as mean plasma leptin levels were significantly higher in central obese than in nonobese individuals 9.71 (1.92) ng/mL vs. 2.63 (2.09) ng/mL, (P<0.001); mean triglycerides 159.1 (6.97) mg/dL vs. 119.4 (4.8) mg/dL; (P<0.001), free fatty acids 0.42 (0.01) mmol/L vs. 0.36 (0.02) mmol/L; (P=0.001), apoB 108.05 (21.1) mg/dL vs. 101.4 (20.4) mg/dL (P=0.012) were also higher in central obese than in nonobese individuals, and HDL-cholesterol is lower 40.6 (1.2) mg/dL vs. 46.2 (1.2) mg/dL; (P<0.001). LDL-cholesterol 138.9 (32.2) mg/dL vs. 137.8 (31.9) mg/dL (P=0.792). Among subjects with lnleptin < 7.5 pg/mL (L8 ng/mL) the risk of having small dense LDL increases by 5.92 times compared to subjects with lnleptin 9.87 pg/mL (19.34 ng/mL).

In regard to body mass index and the classification of obesity, the present study is in favor with the Asia Pacific classification and criteria for obesity, i.e. BMI > 25 kg/rn2 to be used for Indonesian population.

Relationship between waist circumferences, small dense LDL, leptin, BMI, dan HOMA-IR. There is a statistically significant strong relationship between waist circumference and leptin (r=0.72; P<0.05) and HOMA-IR P<0.05). Furthermore, mean of waist circumference differ significantly between subjects with and without small dense LDL (P=0.016).

Normal leptin levels for subjects with normal BMI is 2.04 ng/mL (range 0.45-9.26 ng/mL); and mean leptin levels for obese and nonobese were 9.71 and 2.63 ng/mL, respectively.

In regard to leptin resistance and leptin deficiency in obese subjects. Both leptin resistance and leptin dificiency is found in obese subjects, and the result indicate that leptin resistance in this population developed at lower leptin level (<20 ng/mL) as compared to Caucasian.

The possible role of hepatic lipase in small dense LDL formation. The relationship of increased leptin levels and the presence of small dense LDL could possibly be due to hepatic lipase (HL) effect. If the effect of leptin on small dense LDL formation is by way of HL as catalysator can be proven, this finding will then support the evidence of relationship between leptin and small dense LDL.

The hypothesis generated from the present study is that leptin inhibits the effect of HL in the liver in analogy with the inhibitory effect of insulin on HSL in the adipocyte.

Results arising from the present study support the view that leptin levels and lipid profile, i.e. free fatty acids, triglycerides, dan HDL cholesterol in obese differ from nonobese subjects, whereas other studies give different results.

Conclusion: This is the first study that compare leptin levels and determine the relationship between leptin and small dense LDL in central obese and nonobese male Indonesian subjects. The results showed that leptin levels are significantly higher in central obese as compared to nonobese individuals, and is correlated with triglycerides, free fatty acids, apoB and HDL-cholesterol in central obese individuals. Furthermore, this study also showed a relationship between leptin levels and small dense LDL in central obese individuals, in which lower leptin levels carries a higher probability of having more small dense LDL. Leptin has an independent protective effect for the occurrence of small dense LDL."

"A study on the effect of solvent extract of pomegranate pericarpium towards the appitite,body weight and leptin serum level of 15 male albino rats had been carried out....."