IBN AL- HAITHAM J. FO R PURE & APPL. SC I. VO L.24 (3) 2011 Serumleptin, Triglycerides, Cholestrol and Hdl- Cholestrol In Non Dlabetic Obese Subjects M.A. Kassim Departme nt of Biology, College of Science ،Unive rsity of Al-Mustansyria Received in : 16 February 2011 Accepte d in: 16 June 2011 Abstract T his st udy was carried out t o investigat e t he relat ion ship between Serum lept in, Body Mass Index (BMI), T riglycerides, Cho lestero l and HDL- Cholestero l in Non Diabet ic Obese subject s comp aring with healt hy subject . A 36 male an d female Iraqis obese were st udied, mean age 50.1, 43.3 years respectively and 23 healt hy subject s. Serum lept in, T riglycerides, Cho lestero l and HDL- Cholestero l were measured. Lep t in, T riglycerides, Cho lestero l, HDL- Cho lestero l and BMI significan t ly increased in obese males and fem ales comp ared wit h cont ro l, but t here was no significan t difference in HDL- Cholestero l and BMI when comp ared bet ween obese males and fem ales. A low significan t po sitive correlat ion was fo und between lept in and HDL- Cholestero l, and no significant difference bet ween lept in and ot her t ypes of lipids. T he findings suggested that serum lept in concent rat ion t op mo st in obese subject s wit h not iceable effect on lipid met abolism. Key word: Serum lept in, Obesity, lip ids Introduction Obesity is in creasing progressively wor ldwi de, It is closely associat ed wit h increased morbidit y an d mo rt ality caused by several of t he most common diseases in t he wor ld including gallst one diseases and cancer [1]. Obesit y is det ermin ed by an int eraction between environmental, psychosocial, and genet ic factors [2 ]. Lept in (from the Greek wor d leptose, meanin g thin) is a protein hormone that is encoded by t he Ob gene and is secreted by adipose t issue t o in t he circulat ion. It act s mainly in t he h ypothalamus by binding to specific Lept in recepto r and regulat es fo od intake and energy balance [3 ]. In addit ion Lept in act ivat es sympathetic nervous syst em and increases energy expendit ure. Lept in t hus decreases body weight and adiposity as a novel messenger of energy met abolism [4]. The informat ion concerning t he relationship between serum Lept in concentrat ion and levels of serum lipids is important . Furt hermore, when evaluat ing Leptin levels and met abolic prof iles of patients with and wit ho ut ischemic heart disease, no differences in Lept in concent rat ion and no relat ion ships between Lept in and plasma lipid were observed [5]. However, serum Leptin concentrat ion in individuals wit h first- ever hemo rrh agic st roke was sharply higher t han in cont ro ls suggesting some associat ion between serum Lept in an d alt eration of lipid met abolism [6]. Therefore, the aim of t he present study is t o evaluat e serum Lept in, triglycerides, cholest erol and HDL- cholest erol in Iraqis obese people comparing with normal subject s. IBN AL- HAITHAM J . FO R PURE & APPL. SC I. VO L.24 (3) 2011 Materials and Methods Subjects A t ot al of 36 (1 6 male an d 20 fem ale) Iraqis obese (BMI ≥ 30 Kg / m 2 ) were enro lled in t his study. Median age of t he 3 6 fem ale/male v olunt eers was 43.0, 50 .1 years respect ively, ranged (20 -6 1) ,(20 - 78)y ears respect ively. T hese out-pat ient s were t urned up t o AL-Numan Hospit al laborat ory for check-up fo r t he p erio d fro m June t o August 2010 .A t ot al of 23 co nt ro l subject s(11 male and 12 female) with (BMI ≤ 25 Kg / m 2 ) were also en ro lled in t his study. Bot h t est an d con t ro l groups were non diabet ic (serum glucose concent rat ion ≤11 0) and wit h nor mal bloo d pr essure. BMI was calculated as weight (in kg) divided by squared height (in m 2 ). Sample Collections Fiv e milliliters (5m l) venous bloo d was obtained between 08:0 0 an d 10.00 a.m. aft er a 12 hour fasting perio d. All blood samples were dispensed int o dry glass t est t ubes fo r clot t ing and ret ract ion to take place. Sera were obtained aft er samples were cent rifuged at 200 0g for five min ut es and st ored at -20 °C unt il assayed fo r laborat or y investigat ion s [7]. Laboratory techniques Fasting serum glucose concent rat ion s had been measured by t he glucose oxidase pro cedure and serum HDL-cholestero l, t riglycerides, ch olestero l were measured enzymet ically by quant it at ive determination kit (SP INREACT , S.A.U. SP AIN). St or ed frozen sera samples were ret riev ed, t hawed, and t ested for Leptin levels by means of a quant it at ive en zyme immuno assay using a comm ercial kit (DRG Inst ruments GmbH, Germ any) (specificit y, 1 00%). Reference st andards were used to pro duce a st andard curve t o quant itate Lep t in levels. T he result s were ex pr essed in ng/ml. T he normal value for Lep t in levels was up 3.84±1.79 ng/ml in male an d 7.36±3 .73 ng/ml in fem ale. Statistical analysis T he st at istical co mp ut er soft ware package MINIT AB was used to an alyze t he data. The mean, range, and 95% confidence int erv al (C.I.) fo r median, were calculat ed. T he relat ion ships bet ween t he individual paramet ers were evaluated using Spearm an’s correlat ion . P -v alue < 0.05 was considered stat istically significant . Results and Discussion The st udy included 36 obese and 23 control subject s were divided in t wo gro ups, males and females. Mean , range and 95 % confidence int erv al (CI) for age, serum Lept in, HDL, T riglyceride, Cholest erol, Gl ucose and BMI of obese fem ales and control females are shown in table (1 ). The mean ages of the obese females and co ntrol females were 43.3 years (20-61) and 30 years (21-28), respectively. All of the paramet ers in table (1 ) were significan t ly higher than t hose of t he control except glucose. Conversely, HDL and BMI were significant ly lower between obese females and cont rol females. T he same parameters were applied t o obese males and contro l males shown in t able (2 ), the mean ages of obese males 50.1 years (20-78) and 35.25 years (24-43), respect ively. Each of the param eters in t able (2) was significant ly high except glucose. In t able (3) the t riglyceride and ch olest erol showed high significan t increase in obese fem ales compared wit h males, while serum lept in showed low significan t. Conversely, HDL, glucose, BMI, and age sho wed non significant change bet ween obese males and obese females. The relationships bet ween t he st udied paramet ers in the o bese males and females group are sho wn in t able (4) . As expect ed a highly significant posit ive correlation was fo und bet ween BMI and serum leptin. In addit ion the t able demonst rat ed a low significant posit ive correlation between leptin and HDL. Furt hermore no significant correlat ion bet ween leptin an d cho lest erol, IBN AL- HAITHAM J. FO R PURE & APPL. SC I. VO L.24 (3 ) 2011 t riglyceride was fo un . Also t here was no significant correlation bet ween BMI and cholest ero l, t riglyceride, HDL. In humans, it is well established t hat plasma leptin levels are directly proport ional to percentage body fat . Most obese individuals have h igh co ncentrat ions of leptin in their serum and plasma but ex hibit leptin resistance because of decrease leptin transport into t he central nervous system or down regulat ion of leptin receptors [8, 9]. In our study higher leptin con centrat ion s were fo und in Iraqis obese males and fem ales (BMI ≥ 25.00kg/m 2 ) than the normal cont rol gro up. The difference bet ween the median of leptin in both obese males and fem ales was significan t depending on the distribut ion and composition of fat in t he body or depending on t he effect of sex st ero ids like est rogen and progesterone. [10, 11, 12] In t he subject s investigat ed in the present st udy, t he relation ship bet ween leptin and BMI was linear, as shown in t able 4. The results similarly results presented in this study in good agreement wit h result rep ort ed in Saudian ov erweight and obese fem ales in Makkah communit y [13 ], where significant relat ionship was fo und bet ween leptin, BMI and waist circumferen ce. Also t he result s seemed to agree wit h tho se reported by Chaisiri et al. in Japanese obese wom en [14], where a linear relationship between serum leptin and BMI was fo und. On t he other hand, t he relation ship bet ween lept in and BMI in Caucasian individuals is not linear in very obese person s because Caucasians have different metabolic stat es from Asians, in addit ion for t he differences might be the greater height of Caucasians, so t hat an increase in the v olume of fat t issue to a given height does not correspond in the same way as in Asians. The increase in fat t issue in Asians, wit h a relat ively short er height , results in a mor e direct relation ship between fat t issue an d BMI. It was fo und that blood-brain barrier t ransport at ion had a t hreshold level for serum leptin (about 25-30 ng/ml), above which increases in serum levels were not t ran slat ed into proport ional increases in cerebrospinal or brain leptin levels, which means t hat it may result in apparent leptin resistance and obesity[8]. Most inv est igat ions have demonst rated, in agreement wit h the dat a of t his study, a lack of correlat ion bet ween serum leptin and lipid prof iles [15,16,17,18,19] mainly when body weight and degree of adiposity are t aken int o acco unt Re ferences 1.Mantzoros,C.S . ،)1999 ( The role of leptin in human obesity and disease. A review of current evidence. Ann Int ern. Med, 130:651-657 2.Kopelman, P .G. . ،)20 00 ( Obesit y as a medical p ro blem. Nat ure,404:63 5-6 43 . 3.Ahima, R.S. and Flier, J.S .،)2000 ( Lep t in. Ann. Rev. P hy s.62 :41 3- 43 7. 4. Sagawa N., Yura S., It oh H., MIse H., Kakui K. Korit a D ) .200 2 ( Role of lept in in pregnancy- A rev iew. P lacent a:16 :S80- 86. 5. Sodenberg, S.; Ahr en, B.; Jansson, J.H ) .19 99 ( Lep t in is associat ed wit h increased risk o f my ocardial infract ion . J Int . Med.246:40 9- 418. 6.Couillard, C.; Mauriege, p.an d P rud hom mer, D. ) .19 97 ( P lasma lept in concent rat ion : gender differences and associat ion wit h met abolic risk fact ors for cardiov ascular disease. Diabet ologia ؛ 40:11 78 -1 18 4. 7. Alan, H.B. ) .20 06 ( T iet z Clinical Guide to Laborat ory T est ،4 th ed WB Saunders, P hiladelphia. 8.Caro , J.F.; Kolaczynski, J.W .an d Nyce, M.R. ).19 96 ( Decreased cerebrospinal fluid serum lept in ration in obesit y: A possible mechanism for lept in resistance .Lan cet ,348 :15 9- 161. 9.Bjorbaek, C.; El Haschimi, K.; Frant z, J.D.an d Flier, J.S. ) .19 99 ( T he role of SOCS -3 in lept in signaling and lept in resistance. J Biol. Chem.274 :30 059 -3 00 65 . IBN AL- HAITHAM J. FO R PURE & APPL. SC I. VO L.24 (3 ) 2011 10.Fluda, S.; Linseies, J.; Wolfram , G.; Him merch , S.; Gedrich; K., P ollmacher. T .an d Himmerich, H. . )20 10 ( Lep t in plasma levels in t he general pop ulat ion influence o f age, gender, body weight and medical histor y. P ro t ein P ept . Let t .17(1 1) :14 36 -1 44 0. 11.Min occin, A.; Savia, G.; Lucant on i, R.; Berselli, M.E.; T agliaferri, M.and Calo, G.an d P et ro ni, M.L. ).2000 ( Lep t in plasma concent rat ion are depend on body fat dist ribut ion in obese patients. Int. J. Obese Relat . Met ab. Disord24 . (9) : 113 9 - 1144 12.St even, M.; Heikki, M.; P auli, K.; Leena, M.and Markku, L. ).19 97 ( Lep t in concent rat ion sex hor mo nes, an d co rt isol in non diabet ic man. J. Clin. Endocrin ol and Met ab .82( 6):1807- 1813 . 13.Bahat hiq, A.O. ).201 0 ( relat ion ship of lept in hor mo nes wit h Body Mass In dex an d waist circumference in Saudi female p opulat ion of t he Makkah co mm unit y. T he Open Obesity J.2:95 -1 00. 14.Chaisiri, K.; P ongpaew, P .; T ungtron gchit r, R.; P hon rat , B.; Kullrap , S. and Schelp, F.P ) .19 98 ( Nutr it ion al st at us an d serum lipids of a rural p op ulat ion in Nort heast T hailandan ex ample of healt h t ran sition . In t . J. Vit am. Nutr. Res.68:19 6-2 02. 15.De court en, M.; Zimm et , P .an d Hodge, A. ) .199 7 ( Hyperlept inaemia: T he missing link in the metabolic syndrome? Diabet. Med.14 :20 0- 208. 16.Haluzik, M.; Fiedler, J.and Nedvidkova, J. ) .20 00 ( Serum lept in levels in pat ient s wit h hyp erlip idemias. Nutrit ion . 16 :42 9-4 33. 17.Leyva, F.; Godsland, I.F.and Ghat ei, M. ) .19 98 ( Hyperlep t inemia as acomp onent of met abolic syndrome o f cardiov ascular risk. Art erio scler T hro mb Vasc. Biol.18:92 8-9 33. 18.Ryan,A.S.an d Nicklas, B.J. ) .19 99 ( Age-relat ed changes in fat deposition in mid-t high muscle in wom en: relat ion ships wit h met abolic cardiovascular disease risk fact ors. In t . J. Obes126- 23 :-132. 19. Ho, S.C. ;T ai, E.S.an d Eng, P .H.K. (1 999 ) A st udy in t he relat ion ship between lept in, insulin and body fat in Asian subject . I nt . J. Obes.; 23: 246 -2 52 . Tabl e : )1 ( Mean, ranges an d 95% C I of age , le pti n, H DL, Tri gly ceri de , Ch oleste rol, Glu cose and BMI in obese and cont rol females Control Fem ale O bese Fem ale Norm al value P- value 95 %C I Mean (range ) 95 %C I Mean (range) Parame ters 0.00 21.6-23.8 30 (21-28) 33.5-41.81 43.3(20-61) Age yrs 20-25 0.05 22.3-23.1 24.3(21.5-25.3) 26.3-30.8 31.27(30-34.6) BMI Kg/m 2 7.3 0.00 0.4-1.2 2.8(1.8-7) 8.3-11.6 15.83(1.2-50.7) Lept in mg/ml 40-140 0.00 82.4-110.9 106.1(79.6-132.7) 141.2-156.8 172.78(70.7-265) Triglyce ride mg/dl 250-140 0.00 115.7-130.8 138.8(108-154.5) 196.3-218.2 198.47(69.5-243) Cholest ero l mg/dl 72-40 0.01 46.3-526 57.9(54-61.7) 41.3-48.6 46.49(38.6-61.7) HDL mg/dl 70-110 N.S. 75.6-81.7 79.2(72-84.6) 75.4-88.6 83.35(55.8-110) Gl ucose mg/dl BMI = body mass index, HDL-C= high density lipoprotein cho lest erol, Significant difference bet ween obese Female and cont ro l Female subject s p ≥0.05 IBN AL- HAITHAM J. FO R PURE & APPL. SC I. VO L.24 (3 ) 2011 Tabl e (2): Me an, ranges an d 95%C I of age, leptin , HDL, Triglyce ri de, Choles terol, Glucose an d B MI in obese an d control males Control male Male Obese Norm al value P-val ue 95 % C I Mean (range ) 95 % C I Mean (range( Paramet e rs 0.01 39- 6 .28 .1 35-25(24-43) 6 .51- 6 .33 )78 -20 (1 .50 Age yrs 25-20 0.05 1 .23- 1 .21 )25.3- 5 . 21( 24 1 .32 -6 .29 )1 .38 -30 (7 .32 BMI Kg/m 2 3.8 0.00 1.1 -37 .0 1.7(1-4) 6 .10- 9 .6 )1 .44 -3 .1 (4. 17 Lept in mg/ml 160-60 0.00 198- 3 .95 )106 - 106 (106 1 .163 – 6 .128 136.(70.7-273) Triglycer ide mg/dl 140-250 0.00 118.3- 78 .91 )131 - 9 .84( 108 6 .191 – 3 .146 169.5(96.5-243.2) Choleste ro l mg/dl 40-72 0.00 54.81-59.1 )7 .61 -65 (35 .63 7 .51 – 13 .43 49.9(34.7-65.6) HDL mg/dl 70-110 N.S. 68.6-81.33 82.8(75.6-90) 63 .88 – 3 .85 93.9(72-113.6) Gl ucose mg/dl BMI = body mass index, HDL-C= high densit y lipoprotein cholest ero l, Significant difference bet ween obese male an d cont rol male subject s p ≤ 0.05 Tabl e (3) Me an , ranges an d 95%C I of age, le ptin , HDL, Tri glyceri de , Choleste rol , Gl ucose an d BMI in O bese males and fem ales Obese fem ale Obese male P-val ue 95 %C I Mean (range( 95 %C I Mean (range( Paramete rs N.S. 33.5-41.81 43.3(20-61) 33.6-51.6 50.1(20-78) Age yrs N.S. 26.3-30.8 31.27(30.65) 29.6-32.1 32.7(30-38.1) BMI Kg/m 2 0.05 8.3-11.6 15.83(1.2-50.7) 6.9-10.6 17.4(1.3-44.1) Lept in mg/ml 0.001 156.8 -141.2 . 172.78(70.7-265) 128.6-163.1 136.9(70.7-274) Triglyceride mg/dl 0.00 2218. -3 .196 198.47(89.5-243) 146.3-191.6 169.5(96.5-243.3) Cholesterol mg/dl N.S. 41.3-48.6 46.49(38.6-16.7) 43.13-51.7 49.9(34.7-65.6) HDL mg/dl N.S. 75.4-88.6 83.35(55.8-110) 85.3-88.63 93.9(72-113.5) Gl ucose mg/dl BMI = body mass index, HDL-C= high densit y lipoprotein cholest ero l, Significant difference between obese male and cont ro l female subject s p ≤ 0.05 Tabl e (4) C orrel ation coefficients of age , le ptin , HDL, Tri gl yce ri de , Chole ste rol an d BMI in o bese m ales an d female s Age BMI HDL Tri gly ce ri de Ch oleste ro l Leptin Paramete rs 0.361** 0.710** 0.205* -0.059 -0.029 1.00 Lept in 0.338** -0.043 0.204** 0.285** 1.00 -0.029 Cholesterol 0.201** - 0.041 -0.410** 1.00 0.285** -0.059 Triglyceride 0.244** -0.038 1.00 0.140** 0.204** 0.205* HDL 0.722 1.00 -0.038 0.041 -0.043 0.710** BMI 1.00 0.722 0.244** -0.201** 0.338** -0.361** Age Significant difference: *p <0.05,**p<0.01 رفة والتطبیقیة المجلد 2011) 3( 24مجلة ابن الهیثم للعلوم الص نیه عالیة الكثافة الكولسترول و البروتینات الده، الدهون الثالثیة ، هرمون اللبتین في مصل دم البدناء غیر المصابین بالسكر مهند عبد اإلله قاسم الجامعة ألمستنصریه،كلیة العلوم ، قسم علوم الحیاة 2011شباط 16:استلم البحث في 2011 حزیران 16: قبل البحث في الخالصة الكولسـترول فضــآل ، الـدهون الثالثیــة ، ) BMI(مؤشــر كتلـة الجســم ، رمــون اللبتـین تـم التحـري فــي هـذه الدراســة عـن العالقــة بـین ه شخصـآ مـن البـدناء 36شـملت الدراسـة . عن البروتینات الدهنیة عالیـة الكثافـة لـدى البـدناء غیـر المصـابین بمـرض السـكر مقارنـة باألصـحاء قـیس تركیـز هرمـون اللبتـین و نسـبة الـدهون . عینـة لألصـحاء 23لي و سـنة علـى التـوا 43,3: 50,1العراقیین ذكورا و إناثا لهم معـدل عمـر ، لــوحظ وجــود فـرق معنــوي وزیــادة بتركیــز هرمــون اللبتــین ، و الــدهون الثالثیــة، و البروتینــات الدهنیـه عالیــة الكثافــة ،وشـملت الكولســترول عنـد عینـات الدراســة للبـدناء الـذكور و اإلنـاث مقارنــة BMIو الكولسـترول، و الـدهون الثالثیـة فضــآل عـن،البروتینـات الدهنیـه عالیـة الكثافــة عنـد المقارنـة بـین البــدناء الـذكور مـع البـدناء مــن BMIلكـن لـم یالحـظ وجــود فـرق معنـوي للبروتینـات الدهنیـة عالیــة الكثافـة، و ، باألصـحاء ات الدهنیـه عالیـة الكثافـة بینمـا لـم یالحـظ فـرق معنـوي كما وجد فرق معنـوي ایجـابي قلیـل فـي العالقـة بـین هرمـون اللبتـین و البروتینـ. اإلناث من تلك النتائج وجد أن هرمون اللبتین كان بمستوى عال عند األشخاص البدناء مقارنة باألصـحاء . بین هرمون البتین و بقیة أنواع الدهون .ولم یكن له تأثیر ملحوظ في التكوین األیضي للدهون مفتاحیة لكلمات ال الدھون , البدانة , ھرمون اللبتین : ا Age