Circulating Lp-PLA2 activity correlates with oxidative stress and cytokines in overweight/obese postmenopausal women not using hormone-replacement therapy

안유나 Graduate School, Yonsei University 2014 국내석사

Controversy remains regarding whether there is an association between circulating lipoprotein-associated phospholipase A2 (Lp-PLA2), cytokines, and oxidative stress in healthy postmenopausal women. We investigated the influence of age on Lp-PLA2 activity in postmenopausal women not using hormone therapy, and the relationship of Lp-PLA2 enzyme activity to serum cytokine levels and oxidative stress indices. Normal weight (n=1284) and overweight/obese (n=707) postmenopausal women not using hormone therapy were categorized into five age groups: 50?54, 55?59, 60?64, 65?69, and 70?89 years. Overweight-obese women showed higher plasma Lp-PLA2 activity, urinary 8-epi-prostaglandin F2α (8-epi-PGF2α), serum interleukin (IL)-6, and smaller LDL particles than normal-weight women after adjusting for age, years post-menopause, smoking, drinking, blood pressure, glucose, insulin, lipid profiles, BMI, and waist circumference. Overweight/obese women 70?89 years old showed higher Lp-PLA2 activity than those aged 50?54 years, whereas no significant difference in Lp-PLA2 activity existed across normal-weight female age-groups Overweight/obese women aged ≥65 years showed higher Lp-PLA2, oxidized LDL (ox-LDL), IL-6, and 8-epi-PGF2α than age-matched normal-weight controls. Overweight/obese women aged ≥70 years had higher ox-LDL levels than those aged 50?59, and overweight/obese women aged 65-89 showed higher IL-6 and 8-epi-PGF2α. There were strong positive correlations between Lp-PLA2 and ox-LDL (r=0.385, P<0.001), Lp-PLA2 and IL-6 (r=0.293, P<0.001), and ox-LDL and IL-6 (r=0.303, P<0.001) in overweight/obese women; however, these relationships were weak in normal-weight women. These results demonstrate enhanced oxidative- and inflammatory mediator-associated Lp-PLA2 activity in overweight/obese postmenopausal women not using hormone therapy.

Association of LUC7L2 Polymorphisms with Overweight/Obesity in Korean Population

박윤철 경희대학교 대학원 2010 국내석사

이 단면연구의 목적은 LUC7L2의 단일염기다형성과 과체중/비만의 관계에 대해 밝히는 것이다. Illumina BeadStation 500 GX의 Golden Gate assay를 사용하여 LUC7L2가 11개의 단일염기다형성(rs4398844, rs6962637, rs6963867, rs7783619, rs9640925, rs10242419, rs4732374, rs3778931, rs13068, rs1127424, and rs9683)의 유전자형을 가지고 있음을 밝혀낼 수 있었다. 한국에 거주하는 200명의 정상체중그룹(BMI<23)과 245명의 과체중/비만그룹(BMI≥23)을 대상으로 하였고, 유전자분석을 위해 Helixtree, SNPStats, and Haploview programs을 사용하였다. 모든 11개의 단일염기다형성 유전자는 하디-바인베르크 평형의 법칙에 잘 적용되었다. 이 단일염기다형성 유전자 중에 8개의 단일염기다형성 유전자들(rs6963867, rs7783619, rs9640925, rs10242419, rs4732374, rs13068, rs1127424,and rs9683)이 과체중 및 비만과 관련이 유의하게 있는 것으로 나타났다. Haploview program을 사용하여 실시한 Haplotype 분석에서 한 개의 LD 블록을 설정하였다. 2개의 Haplotype은 8개의 유의미한 단일염기다형성 유전자들을 포함하고 있는 것으로 밝혀졌다. 이 결과는 과체중/비만 그룹과 정상인 그룹 간의 Haplotype이 유의한 차이가 있다는 것을 보여주고 있다(haplotype GGTGGGGAGAT: frequency=0.788, 2=4.91, p=0.0267, and haplotyope AAGAAACGCGA: 0.203, 5.37, 0.0205). 이 연구는 8개의 단일염기다형성 유전자들(rs6963867, rs7783619, rs9640925, rs10242419, rs4732374, rs13068, rs1127424, and rs9683)과 LUC7L2 유전자의 두 개의 Haplotypes(GGTGGGGAGAT and AAGAAACGCGA)이 한국인의 비만과 관련이 있다는 사실을 밝히고 있다. Objectives : The aim of this cross-sectional study was to identify the relationship between single nucleotide polymorphisms (SNPs) of LUC7-like 2 (S. cerevisiae) (LUC7L2) and overweight/obesity. Methods : Eleven SNPs (rs4398844, rs6962637, rs6963867, rs7783619, rs9640925, rs10242419, rs4732374, rs3778931, rs13068, rs1127424, and rs9683) of the LUC7L2 region were genotyped, using Golden Gate assay on an Illumina BeadStation 500 GX. Two hundred normal (BMI <23) and 245 (BMI ≥23) overweight/obese groups were analyzed. For the analysis of genetic data, Helixtree, SNPStats, and Haploview programs were used. Results : All eleven SNPs tested in this study were compatible with Hardy-Weinberg equilibrium expectation. Of these SNPs, eight polymorphisms (rs6963867, rs7783619, rs9640925, rs10242419, rs4732374, rs13068, rs1127424,and rs9683) proved to have significant association with overweight/obesity. In haplotype analysis using Haploview program, one linkage disequilibrium block was constructed. Two haplotypeswere identified containing the eight significant polymorphisms. The result showed that these haplotypes were significantly different between control and overweight/obese groups (haplotype GGTGGGGAGAT: frequency=0.788, 2=4.91, p=0.0267, and haplotyope AAGAAACGCGA: 0.203, 5.37, 0.0205). Conclusions : This study suggests that eight polymorphisms (rs6963867, rs7783619, rs9640925, rs10242419, rs4732374, rs13068, rs1127424, and rs9683) and two haplotypes (GGTGGGGAGAT and AAGAAACGCGA) of LUC7L2 may be associated with obesity in Korean people. Key words : Haplotype, LUC7L2, Obesity, Overweight, Single nucleotide polymorphism

Metabolites in the regulation of visceral fat obesity and atherogenic traits in the overweight

이난희 Graduate School, Yonsei University 2016 국내석사

연구목적 : 본 연구는 대사적으로 건강한 과체중군 (MHO)과 대사적으로 건강하지 않은 과체중군 (MUO)에서 내장지방 비만과 죽상동맥경화 특성을 조절하는 대사체를 규명하는 것에 목적이 있다. 연구방법 : 본 연구는 횡단적 단면연구로 (cross sectional study) 과체중(25.0kg/㎡ ≤ BMI <30.0kg/㎡)인 성인 112명이 참여했다. 건강한 과체중군과 건강하지 않은 과체중군의 대사적 변화는 UPLC LTQ-Orbitrap MS을 기반으로 알아보고자 한다. 연구결과 : DEXA를 사용했을 때 측정한 총 지방량과 체지방지수의 값이 비슷했지만, MUO군이 MHO군보다 L1과 L4의 내장지방함량이 높은 것을 확인하였다. 또한 MUO군은 MHO군보다 혈압, 혈청 지질 수치, hs-CRP, 혈장 MDA, 산화저밀도지단백 (oxLDL) 그리고 HOMA-IR의 수치가 더 높았고, HDL 콜레스테롤의 양이 적음을 확인하였다. 혈장 대사체에서 MUO군이 긴 사슬 아실 카르니틴 (LC; C14:1, C16:1, C16), 중간사슬 아실 카르니틴(C12:1, C12), 우로빌리노겐 (urobilinogen), 도코사헥사엔산 (DHA), lysoPE (22:6), lysoPC (22:6), lysoPC (22:5), methoxybenzenepropanoic acid, isodesmosin 수치가 MHO군보다 높았다. 5가지 아실 카르니틴에서 내장지방산 (VFA)과 산화저밀도지단백 (oxLDL)에 양의 상관관계가 있었고, HDL 콜레스테롤과 LDL particle size에서 음의 상관관계가 있음을 확인하였다. 연구결론 : 3개의 긴사슬 아실 카르니틴과 2개의 중간사슬 아실 카르니틴을 포함한 12개의 중요 대사체는 MUO군과 MHO군을 구분하는데 중요하다. MUO그룹의 내장 지방으로부터 만성적인 지질 잔여물은 죽상동맥경화에 관련 된 대사체인 긴사슬 아실 카르니틴과 중간사슬 아실 카르니틴의 상당한 증가를 가져올 수 있다. Objective : The aim is to screen metabolomes of both metabolically healthy and unhealthy overweight subjects to identify potential metabolites that may regulate the different metabolic characteristics of overweight. Methods : We examined the metabolic characteristics of 112 overweight (25kg/m2 ≤ Body mass index (BMI) <30kg/m2) individuals aged 30-65 year. Plasma metabolomic profiling of metabolically unhealthy overweight [MUO, visceral fat area (VFA) at 4th lumbar (L4) ≥ 100cm2] and metabolically healthy overweight (MHO, L4 VFA <100cm2) individuals with matching age, gender, and BMI were performed. Results : MUO subjects showed higher VFA at 1st lumbar (L1) and L4 than MHO subjects. MUO group showed higher blood pressure, lipid profile, high-sensivity C-reactive protein (hs-CRP), malondialdehyde (MDA) and oxidized LDL (oxLDL) and homeostasis model assessment insulin resistance (HOMA-IR), and lower HDL-cholesterol. In plasma metabolite identification, MUO group showed significantly higher levels of long chain (LC; C14:1, C16:1, C16) acylcarnitines (ACs), medium chain (MC; C12:1, C12) ACs, urobilinogen, docosahexaenoic acid (DHA) (C22:6ω3), lysophospatidylethanolamine (lysoPE) (22:6), lysophospatidylcholine (lysoPC) (22:6), lysoPC (22:5), methoxybenzenepropanoic acid, and isodesmosin. All 5 ACs correlated positively VFA and oxidized LDL (oxLDL) and negatively with HDL-cholesterol and LDL particle size. Conclusions : Twelve major metabolites, including 3 LCACs and 2 MCACs, are important for distinguishing between MUO and MHO. Probably, chronic lipid surplus from visceral fat in MUO could cause substantial increase in plasma MCAC and LCAC which are closely related to atherogenic traits.

Gender-specific differences among Peruvian adults with overweight/obesity and central obesity according to insurance type

유영민 Graduate School, Yonsei University 2023 국내석사

Obesity is a global public health challenge, especially in low- and middle-income countries such as Peru. Meanwhile, Universal Health Coverage, which aims to provide access to healthcare for all citizens, is anticipated by the international community to contribute to disease prevention and management, including obesity. In Peru, governmental efforts are underway to introduce and expand insurance systems in order to achieve Universal Health Coverage. While high coverage rates have been achieved, some researchers suggest that disparities may exist in the health statuses of beneficiaries owing to differences in each insurance scheme. However, few studies have investigated the association between health insurance type and health status. Thus, this study aimed to address this research gap by exploring the relationship between insurance type and the prevalence of obesity, a condition known to be a precursor to multiple health complications. The study analyzed records from 26,676 individuals from the 2021 Peruvian Demographics and Health Survey database. Analysis of variance and chi-squared tests were used to compare the characteristics among the uninsured, Public Integral Health Insurance (SIS), and Social Security Health Insurance (EsSalud) groups. Linear and logistic regression analyses were performed to examine the association between insurance status and obesity, with adjustment for sociodemographic and comorbidity variables in the multivariate models. After adjusting for all confounding variables, it was found that EsSalud had a positive association with the overweight/obesity status in both men and women (aOR: 1.154; 95% CI: 1.062–1.254; P=0.001; aOR: 1.17; 95% CI: 1.069–1.28; P=0.001). In contrast, SIS was negatively associated with the overweight/obesity status in men (aOR: 0.823; 95% CI: 0.769–0.881; P<0.001), while it showed a slightly positive association in women (aOR: 1.098; 95% CI: 1.019–1.184; P=0.014). The primary finding was that individuals enrolled in EsSalud, Peruvian social security health insurance, were more likely to be overweight/obese than those of the other groups, contradicting the anticipated trend of lower obesity rates among insurance subscribers owing to improved healthcare access. Furthermore, male subscribers of SIS were found to be less obese compared to non-subscribers, which can be interpreted through various aspects such as geographical and cultural factors. This discrepancy can be traced back to the design of the Peruvian insurance system, which targets specific demographics based on various criteria such as occupation, income, and social class. In conclusion, the findings of this study indicate significant differences in the overweight/obesity and central obesity status of Peruvian adults based on the type of insurance coverage, and this trend varies by gender. In other countries with similar health insurance structures targeting different population segments, such as Mexico and Colombia, comparable patterns may be found, thus providing potential areas for future investigation. The results underscore the need for targeted interventions that account for disparities among different insurance groups to address obesity. 비만은 전 세계적인 보건 문제로, 페루와 같은 중소득 국가들에서 특히 중요하다. 한편, 모든 시민에게 의료 서비스 접근성을 보장하는 것을 목적으로 하는 보편적 의료보장(UHC, Universal Health Care)은 비만을 비롯한 질병의 예방 및 관리에 기여할 것으로 기대된다. 이에 따라 페루 정부는 UHC를 달성하기 위해 국가 차원에서 보험 제도를 도입하고 확장하는 노력을 기울여 왔다. 이를 통해 페루 내 건강보험 가입자 비율 증가라는 성과를 이룩하였지만, 일부 연구자들은 각 보험 제도의 특성상 가입자들의 건강 상태가 상이할 수 있음을 언급하였다. 반면 페루 내 보험 유형에 따른 가입자들의 건강 상태를 조사한 연구는 충분하지 않다. 이에 본 연구는 다양한 만성질환의 위험요인이 되는 비만의 유병률과 건강보험 유형 간의 관련성을 밝혀 이러한 문헌적 공백을 채우고자 하였다. 본 연구는 2021년 페루 인구 및 건강 설문조사 데이터베이스 내 26,676명의 기록을 분석하였다. 미가입자, 통합건강보험(SIS) 가입자, 사회보장건강보험(EsSalud) 가입자 그룹 간의 일반적인 특성은 ANOVA와 카이제곱 검정을 통해 분석하였다. 보험 상태와 비만 간의 관련성을 살펴보기 위해 선형 및 로지스틱 회귀분석을 수행하였으며, 다변량 모델에서 사회경제적 변수와 합병증 관련 변수를 보정하였다. 모든 교란 변수를 보정한 후, EsSalud 보험이 페루 남성과 여성 모두에서 과체중/비만 상태와 유의미한 양의 상관성을 보임을 발견하였다 (aOR: 1.154; 95% CI: 1.062–1.254; P=0.001, aOR: 1.17; 95% CI: 1.069–1.28; P=0.001). 반면, SIS는 남성의 과체중/비만 상태와 유의미한 음의 상관관계를 보였으며 (aOR: 0.823; 95% CI: 0.769–0.881; P<0.001), 여성에서는 미미한 양의 연관성을 보였다 (aOR: 1.098; 95% CI: 1.019–1.184; P=0.014). 이는 건강보험 가입자들이 보다 양질의 건강관리 서비스를 이용함으로써 비만률을 낮출 수 있을 것이라는 기대와는 다른 결과였다. 이런 차이는 페루의 보험 시스템이 직업, 소득, 사회 계급 등 다양한 기준에 따라 특정 그룹을 대상으로 하도록 설계되었다는 사실에서 비롯된 것일 수 있다. 연구 결과, 건강보험의 종류에 따라 페루 국민의 비만도는 유의한 차이가 있으며, 이와 관련된 상관관계는 성별에 따라 그 특성이 상이하다는 점을 알 수 있다. 멕시코 및 콜롬비아와 같이 사회경제적으로 각기 다른 특성을 지닌 인구 집단을 대상으로 하는 유사한 건강보험 구조를 가진 다른 국가에서도 비슷한 패턴이 발견될 수 있으며, 이는 앞으로의 후속 연구에서 다루어질 수 있다. 본 연구는 다른 보험 그룹 간 가입자 특성의 차이를 고려하여 비만의 예방 및 관리를 위한 맞춤형 개입이 필요하다는 점을 시사한다.

Influence of household environment and food security on children's physical growth

김지현 서울대학교 보건대학원 2015 국내석사

Background The guardians’ care and the amount and quality of resources are crucial for managing young children’s growth. However, gap in growth between children with different household environment still remains as major public health concerns among young Korean children who are facing rapid social changes. Considering that children’s growth is ultimately defined by the amount and quality of nutrition, the effect of household food security on children’s growth and interaction between their household environments should be studied Objective This study aimed to identify the transition of children’s stunted growth and overweight growth between 2009 and 2012. The relationship between household food security and household income level was studied. In addition, the influence of parental socioeconomic status (SES) and child care environment and how it is changed by the food security in the household were analyzed. Methods This study used the 4th (2009) and 5th (2010-2012) Korean Health and Nutritional Examination Surveys for data. Study participants were children aged 24 to 60 months old, except the one who had missing height or weight information or diagnosed with congenital heart disease. The significant influence of household income level on household food security was analyzed using logistic regression after controlling such variables as the characteristics of the head of the household, family member, household type, and external assistance related to food supplement or child care. Household food security reflecting household’s nutritional environment and economic circumstances, parental SES except household income level, and child care environment were used as the independent variables in the study of the influence of household environment on children’s physical growth. The 2006 World Health Organization’s Children Growth Standards was used to identify normal and abnormal height and weight. A two-stage stratified systematic sampling method was applied in both logistic regression analyses. Results The prevalence of stunted growth was lower than 2% in each year but the prevalence of overweight growth was higher than that of stunted growth in each year and the annual changes of the prevalence of overweight was more rapid to that of stunted growth. Household income level had a significant influence on determining household food security; the lower the household income, the more the household is likely to be in a food insecure status. Household food security, parental SES and child care environment exerted significant effects on both children’s height and weight. In particular, household food security, mothers’ educational level, and the use of child care facility were the most influential factors to children’s stunted growth, while the frequency of having meals with family member was distinctively significant to children’s overweight growth. Household food security and mothers’ educational level remained as the most influential factor on children’s stunted growth in all of the study models that applied interaction terms. In contrast, the frequency of having meals with family member remained as significant factor to children’s overweight growth after applying interaction between household food security and household environment. However, there were no significant interaction terms between household food security, parental SES, and child care environment. Conclusions This study demonstrated that food secured environment, mothers’ educational level, and caregivers’ responsive care were important variables for young children’s normal growth. Therefore, multidimensional reviews of children’s household environments should be considered in child growth study. National policy in regard to child care assistance should take an approach in researching children’s nutritional environment and providing child care assistance service programs to household in food insecure status.

Changes of body composition and metabolic parameters by lifestyle modification according to FTO SNPs among overweight and obese Korean adults

김채린 동아대학교 대학원 2023 국내석사

This study aimed to investigate if the changes of anthropometric measurements and metabolic parameters after the lifestyle modification are different according to FTO single nucleotide polymorphisms (SNPs) among overweight and obese Korean adults. Study participants were recruited through a public advertisement. After the screening of 60 people, 43 adults who were overweight/obesity (BMI ≥ 23 kg/m²) were enrolled in the 8-week lifestyle modification. Of them, 37 followed up until the 4th week, and 34 finally accomplished the 8th week intervention. Anthropometric and biochemical parameters, and FTO SNPs (rs1421085T>C, rs9939609T>A) were analyzed. Interestingly, study participants show the same pattern in the genotype of both SNPs in the FTO (rs1421085T>C: TT, n=28, TC n=9; rs9939609T>A: TT, n=28, TA, n=9). At baseline, proportions of sex and BMI categories were not significantly different, but visceral fat area and serum C-peptide levels were significantly higher, and fasting glucose and HDL-cholesterols were lower in the subjects with minor allele (minor allele carriers) than those with wild types. After 4-week, wild type group had significant reduction in BMI, blood pressure, subcutaneous fat area (SFA), glycated hemoglobin (%), and fasting glucose, minor allele carriers had significant reduction only in glycated hemoglobin (%), and fasting glucose. After the 8-week, both genotype groups had significant improvement in BMI and waist circumference and SFA. After 8-week, wild type group showed improvement in the shift of overweight/obesity category (38.5%), but minor allele carrier group did not show the shift (0.0%) (P = 0.037), even though the last group had significant improvement in the changed values of the parameters. This present study shows that changes of anthropometric measurements and metabolic parameters after the lifestyle modification are associated with the genotype of the FTO SNPs among overweight and obese Korean adults. Further intervention studies with large scaled population are needed to support the results and conclusion of this study. 본 연구는 과체중·비만 한국 성인을 대상으로 식생활 개선 프로그램을 통하여 인체계측 및 대사 지표 변화와 FTO 유전자의 단일염기다형성 (SNPs, single nucleotide polymorphisms)과의 연관성에 대하여 알아보고자 하였다. 연구 참여자는 공개 광고를 통해 모집되었다. 60명을 모집한 후, 과체중/비만(BMI ≥ 23 kg/m²) 성인 43명이 8주간의 식생활 개선 프로그램에 등록되었다. 연구 참여자 37명이 4주차까지 완료하였고, 최종적으로 34명이 8주차까지 완료하였다. 인체계측 및 생화학적 지표 수준과 FTO SNPs (rs1421085T>C, rs9939609T>A)을 분석하였다. 연구 참여자들은 흥미롭게도 FTO 유전자 내 2가지 SNP의 유전자형에서 동일한 패턴을 보여주었다 (rs1421085T>C: TT, n=28, TC, n=9; rs9939609T>A: TT, n=28, TA, n=9). 0주차에서 성별과 BMI에 따른 유전자형의 비율은 유의한 차이가 없었지만, minor allele carriers 그룹이 wild type 그룹보다 내장지방 면적과 혈청 C-peptide 수치가 유의하게 더 높았고, 공복 혈당과 HDL콜레스테롤 수치는 더 낮았다. 중재 4주 후 wild type 그룹은 BMI, 혈압, 피하지방 면적, 당화혈색소(%) 및 공복혈당 수준이 유의적으로 감소하였고, minor allele carriers 그룹은 당화혈색소(%)와 공복혈당 수준이 유의적으로 감소하였다. 중재 8주 후 두 유전자형 그룹 모두 BMI, 허리둘레 및 피하지방 면적 수치가 크게 개선되었다. 또한 중재 8주 후 wild type 그룹은 과체중/비만도 카테고리가 개선되었지만 (38.5%), minor allele carriers 그룹은 비만 관련 체구성 지표 수준이 개선되었음에도 불구하고 과체중/비만도 카테고리의 변화 (0.0%)를 나타내지 않았다 (P = 0.037). 본 연구는 식생활 습관 중재 후 과체중·비만 한국 성인의 FTO SNPs 유전자형과 인체 계측치 및 대사 지표 변화와의 연관성을 확인하였다. 그러나 이 연구의 결과와 결론을 뒷받침하기 위해서는 대규모 인구를 대상으로 한 추가 개입 연구가 필요할 것으로 보인다.

Influence of plasma fatty acid profiles and dietary medium-chain diacylglycerol on cardiometabolic risk : 4 year's follow-up and crossover designed studies

이아영 Graduate School, Yonsei University 2018 국내박사

심혈관계 질환의 위험도를 상승시키는 비만은 한국인의 주요 건강 문제로 인식되고 있으며, 혈중 지방산 및 중성지방의 지질변화와 밀접 한 상관관계가 있다. 지방산 대사의 이상, 증가된 혈중 지방산 및 중성 지방 수치는 비만인 사람들에게서 발견된다. 혈중 지방산 프로파일은 식이지방 섭취를 통한 지방산 구성성분과 체내 지방산 대사와 관련 있 는 내인성 지방산 합성을 반영한다. 또한 혈중 중성지방의 수준은 식이 섭취를 통한 지방의 영향을 주로 받으며, 증가된 식후 중성지방의 수치 는 비만의 발생과 관련이 있다. 흥미롭게도 과체중/비만인 사람들 중에 서 정상범위의 대사적 프로파일을 나타내는 사람들이 있으며, 이들을 “대사적으로 건강한 과체중/비만”으로 일컫는다. 더 나아가, 과체중/ 비만인 사람들의 대사적인 건강상태의 변화는 심혈관계 질환 위험도 상 승에도 영향을 미친다. 이처럼 과체중/비만은 심혈관계 질환의 위험도 를 상승시키는 요인으로 작용할 수 있기 때문에, 비만을 예방하기 위한 식이 소재에 대한 연구가 필요하다. 특히, 앞서 언급한 식후 중성지방 및 혈중 지방산의 수준은 비만 발생과 관련이 있기 때문에, 이들을 억 제하기 위한 식이 소재의 연구가 요구된다. 따라서 본 논문은 (1) 대사 적으로 건강한 과체중 대상자의 4년간의 추적연구를 통해서 대사적 건 강상태의 변화와 혈액 내 지방산 및 혈관경직도의 변화와의 상관관계를 연구하고, (2) medium-chain diacylglycerol(MCDG)를 함유한 기능성 유 지의 식후 중성지방 및 지방산 상승 억제 효과를 평가하고자 하였다. 4년간의 추적연구에서는, 대사적으로 건강한 과체중 대상자의 4년 후 대사적 건강 상태의 변화와 혈액 내 지방산 및 혈관경직도의 변화와 의 상관관계를 연구하였다. 대사적으로 건강한 과체중 대상자 92명을 추적 연구하여 두 집단으로 구분하였다. 4년 후에도 대사적으로 건강한 과체중 대상자는 MHO군으로 명명하였으며 총 58명이였다. 반면, 대사적 으로 건강한 과체중에서 4년 후에 대사적으로 건강하지 않은 과체중으 로 발전한 대상자는 모두 34명이였으며 MUO군으로 명명하였다. 상환 발 목 맥파속도(ba-PWV)와 혈액 내 지방산은 4년 전후로 모두 측정되었다. MUO군은 MHO군에 비해서 몸무게, 허리둘레, 혈당, 인슐린, 중성지방, 상환 발목 맥파속도가 유의적으로 증가하였으나, HDL 콜레스테롤은 유 의적으로 감소한 결과를 나타내었다. 또한 MUO군에서 총 14개의 지방산 이 MHO군에 비해서 증가하였다. MHO군은 MUO군에 비해서 △5- desaturase이 증가한 반면 MUO군은 C16 △9-desaturase가 증가하였다. 다중선형회귀분석을 통해, 상환 발목 맥파속도의 변화량이 수축기 혈압 의 변화량, C16:1n-7 (palmitoleic acid)과 C18:1n-9 (oleic acid)의 변화량, C16 △9-desaturase의 변화량과의 상관관계가 있음을 분석할 수 있었다. 결론적으로 4년간의 추적연구를 통해서 대사적인 건강상태 의 변화가 혈액 내 지방산 및 혈관 경직도의 변화와 밀접한 상관관계가 있음을 밝힐 수 있었다. 교차설계연구에서는, MCDG를 함유한 기능성 유지의 식후 중성지방 및 지방산 상승 억제 효과를 평가하기 위하여 이중눈가림, 무작위배정, 교차시험으로 연구가 진행되었으며 long-chain triacylglycerols (LCT) 을 함유한 유지와 비교하여 그 효과를 평가하였다. 건강한 정상체중의 대상자 28명은 본 연구를 위해 총 2번 방문하였으며, MCDG와 LCT가 15g 포함된 머핀을 각각의 방문에서 한번씩 모두 섭취하였다. 매 방문에서 공복 (0시간)과 머핀 섭취 2, 3, 4, 6시간 후에 혈액을 채취하였다. MCDG가 함유된 머핀은 LCT가 함유된 머핀에 비해 섭취 3시간과 4시간 후의 중성지방 수치가 유의적으로 감소하였다. 유사하게도 MCDG가 함유 된 머핀은 LCT가 함유된 머핀에 비해 섭취 4시간 후의 킬로미크론 중성 지방의 수치가 유의적으로 감소하였다. 식후 중성지방과 킬로미크론 중 성지방의 그래프 아래의 면적 (area under the curve; AUC)은 LCT가 함 유된 머핀 섭취에 비해 MCDG가 함유된 머핀 섭취에서 13% 더 낮게 측정 되었다. 식후 혈액 내 지방산 (palmitic acid, stearic acid, linoleic acid)의 상승은 LCT가 함유된 머핀 섭취에 비해 MCDG가 함유된 머핀 섭 취에서 그 수치가 낮게 측정되었다. 본 연구를 통해서 MCDG의 섭취가 LCT의 섭취에 비해서 식후 중성지방혈증을 감소시키는 결과를 밝힐 수 있었다. 결론적으로, “대사적으로 건강한 과체중/비만”인 사람들은 생활방식(특히, 체중증가와 식이지방의 섭취 증가와 관련된 생활방식)에 따라서 심혈관계 질환의 위험도를 상승시키는 “대사적으로 건강하지 않은 과체중/비만”의 표현형으로 발전될 수 있다. 따라서 대사적인 표현형의 개선 및 잠재적인 질병의 부담을 줄이기 위해서 에너지 소비의 증가와 식이지방 섭취의 감소는 필요하다. 또한 “대사적으로 건강한 과체중/비만”표현형은 몸무게와 허리둘레를 관리함으로써 그 표현형을 유지할 수 있다. 식이지방의 섭취를 줄이는 것 외에도, MCDG 를 함유한 기능성유지 (식이지방 대체 소재)의 섭취는 혈중 지질 프로파일을 개선시키는데 도움이 되며, MCDG 의 지방산 구성 성분과 소화기관에서의 대사적 특징 덕분에 중성지방 대사와 관련 있는 인슐린 저항성과 대사증후군의 예방에 긍정적인 효과를 나타낼 것으로 기대된다. Obesity, which increases the risks of cardiovascular diseases (CVD), is one of the major health issues among Korean. The prevalence of obesity is associated with blood lipid alterations such as fatty acid and triglycerides (TG). In obese individuals, there are several abnormalities of free fatty acid metabolism and increased levels of blood fatty acids and TG. Plasma fatty acid profiles reflect the fatty acid composition of dietary fat and the endogenous fatty acid synthesis. Increased postprandial TG levels, which are mainly influenced by dietary fat, are involved in the development of obesity. Interestingly, there is a subgroup of overweight/obese individuals with normal metabolic features, described as “metabolically healthy overweight/obesity”. Further, changes in metabolic health status in metabolically healthy overweight/obese individuals influence an increased risk of CVD, hence there is a need for the study of dietary fat substitutes to prevent obesity. Especially, increased postprandial triglyceride and plasma fatty acid levels as described above are associated with the development of obesity. Therefore, the study of dietary fat substitutes lowering postprandial TG and fatty acid levels is needed. Accordingly, the objectives of this study were conducted in two parts: (1) to examine the relationships between the changes in metabolic health status and the changes in plasma fatty acids and arterial stiffness in metabolically healthy overweight (MHO) participants over a 4-year period; and (2) to assess the ability of a novel lipid structure including medium-chain diacylglycerol (MCDG) oil to lower postprandial TG and plasma fatty acid levels under a crossover design. In the first part, the 92 MHO participants recruited in the cohort study were divided into 2 groups: the MHO-maintained group (n=58) and the metabolically unhealthy overweight (MUO)-developed group (MHO at baseline but developed incident MUO during the 4-year follow-up; n=34). Brachial-ankle pulse wave velocity (ba-PWV), which is an index of arterial stiffness, and plasma fatty acids were measured at baseline and after 4 years. Compared with the MHO-maintained group, the MUO-developed group showed a trend toward an increase in fat intake. The MUO-developed group showed greater increases in body weight, waist circumference, glucose, insulin, TG and ba-PWV as well as a greater reduction in HDL cholesterol than the MHO-maintained group. Compared to the MHO-maintained group, the MUO-developed group showed greater increases in 14 plasma fatty acids. In addition, the MHO-maintained group showed a greater increase in △5-desaturase than the MUO-developed group, whereas the MUO-developed group showed a greater increase in C16 △9-desaturase. Multiple linear regression revealed that changes in ba-PWV were correlated with changes in systolic blood pressure, C16:1n-7 (palmitoleic acid), C18:1n-9 (oleic acid), and C16 △9-desaturase (standardized β=0.914, p<0.001). Consequently, this study found a close relationship between changes in metabolic health status and those in plasma fatty acids and arterial stiffness over the 4-year study period. In the second part, the double-blind, randomized, crossover trial evaluated the effects of an oral fat load containing MCDG compared with equivalent intakes of longchain triacylglycerols (LCT) on the postprandial metabolic responses of healthy men and women with normal weight (n=28). During two visits, each subject consumed a single oral fat load on each test day. The fat loads were delivered in muffins that contained 15 g of one of the two test oils. Blood samples were collected in a fasting state (0 hr) and at 2, 3, 4, and 6 hrs after ingestion of the muffin. Mean TG levels were lower at 3 (P=0.019) and 4 hr (P=0.023) after the consumption of MCDG muffin, compared to LCT muffin. Similarly, the mean chylomicron-TG levels were lower at 4 hrs (P=0.033) after the consumption of MCDG muffin, compared to LCT muffin. Both the postprandial TG and chylomicron-TG incremental areas under the curve after the consumption of MCDG muffin were 13% lower, compared with the response after the consumption of LCT muffin. Postprandial elevations in plasma levels of palmitic acid, stearic acid and linoleic acid were much smaller at the MCDG muffin consumption than the LCT muffin consumption. This study verified that dietary MCDG decreased postprandial triglyceridemia compared with LCT. In conclusion, the MHO can develop into MUO phenotype associated with accelerated arterial stiffness, depending on one’s lifestyle (especially with regard to weight gain and increased dietary fat intake). Thus, there must be an increase in energy expenditure and a reduction in dietary fat intake, to improve metabolic phenotype and reduce potential disease burden. Further, the MHO phenotype can be sustained by maintaining healthy body weight and waist circumference. In addition to reducing dietary fat intake, the intake of MCDG, a dietary fat substitute, can improve lipid profiles. The intake of MCDG can be a potential method for preventing TG metabolism related to the insulin resistance/metabolic syndrome, due to its metabolic characteristics in the digestive tract and/or different fatty acid composition.

Mild weight loss reduced inflammatory cytokines, leukocyte count and oxidative stress in overweight and moderately obese subjects treated for 3 years with dietary modification

최용인 The Graduate School of Yonsei University 2012 국내석사

Objective: The aim was to examine whether a diet-induced long-term mild weight reduction results in improvement in proinflammatory cytokines, leukocyte count and oxidative stress. Methods: One hundred twenty two overweight/obese subjects (25≤BMI<34) aged 30-65 (30-59) yr participated in a clinical intervention study lasting 3 years including a daily energy deficit of 100kcal. Weight loss was defined as successful when the initial body weight decreased by at least 2kg after a 3-year period of clinical intervention. Results: In the successful mild weight loss group (n=50), the change in body weight was 5.4% (-4.16±0.31 kg), whereas in the unsuccessful weight loss group (n=49) the change was 0.05±0.14 kg. After 3 years, successful weight loss group showed a significant decrease in insulin, triglyceride, total- and LDL-cholesterol, free fatty acids and leukocyte count (P=0.030). Serum concentrations of IL-1β and IL-6 and urinary excretion of 8-epi-PGF2α were significantly reduced following successful weight loss, by 45%, 30% and 14%, respectively. However, the unsuccessful weight loss group showed a significant increase in body fat percent and waist circumference, oxidized LDL and TNF-α, and a significant decrease in HDL-cholesterol. After adjusting for baseline values, the changes in body fat %, waist circumference, insulin, leukocyte count (P=0.018), IL-6 (P=0.031), IL-1β (P<0.001) and TNF-α (P<0.001) and urinary excretion of 8-epi-PGF2α (P=0.036) were significantly different between successful and unsuccessful weight loss groups. In all subjects, there was a positive correlation between changes in IL-1β and urinary 8-iso-PGF2α (r=0.435, P<0.001) as well as between changes in IL-6 and urinary 8-iso-PGF2α (r=0.393, P<0.001). Conclusion: This study demonstrates beneficial effects of long-term mild weight loss on inflammatory cytokines, leukocyte counts and oxidative stress. Additionally, we found a significant correlation between the changes in proinflammatory cytokines and urinary 8-iso-PGF2α. This study, therefore, suggests that enhanced oxidative stress driven by inflammatory triggers in overweight and obesity could be, at least in part, reversible with a long-term mild weight loss.

Three Essays on Internal Migration and Risk Factors for Non-communicable Diseases (NCDs) in Low- and Middle-Income Countries (LMICS)

Li, Weilong ProQuest Dissertations & Theses University of Penn 2022 해외박사(DDOD)

Low- and middle-income countries (LMICs) have been experiencing extensive internal migration, which is closely associated with the increasing prevalence of risk factors for non-communicable diseases (NCDs). In this dissertation, I study the impact of internal migration on main NCD risk factors across three diverse LMIC contexts: China, Indonesia, and Malawi. In Chapter 1, I introduce the background, motivation, and research goals of this dissertation. In Chapter 2, I use data from the 2011 China Health and Retirement Longitudinal Study (CHARLS) to examine the associations between rural-urban migration and three main NCD risk factors, hypertension, obesity, and abdominal obesity, among older adults aged 45 or above. I find that rural-urban migrants have significantly higher chances of getting all three risk factors than rural non-migrants, suggesting a negative impact of rural-urban migration on health outcomes. Meanwhile, the number of years lived in cities significantly predicts being hypertensive, implying a “years since migration (YSM)” effect. In addition, health-related behaviors examined play a very limited role in mediating the association between migration and health. In Chapter 3, using data from the fourth and fifth waves of the Indonesia Family Life Survey (IFLS), I study the impact of rural-urban migration on overweight status in Indonesia. I find that rural-urban migration is significantly associated with being overweight, and the association is significantly stronger among women than men, demonstrating a gender disparity in health. Moreover, the number of years lived in cities does not predict overweight status, and health behavioral factors still explain little of the association between migration and health. In Chapter 4, I use data from the 2008 and 2019 waves of the Malawi Longitudinal Study of Families and Health (MLSFH) to investigate the impact of internal migration, not only rural-urban but also rural-rural, on weight status in Malawi. I find that rural-urban and rural-rural migration are both significantly associated with increased Body Mass Index (BMI) and that rural-rural migration significantly predicts being overweight. Meanwhile, the impact of rural-rural migration is significantly stronger among women than men, showing a gendered impact of migration on health. In Chapter 5, I summarize findings from the three main chapters and discuss their implications for policymaking and future research.

5 년간 비만도의 변화와 비만 관련 요인들과의 관계

서동훈 연세대학교 대학원 2007 국내석사

Objective:(1) To confirm obesity-related-factors served changing Non Overweight children(NOW) to Overweight children(OW) (2) to confirm obesity-related-factors served changing OW to NOW.Design and subjects:6 elementary schools in Seoul, 6th grade students, 1059( male 573, female 486)Measurements:Weight and height, a validated Korea translation of the Rogenberg(1965) Self esteem scale, weekly TV viewing, weekly physical activity and weekly computer use were reported by children.Results:(1)Changing NOW to OW after 5years was not related to self esteem, physical activity, TV viewing and computer use. It was associated with upper normal BMI. In BMI <15 percentile group, the odds ratio of 50≤BMI<85 percentile group was 2.448(95% CI: 1.076 ~ 5.570, P<0.05) in male and 9.29(95% CI: 2.11 ~ 40.82, P<0.005) in female.(2)Changing OW to NOW after 5years was not related to self esteem, physical activity, TV viewing and computer use, too. It was associated with slightly overweight. In BMI≥95percentile group, the odds ratio of 85≤BMI<90 percentile group was 7.019(95% CI:2.56 ~ 19.23, P<0.0005) in male and 15.349(95% CI:4.11 ~ 57.38, P<0.0001) in female.(3) 40% children of 6th grade OW were NOW before 5years, but 30% children of 1st grade NOW were OW after 5 years.Conclusion:This study confirms the association between BMI change and BMI itself. Degree of BMI is most important in changing BMI. We should care the upper normal BMI children not to be OW and help OW decrease BMI properly and slowly. 본 연구는 비만도의 증가 혹은 감소한 집단과 심리사회적인 특성 과 생활습관과의 관계를 파악하여 비만 아동 건강관리의 올바른 방 향을 모색해 보고자 5 년간의 체질량지수 변화에 따라 연구 대상 아 동을 분류한 후, 비과체중 아동이 과체중으로 진행되는데 관계하는 요인과 과체중 아동이 비과체중으로 개선되는데 관계하는 요인을 파 악하기 위하여 시행되었다.본 연구의 대상은 서울시에 위치한 6개의 초등학교 6학년 남자 573명, 여자 486명 총 1059명이었다.비만 관련 요인을 측정하기 위하여 심리사회적 요인은 Rogenberg (1965)의 자아존중감 척도를 이용하여 측정하였고, 생활습관의 차이 를 파악하기 위해 주간 TV 시청시간, 주간 컴퓨터 사용시간, 주간 운 동 시간을 설문을 통해 조사하였다.본 연구의 결과는 다음과 같다.1. 1학년 비과체중 아동이 5년후 과체중으로 진행되는데 심리 사 회적 요인, 주간 TV 시청시간, 주간 컴퓨터 사용시간, 주간 운동시 간은 관련이 없었고 아동의 체질량지수가 통계학적 의미가 있는 요인 이었다. 체질량지수 15백분위수 미만인 군을 기준으로 하였을 때 체 질량지수가 50백분위수 이상 85백분위수 미만인 군의 비차비가 남아 의 경우는 2.448(95% CI:1.076 ~ 5.570, P<0.05) 이었고 여아의 경 우는 9.290(95% CI:2.11 ~ 40.82, P<0.005)였다.2, 1학년 과체중 아동이 5년후 비과체중으로 개선되는데 심리사 회적 요인, 주간TV 시청시간, 주간 컴퓨터 사용시간, 주간 운동 시 간은 관련이 없었고 아동의 체질량지수가 통계학적인 의미가 있는 요 인이었다. 체질량지수 95백분위수 이상인 군을 기준으로 하였을 때 체질량지수가 85백분위수 이상 90백분위수 미만인 군의 비차비가 남 아의 경우는 7.019(95% CI:2.56 ~ 19.23, P<0.0005) 이었고, 여아 의 경우 15.349(95% CI:4.11 ~ 57.38, P<0.0001)였다.3, 6학년 과체중 아동 중 40%에 해당하는 아동이 1 학년 때는 비 과체중이었고, 1학년 과체중 아동 중 30%가 5년 후 정상체중으로 개 선되었다.이상의 결과로 볼 때, 과체중 아동이 정상체형이 되는 것과 비과 체중 아동이 과체중 아동이 되는 것에 가장 크게 영향을 미치는 요인 은 체질량지수가 어느 정도에 해당하는가에 있었다.