군 장병 비만관리에 대한 비교제도론적 고찰 : 미국, 캐나다, 영국 사례를 중심으로

이우진 연세대학교 대학원 2023 국내석사

Obesity is classified by the WHO as a disease and acts as a cause of foreign affairs problems, physical, emotional, and social diseases. The prevalence of adult obesity at home and abroad continues to increase, and it is showing the same trend worldwide. The increase in the country's obesity prevalence is also accompanied by an increase in the obesity prevalence in the country's defense, especially in Korea, which is conscripted, and the United States, Canada, and the United Kingdom, which implement recruitment systems, continue to see an increase in the obesity prevalence in the military. In the case of Korea, obesity is managed at the national level through the National Obesity Management Comprehensive Measures. Obesity acts as a factor that weakens the health and physical strength of soldiers. The health and physical strength of soldiers are essential to achieve the purpose and duty of soldiers, and the deterioration of health and physical strength is also a factor directly linked to the weakening ofmilitary combat power. Accordingly, military obesity management is now accepted as essential, not an option, and many countries are implementing obesity management based on related laws and systems for military obesity management and health promotion. In Korea, the military obesity management is not a hot topic as much as the smoking cessation project, and in the case of smoking cessation, Regulation is required to report on the implementation of the campaign and the implementation of the smoking cessation program. According to the results of the comparative analysis, measures to improve the military obesity management system in Korea were derived by improving the legal and institutional basis, establishing an integrated health promotion center, expanding the number of people in charge of obesity management, implementing ICT obesity management program, and establishing a evaluation system. Based on previous studies on obesity management and comparative analysis of obesity management system in three countries, this study reviewed the necessity of obesity management, the necessity of establishing a legal and institutional foundation for obesity management, and guidelines for consistent operation of obesity management system. If this paper is applied to the military situation in Korea and needs to be improved, it is hoped that it will help to establish a legal and institutional foundation and implement system more efficiently, and it will be an opportunity to improve the health level of the Korean people through obesity management. 비만은 WHO가 질병으로 분류했으며 외모 문제, 신체적, 정서적, 사회적 질환 발생의 원인으로 작용한다. 국내 성인 비만 유병률은 지속해서 증가하고 있으며 세계적으로도 동일한 추세로 나타나고 있다. 국가의 비만유병률 증가는 국가를 방위하는 군에서의 비만유병률 증가도 동반하고 있는데 징집을 하는 우리나라를 비롯해 모병제를 시행하는 미국, 캐나다, 영국도 지속해서 군 내 비만 유병률 증가를 문제로 보고 있다. 우리나라의 경우 「국민건강증진종합계획」,「국가 비만관리 종합대책」을 통하여 국가 차원에서 비만을 관리하고자 하고 있다. 비만은 군인의 건강과 체력을 악화시키는 요인으로 작용한다. 군인의 건강과 체력은 군인의 목적과 의무를 달성하기 위해 필수적이며 건강과 체력의 악화는 군 전투력의 약화로도 직결되는 요소이다. 이에 따라 군 비만관리는 이제 선택이 아닌 필수적인 것으로 받아들여지고 있고 여러 나라에서 군 비만관리를 위한 관련 법·제도, 비만관리 사업을 기반으로 비만관리를 시행하고 있다. 하지만 우리나라의 경우 군 비만관리 사업이 금연 사업만큼 제도적 기반이 마련되어 있지 않고 법·제도적으로도 금연의 경우 「군 건강증진 업무 훈령」에 제7조 금연운동으로 캠페인 시행, 금연 사업 관련 이행실태를 보고하도록 되어있으나 비만의 경우 제10조 식생활 개선 및 체중관리, 제12조 생환습관병으로 관련되어 있지만 이행실태를 따로 보고하지 않는 차이가 존재한다. 본 연구에서는 군 비만관리에 대한 선행연구 검토 및 우리나라를 포함한 3개국의 군 비만관리 사업을 살펴보고 비교분석한 내용을 토대로 군 비만관리 사업의 개선사항에 대하여 고찰하였으며, 군 비만관리의 필요성, 비만관리 관련 법·제도적 기반 마련의 필요성, 국가의 정책적 방향과 일치하는 사업 진행, 군 비만관리 사업의 통일성 있는 운영을 위한 가이드라인 등에 대하여 검토하였다. 비교분석 결과에 따라 우리나라 군 비만관리 사업 개선방안을 법·제도적 기반 개선, 통합 건강증진센터 구축, 비만관리 담당인력 확대, ICT활용 비만관리 사업 시행, 성과평가 체계 구축으로 도출하였다. 본 논문의 개선방안과 이를 고찰한 바가 우리나라 군 상황에 맞게 적용되고, 개선해야 할 부분이 있다면 이를 기반 삼아 더 효율적인 방향으로 법·제도적 기반을 갖추고 사업을 시행하는 데 도움이 되길 바라고, 군 비만관리를 통하여 우리나라 국민들의 건강수준을 한 단계 향상 시킬 수 있는 기회가 되기를 기대한다.

한국 중년 성인의 비만에 대한 유전자 변이와 식이 섭취의 상호작용 효과

곽준경 인하대학교 대학원 2023 국내석사

과도한 체지방으로 정의되는 비만은 전 세계적으로 심각한 질병이며, 대사증후군과 심혈관질환을 포함한 여러 합병증과 관련이 있다. 특히 중년층의 비만은 신경 보호 효과가 감소하여 인지 장애를 초래한다. 코로나바이러스감염증-19(COVID-19) 팬데믹 전후 비교 연구에 따르면 2020년 남성 비만 유병률은 2019년 대비 6.2% 증가했다. 최근 증거에 따르면, COBLL1 유전자가 식욕과 체중 유지에 중요한 호르몬인 렙틴의 혈장 농도와 관련이 있음을 시사한다. MMP26 유전자의 일반적인 다형성은 체질량지수, 체지방량, 제 2형 당뇨병 및 다양한 암과 관련이 있다. 식이 지방은 비만 위험에 영향을 미치는 중요한 요인이다. 고지방식은 체지방과 체중의 증가, 렙틴 감수성의 증가, 장내 미생물의 파괴, 혈중 지질의 축적과 관련이 있다. 최근 케토제닉 식이가 비만 치료에 효과가 있는 것으로 나타났다. 그러나 케토제닉 식이에 대한 연구 결과는 상반되며, 케토제닉 식이의 장기적인 효과는 불분명하다. COBLL1 유전자 변이, 식이 지방, 비만과의 연관성은 아직 보고되지 않았다. 또한, MMP26 유전자 변이, 케톤 생성비율, 비만 간의 연관성은 확인되지 않았다. 본 연구의 목적은 비만 발생에 대한 COBLL1 유전자와 식이 지방 섭취 간의 상호작용 및 MMP26 유전자와 케톤 생성비율 간의 상호작용을 규명하는 것이었다. 한국 유전체 역학 연구의 안산-안성 코호트 자료를 이용하여, 40세 이상의 한국 성인 3,055명과 3,056명이 본 연구에 포함되었다. 비만은 체질량지수 ≤25 kg/m2로 정의되었다. 식이 정보는 반정량적 식품섭취빈도 조사지를 이용하여 기반 자료에서 얻었다. 식이 지방 섭취(%에너지)는 지방(g) × 9 / 총 에너지(kcal) × 100으로 계산하였으며, 케톤 생성비율은 (0.9 × 지방(g) + 0.46 × 단백질(g) / (0.1 × 지방(g) + 0.58 × 단백질(g) + 총 탄수화물(g) – 총 식이섬유(g))로 계산하였다. 비만 발생과 관련하여 유전자 변이와 식이 섭취 간의 연관성은 다변수 콕스 비례 위험 모델을 사용하여 평가되었다. 평균 9.2년의 추적 기간 동안, 우리는 632건과 627건의 비만 사례를 기록했다. 비만에 대한 COBLL1 유전자 변이와 식이 지방의 연관성은 다음과 같다. COBLL1 rs6717858 유전자형과 비만 발생 간 유의미한 연관성은 발견되지 않았다. 남성의 경우, 지방 섭취가 가장 높은 3분위가 가장 낮은 1분위보다 비만 발생률이 41% 높았다(model 1: hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.02–1.95, P = 0.04). 남성의 경우, CT 및 CC 보인자의 지방 섭취는 비만과 긍정적인 연관성이 있었다(tertile 3: HR: 1.66, 95% CI: 1.07–2.58, P = 0.03, P-interaction = 0.52 in model 1: HR: 1.63, 95% CI: 1.04–2.56, P = 0.03, P-interaction = 0.49 in model 2). 여성의 경우, TT 보인자의 지방 섭취는 비만과 긍정적인 연관성이 있었다(model 1: HR: 1.49, 95% CI: 1.08–2.06: model 2, HR: 1.53, 95% CI: 1.10–2.13). 비만에 대한 MMP26 유전자 변이와 케톤 생성비율의 연관성은 다음과 같다. 케톤 생성비율과 비만 간 유의한 연관성은 없었다. MMP26 rs12279647 유전자형과 비만 발생 간 유의미한 연관성이 발견되지 않았다. rs12279647의 CC 보인자에서 케톤 생성비율은 비만 발생 증가와 유의한 연관성이 있었다(HR: 1.43, 95% CI: 1.02–2.02, P-interaction = 0.49 in model 1: HR: 1.46, 95% CI: 1.03–2.06, P-interaction = 0.0467in model 2). 총 에너지 섭취량을 추가하여 공변량을 조정한 후, 남성의 비만 발생에는 유의한 차이가 없었다(tertile 3: 95% CI: 0.98–2.01, P = 0.07). 여성에서 rs12279647의 CC 보인자의 1분위와 비교했을 때, TC, TT 보인자에서 케톤 생성비율의 1분위는 비만 발생률 증가와 관련이 있었다(HR: 1.47, 95% CI: 1.03–2.09, P-interaction = 0.0476). 우리는 2가지 연구에서 유전자 변이와 식이 섭취가 성별에 따라 한국인 중년의 비만 발생률에 차등적으로 영향을 미친다는 것을 발견했다. 이러한 결과는 저지방식이 COBLL1 유전자 변이가 비만 발생에 미치는 영향을 예방할 수 있음을 시사한다. 또한, 우리는 MMP26 rs12279647과 비만 간 연관성이 케톤 생성비율에 의해 수정될 수 있음을 발견했다. 따라서 우리의 연구 결과는 한국인의 유전적 요인을 고려한 개인 맞춤형 식단 전략을 개발하는 데 활용될 수 있다. Obesity, defined as excess body fat, is a serious disease worldwide. It causes several complications, including cardiovascular disease and metabolic syndrome. Obesity, especially in middle aged individuals, leads to cognitive impairment by decreasing in neuroprotective effects. A comparative study conducted before and after the coronavirus disease 2019 pandemic (COVID-19) showed that obesity prevalence in men increased by 6.2% in 2020 compared to 2019. Recent evidence suggests that COBLL1 is related to plasma leptin levels, a hormone important for appetite and weight maintenance. MMP26 is related to body mass index (BMI), fat mass, cancers, and type 2 diabetes (T2D). Dietary fat is a key factor for obesity. A high-fat diet is associated with increased in fat mass, weight, leptin resistance, destruction of the intestinal microbiome, and accumulation of blood lipids. A ketogenic diet has recently been known to be beneficial in treating obesity. However, the study results of ketogenic diet are conflicting, and the ketogenic diet’s long-term influences are uncertain. The association between COBLL1 genetic variants, dietary fat, and obesity has not yet been reported. Furthermore, no association has been established between MMP26 genetic variants, ketogenic ratio (KR), and obesity. This study aimed to identify the interactions between COBLL1 and dietary fat and between MMP26 and KR on the incidence of obesity. Using the Ansan-Ansung cohort data, 3,055 and 3,056 Korean adults ≥40 years were included. Obesity was assessed as a BMI ≥25 kg/m2. Dietary fat intake (% energy) was calculated as fat (g) × 9 / total energy (kcal) × 100. KR was calculated as (0.9 × fat (g) + 0.46 × protein (g)) / (0.1 × fat (g) + 0.58 × protein (g) + total carbohydrate (g)–total fiber (g)). Multivariable Cox proportional hazards model was used to assess the association between dietary intake and genetic variations on obesity. We documented 632 and 627 cases of obesity during an average follow-up period of 9.2 years. The following describes the association between COBLL1 genetic variants and dietary fat on obesity. There was no significant association between COBLL1 rs6717858 and obesity. In men, the highest tertile of fat intake had a 41% increased incidence of obesity than the lowest tertile of fat intake (model 1: hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.02–1.95, P = 0.04). In men with CT or CC carriers, fat intake was positively associated with obesity (tertile 3: HR: 1.66, 95% CI: 1.07–2.58, P = 0.03, P-interaction = 0.52 in model 1: HR: 1.63, 95% CI: 1.04–2.56, P = 0.03, P-interaction = 0.49 in model 2). In women with TT carriers, fat intake was positively associated with obesity (model 1: HR: 1.49, 95% CI: 1.08–2.06: model 2, HR: 1.53, 95% CI: 1.10–2.13). The following describes the association between the MMP26 genetic variants and the KR on obesity. There was no significant association between KR and obesity. There was no significant association between MMP26 rs12279647 and obesity. Among the CC carriers of rs12279647, the KR was associated with increased incidence of obesity (HR: 1.43, 95% CI: 1.02–2.02, P-interaction = 0.49 in model 1: HR: 1.46, 95% CI: 1.03–2.06, P-interaction = 0.0467 in model 2). After adjusting for covariates by adding total energy, there was no significant difference in obesity in men (tertile 3: 95% CI: 0.98–2.01, P = 0.07). In women with TC or TT carriers of rs12279647, the highest tertile of KR was associated with an increased incidence of obesity than with the lowest tertile of KR with CC carriers (HR: 1.47, 95% CI: 1.03–2.09, P-interaction = 0.0476). In two studies, we found that genetic variants and dietary intake differentially influenced obesity in middle-aged Koreans according to sex. These findings imply that a low-fat intake may protect against the influences of genetic variants of COBLL1 on obesity. Furthermore, we discovered that KR can modify the association between MMP26 rs12279647 and obesity. Therefore, our findings can be used to develop a personalized diet strategy that considers genetic factors in Koreans.

Anti-obesity effect of artemisia annua by suppressing adipocyte differentiation in high fat diet induced obesity mice model

Zhi, Xueyan Sungkyunkwan university 2019 국내석사

Obesity and related diseases are known as a global epidemic. Obesity can lead to many chronic diseases, such as fatty liver, type 2 diabetes, stroke, cardiovascular disease, and even increase the risk of some cancers and depression. The treatment of obesity with energy expenditure (fat), the bioenergetic pathway, is attractive and may be the most effective route. Artemisinic acid, which is isolated from the well-known anti-malaria herb Artemisia annua (AA) was recently shown to possess anti-adipogenic effects in vitro. In this context, we used C3H10T1/2 cells as a cell model to explore the safety (biological activity and toxicity) of rtemisia annua(AA)in vitro. To investigate the potential anti-obesity molecular mechanisms of Artemisia annua, including its transcription factors, and regulatory pathways in adipocyte differentiation and adipogenesis, and its effects on white fat browning. The effects of Artemisia annua extract on body weight, fat content, volume, blood glucose and insulin resistance were observed in obese rats induced by high-fat diet in vivo.

Probiotics inhibits adipogenesis in 3T3-L1 and attenuates high-fat-high-cholesterol diet-induced obesity in C57BL/6 Mice

박미현 Graduate School, Korea University 2017 국내석사

Obesity is one of the major causes involved in the development of metabolic diseases, in particular, cardiovascular diseases and type-2 diabetes mellitus. Increased lipid accumulation and abnormal adipocyte growth, which is increase of cell numbers and cell differentiation, have been documented as major pathological characteristics of obesity. Thus, the inhibition of adipogenic differentiation leads to prevent and suppress obesity. Recently, particular probiotic strains have been known to regulate lipid metabolism in vitro and/or in vivo. In this study, 151 strains of LAB were screened for anti-obesity effects by measuring cholesterol-lowering activity and anti-oxidant activity. Selected strains were investigated on anti-adipogenic activity, in vitro using 3T3-L1 cells. Treatment with Lactobacillus johnsonni 43121 and Lactobacillus rhamnosus 86 significantly reduced lipid accumulation and inhibited adipocyte differentiation by downregulating the adipogenic transcription factor in 3T3-L1 adipocytes. These results indicate that Lactobacillus johnsonni 43121 and Lactobacillus rhamnosus 86 can reduce fat mass by regulating adipogenesis in maturing pre-adipocytes. The anti-obesity effects of three probiotic strains were evaluated, using high-fat-high cholesterol diet-induced obese mice model. 12 weeks oral administration of L. johnsonii 43121, L. rhamnosus 86, or P. pentosaceus KID7 (1010 CFU per day) significantly improved serum lipid profile and downregulated the expression of gene related to adipogenesis and lipogenesis in epididymal WAT of HD-fed obese mice. Fecal analysis also demonstrated that three probiotic strains could modulate altered gut microbiota in the obese mice. Hence, these results collectively demonstrate that oral administration of Lactobacillus johnsonii 43121 Lactobacillus rhamnosus 86, and P. pentosaceus KID7 could prevent obesity, thereby improving metabolic health. Abnormal adipocyte growth, which is increase of cell numbers and cell differentiation, is regarded as a major pathological characteristic of obesity. Thus, the inhibition of adipogenic differentiation leads to prevent and suppress obesity. Recently, particular probiotic strains have been known to regulate lipid metabolism in vitro and/or in vivo. In this study, 151 strains of LAB were screened for anti-obesity effects by measuring cholesterol-lowering activity and anti-oxidant activity. Selected strains were investigated on anti-adipogenic activity, in vitro using 3T3-L1 cells. 3T3-L1 cells were treated with selected strain (108CFU/ml) during the differentiation process. Inhibition effect of intracellular lipid accumulation was assessed by TG analysis and Oil-red-O stain. Treatment with Lactobacillus johnsonni 43121 and Lactobacillus rhamnosus 86 significantly reduced lipid accumulation by 19.86% and 18.72, compared with differentiated 3T3-L1 adipocytes. They also inhibit adipocyte differentiation by downregulating the adipogenic transcription factor in 3T3-L1 adipocytes. Taken together, these results indicate that Lactobacillus johnsonni 43121 and Lactobacillus rhamnosus 86 can reduce fat mass by regulating adipogenesis in maturing preadipocytes. Further studies are needed to demonstrate their anti-obesity effects, in vivo. Obesity is one of the major causes involved in the development of metabolic diseases, in particular, cardiovascular diseases and type-2 diabetes mellitus. Increased lipid accumulation and abnormal adipocyte growth have been documented as major pathological characteristics of obesity. Recently, particular probiotic strains have been shown to improve obesity and metabolic syndrome. In this study, the anti-obesity effects of three probiotic strains were evaluated, using high-fat-high cholesterol diet-induced obese mice model. 12 weeks oral administration of L. johnsonii 43121, L. rhamnosus 86, or P. pentosaceus KID7 (1010 CFU per day) significantly improved serum lipid profile and downregulated the expression of gene related to adipogenesis and lipogenesis in epididymal WAT of HD-fed obese mice. In addition to, administration of probiotic strains upregulate the expression of gene related to thermogenesis and energy metabolism in BAT. Fecal analysis also demonstrated that three probiotic strains could modulate altered gut microbiota in the obese mice. Hence, these results collectively demonstrate that oral administration of Lactobacillus johnsonii 43121 Lactobacillus rhamnosus 86, and P. pentosaceus KID7 could prevent obesity, thereby improving metabolic health.

(A) dual role of sulfuretin in adipocyte, osteoclast, and osteoblast differentiation

Kim, Suji Sungkyunkwan university 2020 국내박사

Obesity is increasing in worldwide and it has various complications such as type 2 diabetes, cardiovascular disease, fatty liver and osteoporosis. Obesity lowers the quality of life and causes discomfort in social activities. Of note, increased obesity threatens public health and causes national financial losses. In order to treat such obesity and obesity-related metabolic diseases, a lot of researcher is trying to find out how to conquer obesity in various fields. Obesity is caused by energy imbalances from excessive energy accumulation (in the form of triglycerides) in whole body. The differentiation of adipocytes is largely regulated by a gene called Pparγ, a member of the nuclear hormone receptor group. Pparγ plays an important role in the regulation of transcription factors related to adipocyte differentiation with the highest expression in adipose tissue. Therefore, in this study, I tried to find a single compound that reduces the expression of Pparγ mRNA in adipocytes after separating a single compound from Rhus verniciflua extract. Screening for finding an anti-obesity compound revealed that, among eight single substances, sulfuretin reduced the mRNA expression of Pparγ and its target genes. Part 2 shows that sulfuretin decreased triglyceride accumulation in adipocytes, and reduced body weight and improved insulin sensitivity in mice. Sulfuretin induced anti-obesity effects was evaluated in cell and animal models, but underlying mechanisms were not clarified. Therefore, I listed up the genes which were upregulated in sulfuretin-treated adipocytes by using microarray assay. Among upregulated genes, Atf3 specifically reduced fat accumulation in adipocytes. Part 3 shows that Atf3 played a significant role in the inhibition of obesity in cell and animal model. When fed a high-fat diet, increased weight gain and impaired glucose metabolism were observed in Atf3 knockout mice compared to wild-type. The origin of adipocytes is mesenchymal stem cells, which also differentiate into osteoblasts and chondrocytes. In Part 4, sulfuretin inhibited the differentiation of mesenchymal stem cells to adipocytes, and it was confirmed that sulfuretin affected the differentiation of osteoblasts and chondrocytes. Even though recent studies have suggested that sulfuretin increases osteoblast differentiation, its mechanisms have not been studied. Therefore, in this study, I tried to identify the genes that changed the most significantly through RNA sequencing after sulfuretin treatment in osteoblasts. Experiments confirmed that all the features of the genes increased by sulfuretin are related to Nrf2. This means that sulfuretin has a function related to bone formation through Nrf2. As a result, this study was found that sulfuretin has an anti-obesity effect and bone formation through Atf3-Nrf2 axis. Although the movement to treat obesity and metabolic syndrome through natural products is active, it should be applied to humans to cure diseases without side effects.

Effects of arginase inhibition on hepatic metabolic abnormalities and endothelial dysfunction in obesity

문지영 Korea University 2017 국내박사

Obesity is a serious health problem worldwide and is involved in disturbed lipid profiles and endothelial dysfunction contributable to impaired release of nitric oxide (NO). Increased activity of arginase which competes with endothelial NO synthase (eNOS) for L-arginine is found in obesity, reduces NO production, and thereby has been implicated in the endothelial dysfunction in various chronic diseases. The aim of this study was to examine whether the arginase inhibition by Nω-hydroxy-nor-L-arginine (nor-NOHA) influences hepatic metabolic pathways and whole body adiposity and restores endothelial function in diet induced obesity. After obesity induction by the high fat diet (HFD) for 7 weeks, the animals were placed on either HFD only or HFD with nor-NOHA (40mg kg-1) for additional 5 weeks. Body weight, liver and visceral fat weights, biochemical measurements and mRNA expression of hepatic genes involved in lipid metabolism and mitochondrial function were evaluated. Effects of nor-NOHA treatment on lipid accumulation were also evaluated in oleic acid induced hepatic steatosis in vitro. Oral supplementation of arginase inhibitor, nor-NOHA, significantly prevented high fat diet-induced increment of body weight, liver and visceral fat tissue weight and ameliorated abnormal lipid profiles. It was also observed that nor-NOHA treatment reduced lipid accumulation in oleic acid induced hepatic steatosis in vitro. Arginase inhibition increased hepatic NO in mice fed HFD and HepG2 cells. Elevated mRNA expressions of hepatic peroxisome proliferator-activated receptors (PPAR)γ-2, adipose differentiation-related protein (ADRP) and stearoyl-Coenzyme A desaturase (SCD)-1 in HFD were reversed by arginase inhibition. Expressions of phosphorylated 5' AMPK-activated protein kinase (p-AMPK)α were increased by arginase inhibition in the liver of animals and HepG2 cells. Furthermore, arginase and eNOS expression and nitrite level in aorta and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in plasma were measured. Arginase 1 expression was significantly lower in the aorta of C57BL/6J mice fed HFD supplemented with nor-NOHA (40 mg·kg-1/day) than in mice fed HFD without nor-NOHA. Arginase inhibition led to considerable increases in eNOS expression and NO levels and significant decreases in the levels of circulating ICAM-1. These findings were further confirmed by the results of siRNA-mediated knockdown of Arg in human umbilical vein endothelial cells. Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity possibly through the increment of hepatic NO production through which metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function were activated. Also, arginase inhibition can help restore dysregulated endothelial function by increasing the eNOS-dependent NO production in the endothelium, indicating that arginase could be a therapeutic target for correcting obesity-induced vascular endothelial dysfunction.

골관절염 노인에서 근감소성 비만과 슬관절전치환술 후 하지기능과의 관계

문수희 제주대학교 대학원 2021 국내석사

This retrospective study aimed to investigate the prevalence of obesity,sarcopenia, and sarcopenic obesity in elderly patients with osteoarthritis, todetermine the relationship between obesity, sarcopenia, sarcopenic obesity, andlower limb function in these patients after total knee arthroplasty, and toprovide basic data for the development of nursing intervention for therehabilitation of lower limb function in the elderly who had undergone totalknee arthroplasty.This study analyzed the data obtained from the medical records of 986patients who underwent total knee arthroplasty and rehabilitation treatmentfor knee osteoarthritis in a university hospital with >600 beds between June2014 and December 2019. We excluded 329 patients who underwent total kneearthroplasty on both knees at the same time and 397 patients who were notevaluated before or after surgery. Altogether, the medical records of 260patients were reviewed for data analysisThe collected data were analyzed using the SPSS 23.0 program. Weperformed χ2-test and covariance analysis (ANCOVA) to examine thedifferences in obesity, sarcopenia, sarcopenic obesity, and lower limb functionafter total knee arthroplasty. Analysis of covariance (ANCOVA) was used toexamine the relationship between obesity, sarcopenia, sarcopenic obesity, andlower limb function after total knee arthroplasty. Post-test was used formultiple comparisons using the Bonferroni correction.The results of this study are as follows1) The patients’ average age was 72.7(±4.59) years, and most of the patientswere female(n=225, 86.5%). The average Number of diagnosed diseases was4.18(±1.76), and the number of drugs during hospitalization was 8.00(±2.98),with 87.3% of the patients taking ≥5 drugs per day.2) The prevalence of obesity was 51.2%, with 23.1% of the patients beingoverweight and 11.2% having extremity obesity. The prevalence of sarcopeniaand sarcopenic obesity was 15.4% and 6.2%.3) When comparing the prevalence of obesity, sarcopenia, and sarcopenicobesity characteristics of the participants and disease-related characteristics,type of insurance(χ2=8.39, p=.020) and education(χ2=17.57, p=.007) werestatistically significantly different among patients classified according to thedegree of obesity. age(χ2=9.97, p=.002), gender(χ2=4.88, p=.027), Cohabitant(χ2=7.57, p=.006), type of insurance(χ2=6.68, p=.023), and education(χ2=17.46,p<.001) were significantly different between patients with and withoutsarcopenia. Age(χ2=5.87, p=.015) and education(χ2=15.31, p<.001) weresignificantly different between patients with and without sarcopenic obesity.4) When comparing the lower limb function after total knee arthroplastyaccording to characteristics of the participants among their disease-relatedcharacteristics, the flexion angle was statistically significantly different amongpatients classified according to the number of drugs(F=4.47, p=.004) duringhospitalization. isometric knee flexor and extensor strength was significantlydifferent among patients stratified by gender(F=11.05, p=.001; F=10.54, p=.001)and job(F=9.56, p=.002; F=11.65, p=.001). TUG was statistically significantlydifferent among patients stratified by age(F=4.66, p=.032), education(F=7.15,p=.001), Kellgren Lawrence grade(F=7.19, p=.008), and Number of paindrugs(F=4.51, p=.035) during hospitalization. The time to stairs ascending aftertotal knee arthroplasty was statistically significantly different amongcharacteristics of the participants, job(F=8.55, p=.004), type of insurance(F=4.92,p=.027) and education(F=5.14, p=.007). as well as according to theirdisease-related characteristics, Kellgren Lawrence grade(F=5.22, p=.023) andNumber of diagnosed diseases(F=2.80, p=.041). The time to stairs descendingafter total knee arthroplasty was significantly different among characteristicsof the participants age(F=4.65, p=.032), job(F=8.75, p=.003), education(F=5.47,p=.005), Kellgren Lawrence grade(F=6.95, p=.009), Number of diagnoseddiseases(F=3.75, p=.012), and number of drugs(F=3.15, p=.026) duringhospitalization.There was a statistically significant difference 6MWT before total kneearthroplasty among characteristics of the participants gender(F=10.14, p=.002),job(F=4.89, p=.028), education(F=7.32, p=.001), and among disease-relatedcharacteristics number of diagnosed diseases(F=4.44, p=.005). The gait speed wasstatistically significantly different among characteristics of the participantsaccording to gender(F=4.46, p=.036), job(F=7.78, p=.006), and education(F=5.40,p=.005). There was no statistically significant difference in the K-WOMACamong characteristics of the participants and disease-related characteristics.There was a significant difference in the pain score among of the participantsdisease-related characteristics according to the number of drugs(F=3.44,p=.017) during hospitalization.5) Among the lower limb functions after total knee arthroplasty Knee JointRange of Motion extension angle(F=4.50, p=.004), stairs ascending(F=2.73,p=.045) and stairs descending(F=2.74, p=.044), 6MWT(F=5.02, p=.002) werestatistically significantly different according to the degree of obesity.6) Among the lower limb functions after total knee arthroplasty Knee JointRange of Motion flexion angle(F=5.143, p=.024), isometric knee extensorstrength(F=4.522, p=.034), and stairs descending(F=6.089, p=.014) werestatistically significantly different between patients with and withoutsarcopenia.7) Among the lower limb functions after total knee arthroplasty, isometricknee flexor strength(F=3.97, p=.047), TUG(F=5.83, p=.016), stairsascending(F=6.98, p=.009) and stairs descending(F=8.96, p=.003) werestatistically significantly different between patients with and withoutsarcopenic obesityIn summary, the prevalence of obesity, sarcopenia, and sarcopenic obesitywas high in women and elderly patients. obesity, sarcopenia, and sarcopeniawere all identified as variables that negatively affect the lower limb functionof elderly patients with osteoarthritis who had undergone total kneearthroplasty. For the elderly with obesity, sarcopenia, or sarcopenic obesity,the risk of complications after total knee arthroplasty is high, and there maybe a high risk of physical function limitations and falling, along with delayedrecovery of lower limb function. Thus, comprehensive assessment andmanagement, including evaluation of risk factors for obesity, sarcopenia, andsarcopenic obesity, should be considered in elderly patients with osteoarthritiswho are scheduled to undergo total knee arthroplasty. In addition, to reducethe risk of complications after total knee arthroplasty and to promote therecovery of lower limb function in elderly patients with obesity, sarcopenia,and sarcopenic obesity, it is necessary to provide long-term comprehensiveexercise interventions pre operatively until 1 year postoperatively.

중장년층의 비만도 측정에서 체질량지수, 이중에너지흡수계측법, 생체전기저항분석법의 상호비교

안혜란 전남대학교 대학원 2008 국내석사

배경 : 체질량지수(Body Mass Index, BMI)는 체격에 의한 비만진단 기준으로 가장 널리 사용되는 비만지표로서 일반적으로 체지방률을 잘 반영하는 것으로 알려져 있으며 성별, 연령과 관계없이 사용되고 있으나 인종, 지역, 성별의 영향을 받는다는 한계점을 가진다. 체지방에 의한 비만진단 기준으로 체지방을 간접 측정하는 방법 중 하나인 이중에너지흡수계측법(Dual Energy X-ray Absorptiometry, DXA)은 검사의 정확성이 높아 최근 체지방 분석의 기준으로 많이 사용되고 있으나 고가의 비용이 필요하고 측정시간이 오래 걸려 역학연구에서는 실제적으로 사용이 어려운 문제점을 가지고 있다. 반면 생체전기저항분석법(Bioelectrical Impedance Analysis, BIA)은 단시간에 쉽게 체지방량을 측정할 수 있는 체성분 분석법으로 경제적이고 운반이 용이하여 현재 임상 및 공중 보건분야에서 널리 사용하고 있다. 본 연구에서는 지역사회 인구를 대상으로 DXA와 BIA를 사용하여 체지방률을 동시에 측정하고, BMI, DXA, BIA의 관계를 살펴보고자 하였다. 연구방법 : 연구 대상자는 2007년 5월부터 7월까지 광주시 1개 보건소에서 만성 질환 건강검진을 받은 50세 이상 성인 남녀 총 1,681명(남성 568명, 여성 1,113명)을 대상으로 하였다. 신장과 체중을 측정하여 BMI를 계산하였고 체성분 분석은 이중에너지흡수계측법(DXA)과 생체전기저항분석법(BIA)으로 시행하였으며, 각 비만진단 기준에 따른 비만관련 심혈관질환 위험인자의 분포를 파악하였다. 모든 분석은 성별에 따라 연령을 층화하여 50대, 60대 70대 이상의 연령군으로 나누어 분석하였으며, BMI, DXA, BIA의 회귀분석을 시행하고 BMI를 기준으로 DXA와 BIA에 의한 비만도 측정의 일치도를 구하였으며, BMI의 비만진단 기준에 해당되는 DXA와 BIA의 체지방률을 알아보기 위하여 ROC 분석을 시행하였다. 특히 BIA의 경우 DXA와 체지방 측정치간의 차이를 보기 위해 BIA와 DXA의 비로 BIA-DXA Index(BDI)를 구하여 성별에 따라 연령 및 BMI와의 관계를 분석하였다. 연구결과 : BMI에 의한 비만도가 증가함에 따라 남녀 모두 심혈관질환 위험요인 유병률이 유의하게 증가하였고 특히 남성에서 더 높게 나타났다. DXA와 BIA에 의한 비만도와 심혈관질환 위험요인과의 관계는 여성보다는 남성에서 보다 유의한 증가를 보였다. BMI와 DXA로 측정된 체지방률간의 관계는 남녀 각각 r=0.710, r=0.761이었으며 DXA 및 BIA로 측정된 체지방률간의 관계는 남녀 각각 r=0.862, r=0.883으로 나타나 BMI, DXA, BIA는 상호간에 모두 높은 상관관계를 보였으나 비만도 판정에서 큰 차이를 보였으며 BMI를 기준으로 하여 체지방률이 DXA는 과소 측정되고 BIA는 과대 측정되었다. BDI는 연령이 증가할수록, BMI가 낮을수록 더 크게 나타났고 특히 70대 이상의 남성에서 74.45%로 가장 크게 나타났다. 결론 : BMI에 따른 비만도와 심혈관계질환 위험요인의 관계는 유의한 연관성이 있었다. BMI, DXA, BIA에 의한 비만도 판정은 서로 간에 큰 차이를 보였고, 특히 70세 이상의 BMI가 낮은 노년층에서 BDI가 높게 나타나 체지방률 측정에 의한 비만도 판정은 신뢰도가 낮았다. 향후 연령, 성별 등 각종 요인을 감안한 보다 정확한 비만도 판정기준이 제시되어야 할 것으로 생각된다. Background : Body mass index (BMI) is the method commonly used to diagnose obesity. Dual-energy x-ray absorptiometry (DXA) represents one of the latest technologies for high-precision body composition estimation while Bioelectrical impedance analysis (BIA) is widely used in body fat content assessment because this method is suitable for field studies. The objective of this study was to examined the relationships between obesity indices and obesity-related cardiovascular risk factors and to evaluated the relative validity and accuracy of the BMI, DXA and BIA for obesity in Korean elderly people. Methods : The study subjects were 1,681 residents (568 male and 1,113 female) of Dong-gu, Gwang-ju aged between 50-90yrs. BMI, DXA and BIA were measured for each subjects. The cut-off values for obesity were 25 for BMI in both sex, 25%(male) and 30%(female) body fat for DXA and BIA. The difference of DXA and BIA was measured by the excess ratio of BIA to DXA (BIA-DXA Index, BDI). Results : The relationships between obesity indices and cardiovascular risk factors were positive in both sex, especially in male. Although the BMI, DXA and BIA showed the linear correlation among the indices in both sex, the determination of obesity was greatly varied by the methods of measurement. While DXA was underestimated percentage of body fat, BIA was overestimated it compared with BMI. The difference between percentage of body fat by DXA and BIA was greater in older male(≥70yrs) with lower BMI. Conclusions : This study suggests that DXA and BIA were showed significant discrepancy in obesity determination. Further evaluation of obesity determination process would be recommended especially in the aged people.

Population Proteomics: Qualitative and Quantitative Analysis of Protein Markers for Obesity from Plasma Proteome

최진녕 건국대학교 대학원 2013 국내석사

비만은 지난 10년간 전세계적인 문제가 되었다. 비만은 그 자체로도 문제가 되지만, 다양한 질병을 유발하고 건강 상태를 악화시키기 때문에 위험도가 큰 질환이다. 전세계적 전염병이자 다양한 대사질환과 연관된 비만의 주원인으로 건강하지 못한 식습관과 유전적 요인을 꼽는다. 본 연구에서는 유전적 요인을 배제하고 비만과 비만에 의한 다양한 질병들의 위험을 나타낼 수 있는 마커 단백질을 찾아보고자 한다. 본 연구는, LC-MS/MS 분석법을 이용하여 건강한 마른 사람들과 건강한 비만인 사람들 사이의 혈장 단백질을 비교하고, 비만을 표지하는 단백질을 찾는 것이 그 목표이다. MS/MS 스펙트럼을 바탕으로, 99% 이상의 신뢰도를 보이고 2개 이상의 unique peptide를 갖는 412개의 단백질을 동정했다. 이 단백질들 가운데, 반정량분석법을 통해 발현 양의 차이를 보이는 단백질(DEPs)을 선택하였다. 각 DEPs 단백질들은 질량분석기를 기반으로 한 정량 분석, Multiple reaction monitoring 분석을 통해 확인하였다. 또한 비만에 유용한 후보 단백질을 검증하기 위해 paired t-test 통게적 분석을 수행하였다. 후보 단백질 가운데 6개 단백질은 비만 마커 단백질로의 가능성을 보였다. Obesity has in the last decade become a global problem. Obesity is a concern because of its implications for the health of an individual as it increases the risk of many diseases and heath conditions. Unhealthy diet and obesogenic lifestyle along with genetic susceptibility are the main causes of the global epidemic of obesity and related metabolic diseases. In this study, we focused on some factors that could affect to be obesity besides genetic factors and considering the risk of associated disease we need biomarkers which may represent increased risk for obesity-related diseases. This study used LC-MS/MS-based approach in obesity research to identify proteins in plasma that discriminate healthy lean from healthy overweight/obese groups and to quantify of several candidate proteins that could be biomarkers which are likely implicated in obesity. Based on MS/MS spectra of plasma proteins from lean and obesity group, we identified a total of 412 proteins with greater than 99% possibility and with at least 2 unique peptides. Among these proteins, we selected the differentially expressed proteins (DEPs), via semi-quantitative analysis of comparing the spectral counts of the identified. These DEPs were successfully verified using a MS-based quantitative assay, multiple reactions monitoring (MRM) analysis. Additionally, we performed a statistical analysis of paired t-test to validate the useful candidate proteins for obesity. Among the candidate proteins, 6 proteins were shown the possibility as marker proteins for obesity.

Association of components of metabolic diseases and obesity with single nucleotide polymorphisms of PPARG, PPARD, ADRB2, ADRB3, UCP1, UCP2, UCP3, SDC3, FABP2 in Korean children

이명원 Korea University 2016 국내박사

Obesity is a complex disorder related to numerous genetic and environmental factors. Also, considering the worldwide rise in childhood obesity, there is clearly a need for genetic studies related to childhood obesity. So we profiled numerous candidate genes in order to identify novel genetic contributors to obesity. In an effort to elucidate effects of polymorphisms of candidate genes on obesity phenotypes, we genotyped 12 single nucleotide polymorphisms (SNP) in syndecan-3 (SDC3; rs2282440), uncoupling protein 1 (UCP1; rs3811791), UCP1 (rs1800592), UCP1 (rs45539933), uncoupling protein 2 (UCP2; rs659366), UCP2 (rs660339), uncoupling protein 3 (UCP3; rs1800849), adrenergic receptor beta 2 (ADRB2; rs1042713), adrenergic receptor beta 3 (ADRB3; rs4994), peroxisome proliferator-activated receptor delta (PPARD; rs2016520), peroxisome proliferator-activated receptor gamma (PPARG; rs3856806), fatty acid-binding protein 2 (FABP2; rs1799883) among the Korean childhood population. The aim of the present study is to investigate the effects of these polymorphisms on clinical characteristics of components of metabolic syndrome (MetS). We studied 81 patients with obesity, 176 patients with over-weight, 469 non-obesity controls. The SNPs were analyzed in all subjects and we measured their body weight, body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST) and Alanine transaminase (ALT) levels, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, fasting blood glucose (FBS) and triglycerides (TG). We checked the prevalence of the SNPs and the clinical factors by genotypes in Korean children. As a result, UCP1 (rs45539933) was observed statistical significance with HDL (P = 0.049), UCP1 (rs3811787) was associated with AST level (P = 0.033). In case of ADRB2 (rs1042713), there is statistical significance with DBP (P = 0.010). FABP2 (rs1799883) genotype and SBP also statistical significance was confirmed (P = 0.023). Although the overall distribution of genotype and allele was not significantly different between the non-obese and the obese groups/overweight group, but in a separate analysis according to sex, the BMI distributions of the SDC3 genotype were significantly different in boy (P = 0.027) and in girls (P = 0.009). Also we found a gender difference in TC genotype of SDC3 (P = 0.018). And FABP2 (rs17999883) was associated with HDL-C level (P = 0.037) in boys. ADRB2 (rs1042713) was associated with FBS level (P = 0.022) in boys. ADRB3 (rs4994) was associated with TG level (P = 0.031) in boys, TC level (P = 0.007), HDL-C level (P = 0.024), LDL-C level (P = 0.034) in girls. UCP2 (rs659366) was associated with waist (P = 0.019) in boys, UCP2 (rs660339) was related with FBS level (P = 0.007) in girls. However, no substantial association was found between the PPARG (rs3856806), PPARD (rs2016520), UCP1 (rs1800592), UCP2 (rs659366), UCP2 (rs660339), UCP3 (rs1800849) polymorphisms and childhood obesity, components of MetS diseases in Korean childhood population. In conclusion, these result suggested that SDC3 (rs2282440), UCP1 (rs45539933), UCP2 (rs659366, rs660339) ADRB2 (rs1042713), ADRB3 (rs4994), FABP2 (rs1799883) are possible genetic markers for the components of MetS in Korean children. 비만의 표현형 및 대사성증후군 요인 요소들과에 있어서 강력한 후보 유전자의 다형성 영향을 밝히기 위하여 한국 소아를 대상으로 SDC3 (rs2282440), UCP1 (rs3811791), UCP1 (rs1800592), UCP1 (rs45539933), UCP2 (rs659366), UCP2 (rs660339), UCP3 (rs1800849), ADRB2 (rs1042713), ADRB3 (rs4994), PPARD (rs2016520), PPARG (rs3856806), FABP2 (rs1799883)의 단일 유전자 다형성에 대한 유전자 검사를 진행하였다. 본 연구의 목표는 소아 비만 및 대사성 증후군의 임상적 마커들과 상기 후보군 유전자들의 단일염기다형성과의 관련성에 대해 조사, 연구하는 것이다. 본 연구는 81명의 비만 환자들, 176명의 과체중 환자들, 469명의 비만하지 않은 대조군을 포함하였다. 모든 환자들과 대조군대상으로 상기 후보군 유전자들의 Single nucleotide polymorphism (SNP)을 분석하였으며, 실험군의 weight, body mass index (BMI), waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), fasting blood sugar (FBS)를 측정하였다. 그 결과 HDL-C (P = 0.049)수치와 UCP1 (rs45539933) 및 UCP1 (rs3811787)과 AST (P = 0.033)의 통계적 연관성이 관찰되었고, ADRB2 (rs1042713)의 경우 DBP 수치(P = 0.01)와의 통계적 유의성이 있었다. FABP2 (rs1799883)의 유전자형과 SBP (P = 0.023)수치에서의 통계적 유의성 또한 확인되었다. 전반적인 유전자형과 대립 유전자형에 대한 공헌도는 비만하지 않은 그룹, 비만 혹은 과체중 그룹간에 크게 다르지 않았으나, 성별에 따른 독립된 연구에서는 SDC3 유전자형의 BMI에 대한 영향이 남아에서 (P = 0.027) 그리고 여아에서 (P = 0.009)의 통계적 유의성을 보였다. 또한 SDC3 (rs2282440) TC genotype에서 성별 차이를 발견하였다 (P = 0.018). FABP2 (rs17999883)는 남아에서 HDL-C level (P = 0.037)과 그 통계적 유의성을 보였다. 또한 남아의 경우 ADRB2 (rs1042713)와 FBS (P = 0.022)수치와 통계적 유의성을 보였으며, ADRB3 (rs4994) 유전형의 경우 남아에서 TG (P = 0.031), 여아에서 TC (P = 0.007), HDL-C (P = 0.024), LDL-C (P = 0.034)수치들과의 통계적 유의성을 발견하였다. 여아에서 UCP2 (rs660339) 유전형과 FBS (P = 0.007), 남아에서 UCP2 (rs659366) 유전형과 waist (P = 0.019) 와의 통계적 유의성이 관찰되었다. 결과적으로 SDC3 (rs2282440)의 경우 소아비만과 관련이 있었으며, UCP1 (rs3811787), UCP1 (rs45539933), UCP2 (rs660339), UCP2 (rs660339), ADRB2 (rs1042713), ADRB3 (rs4994), FABP2 (rs1799883)의 경우 한국 소아에게 있어서 대사성 질환 관련 항목들과의 통계적 유의성을 확인하였다. 또한 SDC3 유전형의 경우 남녀에서 비만과의 그 영향력이 다르게 관측된 바 소아비만 예측 인자로서의 가능성이 있는 유전적 요소임을 보여준다. 그러나 한국 소아에 있어서 기존 한국 성인 대상 연구와는 다르게 PPARG (rs3856806), PPARD (rs2016520), UCP1 (rs1800592), UCP3 (rs1800849)의 유전자다형성과 대사성 질환 위험 요소 및 비만과의 그 어떠한 통계적 연관성도 발견되지 않았다.