식이유도 비만 생쥐의 체중조절시 식이제한 및 운동처치에 따른 희생양상 = Tendency of death following dietary restriction and exercise interventions for body weight control in diet-induced obese mice

국문 초록 (Abstract)

연구배경: 체중조절 관련 연구를 수행하는 과정에서 가장 보편적으로 이용되는 식이유도에 의한 비만 생쥐를 대상으로 식이와 운동프로그램에 의한 비만처치방법을 적용한 한 사례에서 안전성과 관련된 특이한 결과를 얻게 되었다.
방법: 본 연구의 대상은 4주령 된 수컷 C57/BL6 생쥐 64마리(오리엔트바이오, 한국)를 식이에 의한 비만을 유도한 후 약 50% 이상의 식이제한(DR 그룹), 유산소운동(EX 그룹), 50% 이상의 식이제한과 유산소 운동의 병행(DREX 그룹) 등과 같이 세 가지 방법을 각각 적용하여 8주간의 비만처치를 실시하였다. 식이섭취량과 체중의 변화양상은 그룹 및 시기 간의 이원반복변량분석을 적용하였으며, 상호작용효과가 나타날 경우 사후검증으로 시기별 그룹간 사후검정은 Bonferroni 테스트를 적용하였으며, 그룹별 시기간 변화는 일원변량분석 및 Contrast 분석을 적용하였다. 통계적 유의수준은 5%를 기준으로 하였다.
결과: 비만처치과정에서 DR그룹 및 DREX그룹은 식이제한에 따른 사료섭취량이 현저하게 감소하였다. 비만처치 2주부터 DR과 DREX 그룹은 9주에 이르기까지 지속적으로 체중이 감소하였으며, Control 및 EX 그룹의 체중은 비만처치 2주와 3주에서 감소하였으나 4주부터는 다시 유지 및 증가하였다. DR그룹에서는 처치 6주에 1마리, 7주에 2마리, 8주에 2마리가 각각 희생되었으며 9주후에 11마리만이 생존하였다. DREX그룹에서는 처치 6주에 2마리, 7주에 5마리, 8주에 6마리, 9주에 1마리가 각각 희생되었으며 9주후에는 2마리만이 생존하였다. 그러나 Control그룹 및 EX그룹은 희생된 생쥐가 없었다.
결론: 식이제한 및 운동처치를 통한 비만처치과정에서 나타난 생쥐들의 희생에는 과도한 식이제한으로 인한 부정적인 요소, 심장의 과도한 스트레스, 면역기능 저하 및 산화스트레스 등의 복합적인 요인들이 영향을 미친 것으로 간주된다. 따라서 비만처치과정에서는 개인의 특성을 신중하게 고려하고, 과도한 식이제한과 운동으로 인하여 나타나는 체중감소의 부정적인 영향에 대한 정확한 원인을 분석해야 한다.

다국어 초록 (Multilingual Abstract)

Background : Diet-induced obese mice were used as subjects in the course of experimental trial involving weight control. Unusual results were obtained by application of obesity treatment methods as in dietary restriction and exercise intervention.
Methods : Subjects were the male mice C57/BL6 at the age of 4 weeks (n=64, Orientbio Inc. Korea). Subjects were diet induced obese by consuming a 45% high fat diet (D12451, Research, Inc.) for 5 weeks, subjects were randomly assigned to 4 groups at the beginning of another 8 weeks. The four groups consisted of Control (no intervention), EX (exercise intervention), DR (dietary restriction) and DREX (dietary restriction and exercise intervention).
Results : In the process of obese treatments, the amount of intake was markedly reduced in DR and DREX groups. Weights of DR and DREX groups went on decreasing from the 2nd week up to the 9th week. Weights of Control and EX groups decreased from the 2nd week continuing to the 4th week. Their weight started to increase, however, from then on.. Mice in DR group died on the 6th week (n=1), the 7th week (n=2) and the 8th week (n=2), but other mice lived on until the 9th week (n=11). Mice in DREX died on the 6th week (n=2), the 7th week (n=5), the 8th week (n=6) and the 9th week (n=1), but only 2 mice remained alive on the 9th week. However, all of mice in Control and Ex groups stayed alive.
Conclusion : Mortality was noted during the course of obesity treatment in both dietary restriction group and in dietary restriction with exercise group. Taking this into consideration, excessive dietary restriction. seems to take part in negatively affecting cardiac overload, decline of immune function and increasing oxidative stress. In conclusion, not only the positive effects but also the negative side effects of weight loss, along with individual characteristics, should be taken into consideration. Further studies are needed to understand the negative effects of weight loss caused by excessive dietary restriction.

참고문헌 (Reference)

1 홍은경, "일부 도시 청소년 여학생들의 신체상에 대한 인지와 체중조절 형태" 18 (18): 714-721, 1997

2 김상만, "우리나라 비만증 환자의 치료지침" 19 (19): 332-338, 1998

3 정승교, "여중생의 체중조절 실태, 비만도 및 신체상에 관한 연구" 14 (14): 1-13, 1997

4 오현주, "서울시내 남녀 중학생의 체중조절 관심과 체위별 식행동에 관한 연구" 숙명여자대학교 1997

5 박선주, "서울 여고생의 체중조절 시도 여부에 따른 체중조절 관심도" 11 (11): 356-367, 2001

6 홍용, "레슬링 선수들의 장기간 체중감량이 혈액 성분, 면역세포 및 운동능력에 미치는 영향과 철 투여의 효과" 40 (40): 777-789, 2001

7 임인숙, "다이어트의 사회문화적 환경-여대생의 외모차별 경험과 대중매체의 몸 이미지 수용도를 중심으로-" 한국사회학회 38 (38): 165-187, 2004

8 Pamuk ER, "Weight loss and subsequent death in a cohort of U.S. adults" 119 : 744-748, 1993

9 Pamuk ER, "Weight loss and mortality in a national cohort of adults, 1971-1987" 136 (136): 686-697, 1992

10 Pi-Sunyer FX, "The role of very-low-calorie diets in obesity" 56 (56): 240-243, 1992

11 Weindruch R, "The retardation of aging in mice by dietary restriction: Longvity, cancer, immunity and lifetime energy intake" 116 : 641-654, 1986

12 Wolf AM, "The health economics of obesity and weight loss in Eating Disorders and Obesity: A Comprehensive Handbook. 2nd ed" The Guildford Press 453-459, 2002

13 Weindruch R, "The Retardation of Aging and Disease by Dietary Restriction" SpringÞeld 1988

14 Stillman IM, "The Doctor's quick weight loss diet" Dell Publishing Co 1-204, 1978

15 Isner JM, "Sudden, unexpected death in avid dieters using the liquidprotein-modified-fast diet. Observation in 17 patient and the role of the prolonged QT interval" 60 : 1401-1402, 1979

16 Sours HE, "Sudden death associated with very low calorie weight reduction regimens" 34 (34): 453-461, 1981

17 Wadden TA, "Responsible and irresponsible use of very-low-calorie diets in the treatment of obesity" 263 (263): 83-85, 1990

18 Sjostrom CJ, "Relationships between changes in body composion and changes in crdiovascular risk factors: The SOS Intervention Study" 5 (5): 519-530, 1997

19 Drenick EJ, "Prolonged starvation as treatment for severe obesity" 187 : 100-106, 1964

20 American Dietetic Association, "Position of the American Dietetic Association: weight management" 97 : 71-74, 1997

21 Kenz WL, "Oxidative stress in half and full Ironman triathletes" 39 (39): 283-288, 2007

22 Husain K, "Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart" 1578 (1578): 75-82, 2002

23 Jacob RA, "Oxidative damage and defence" 63 (63): 985-990, 1996

24 Fisher MC, "Nutrition evaluation of published weight-reduction diets" 85 : 450-454, 1985

25 St Jeor ST, "Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. Dietary protein and weight reduction: a statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association" 104 (104): 1869-1874, 2001

26 Sjostrom L, "Motality in severely obese subjects" 55 (55): 516-523, 1992

27 Foster C, "Monitoring training in athletes with reference to overtraining syndrome" 30 (30): 1164-1168, 1998

28 Hooper SL, "Markers for monitoring overtraining and recovery" 27 (27): 106-112, 1995

29 Fontana L, "Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans" 101 : 6659-6663, 2004

30 Jenkins RR, "Introduction: oxidant stress, aging, and exercise" 25 (25): 210-212, 1993

31 Institute of Medicine(IOM), "In Weighing the Option: Criteria for Evaluating Weight-management Program" National Academy press 1995

32 Nieman DC, "Immune response to heavy exertion" 82 : 1385-1394, 1997

33 Berg FM, "Health risks of weight loss, Third Edition Hettinger" Healthy Weight Journal 1995

34 Halliwell B, "Free radicals, antioxidants, and human disease: curiosity, cause, or consequence?" 344 (344): 721-724, 1994

35 Ji LL, "Exercise-induced modulation of antioxidant defense" 959 : 82-92, 2002

36 De Angelis K, "Exercise training changes autonomic cardiovascular balance in mice" 96 (96): 2174-2178, 2004

37 Kramer YR, "Effects of food restriction in military training on T-lymphocyte response" 18 : 84-90, 1997

38 Lee MI, "Change in body weight and longevity" 268 : 2045-2049, 1992

39 Alessio HM, "Cardiovascular adjusments to high- and low-intensity exercise do not regulate temporary threshold shifts" 21 (21): 163-172, 1992

40 Van Itallie TB, "Cardiac dysfunction in obese dieters: a potentially lethal complication of rapid, massive weight loss" 39 (39): 695-702, 1984

41 Higgins M, "Benefits and adverse effects of weight loss" 119 : 758-763, 1993