트레드밀 운동이 고지방 식이 유도 비만 쥐의 골격근 인슐린 신호 경로에 미치는 영향
The Effects of Regular Treadmill Exercise on Skeletal Muscle Insulin Signaling Pathway in High Fat Diet Induced Obesity Rats
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
이 연구는 고지방식이 유발 비만 쥐의 8주간 규칙적인 트레드밀 운동이 인슐린 신호 전달 경로인 IRS-1/PI3K/Akt 단백질 수준과 mTOR 경로인 mTOR/mTORC1/S6K1의 변화를 살펴보기 위하여 실시하였다. 실험동물은 4주령 sprague-dawley rat 수컷 24마리를 1주간의 적응기간을 둔 뒤, 15주간 고지방식이로 비만을 유도하였다. 실험 동물은 고지방식이군(OD, n=8), 고지방식이 훈련군(ODT, n=8), 정상식이군(ND, n=8)으로 분류하였다. 트레드밀 운동은 1~4주는 주 5회 40분간 실시하였으며, 5~8주는 주5회 60분간 실시하였다. 그 결과 IRS-1과 PI3K는 OD군이 ND와 ODT군에 비해 유의하게 낮게 나타났다(p<0.05). 그리고 mTOR와 S6K1은 OD군이 ND와 ODT군에 비해 유의한 차이가 나타났다(p<0.05). 따라서 고지방식이 비만 유발 쥐의 8주간 규칙적인 트레드밀 운동은 골격근의 인슐린 신호 경로인 IRS-1과 PI3K 단백질 수준 향상에 긍정적 영향을 주며, 또한 mTOR 경로에서 S6K1을 개선시키는 것으로 나타나, 인슐린 신호경로와 S6K1의 변화를 통해 인슐린 민감성의 향상을 가져온 것으로 사료된다.
Abstract
The purpose of the study is to investigate how regular treadmill exercise for 8 weeks affects on expression of insulin pathway (IRS-1/PI3K/Akt) which is crucial signaling pathway to modulate insulin homeostasis on skeletal muscle for obese rats induced by high fat diet for 14 weeks and what is the relation between insulin pathway and mTORC1-S6K1 (mTOR pathway) which controls insulin pathway. The subject of this study was 24 white male rats of Sprague-dawley and we induced them to be obesity by diet for 14 weeks with water after the environmental adaptation for a week. Animals were divided three groups which are obesity diet group (OD, n=8), obesity diet training (ODT, n=8) and normal diet group (ND, n=8). They performed treadmill exercise for 40 minute 5 times a week for 1 to 4 weeks. For 5 to 8 weeks, treadmill exercise was performed for 60 minute 5 times a week. As a result, IRS-1 and PI3K were significantly decreased in OD group compared with ND group and significantly increased in ODT group compared with OD group (p<0.05). Although p-Akt was not significantly change, it tended to support previous studies (p<0.05). Also, mTORC1 was not significantly changed among groups. But S6K1 was significantly decreased in OD group compared with ND group and increased in ODT group compared with OD group. Therefore, we concluded that regular treadmill exercise for 8 weeks increased IRS-1 and PI3K protein levels affected on positive insulin signaling pathway. Furthermore, not overexpression of mTORC1-S6K1 but leading the change of S6K1 caused differentiation of insulin signaling steps according to muscular fiber.
참고문헌 (26)
- 박수현, "12주 걷기 운동 프로그램의 운동강도가 비만여성의 신체조성, 복부지방, 심폐체력에 미치는 영향", 운동과학, 16(1), pp.1~10 (2007), 한국운동생리학회
- Benziane, B., "Divergent cell signaling after short‐term intensified endurance training in human skeletal muscle", Am. J. Physiol. Endocrinol. Metab, 295, pp.1427~1438 (2008)
- Bodine, S. C., "Akt", mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo, 2001, pp.3, 1014~1019
- 이기업, "Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats", AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 278(6), pp.977~984, AMER PHYSIOLOGICAL SOC
- Coffey, V. G., "The molecular bases of training adaptation", Sports Med, 37, pp.737~763 (2007)
- Corcoran, M. P., "Skeletal muscle lipid deposition and insulin resistance: Effect of dietary fatty acids and exercise", Am. J. Clin. Nutr, 85, pp.662~677 (2007)
- Hay, N., "Upstream and downstream of mTOR", Genes. Dev, 18, pp.1926~1945 (2004)
- Houmard, J. A., "Effect of shortterm exercise training on insulin stimulated PI3-kinase activity in human skeletal muscle", Am. J. Physiol, 277, pp.1055~1060 (1999)
- Isotani, S., "Immunopurified mammalian target of rapamycin phosphorylates and activates p70S6 kinase alpha in vitro", J. Biol. Chem, 274, pp.34493~34498 (1999)
- Kirwan, J. P., "Regular exercise enhances insulin activation of IRS‐1 associated PI3‐kinase in human skeletal muscle", J. Appl. Physiol, 88, pp.797~803 (2000)
- Krebs, M., "The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man", Diabetes, 56, pp.1600~1607 (2007)
- Leger, B., "Akt signaling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy", J. Physiol, 576, pp.923~933 (2006)
- Liao, B., "Exercise improves skeletal muscle insulin resistance without reduced basal mTOR", S6K1 signaling in rats fed a high‐fat diet, 2011, pp.111, 2743~2752
- Miyazaki, M., "Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals", J. Appl. Physiol, 106, pp.1519~1529 (2009)
- Medeiros, C., "Exercise reduces insulin resistance and upregulates the mTOR", p70S6k pathway in cardiac muscle of diet‐induced obesity rats, 2011, pp.226, 666~674
- Patti, M. E., "Bidirectional modulation of insulin action by amino acids", J. Clin. Invest, 101, pp.1519~1529 (1998)
- Powers, T., "Cell growth control: mTOR takes on fat", Mol. Cell, 31, pp.775~776 (2008)
- Rasmussen, B. B., "The balancing act between the cellular processes of protein synthesis and breakdown: Exercise as a model to understand the molecular mechanisms regulating muscle mass", J. Appl. Physiol, 106, pp.1365~1366 (2009)
- Rivas, D. A., "mTOR function in skeletal muscle: A focal point for overnutrition and exercise", Appl. Physiol. Nutr Metab, 34, pp.807~816 (2009)
- Sakamoto, K., "Role of Akt 2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle", Am. J. Physiol. Endocrinol. Metab, 291, pp.1031~1037 (2006)
- Serrano, A. L., "Calcineurin controls nerve activity dependent specification of slow skeletal muscle fibers but not muscle growth", Proc. Natl. Acad. Sci. USA, 98, pp.13108~13113 (2001)
- Sim, Y. J., "Effect of postnatal treadmill exercise on c‐Fos expression in the hippocampus of rat pups born from the alcoholintoxicated mothers", Brain Dev, 30, pp.118~125 (2008)
- Tremblay, F., "Modulation of insulin action by dietary proteins and amino acids: Role of the mammalian target of rapamycin nutrient sensing pathway", Curr. Opin. Clin. Nutr. Care, 8, pp.457~462 (2005)
- Tremblay, F., "Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient-and obesity- induced insulin resistance", Proc. Natl. Acad. Sci USA, 104, pp.14056~14061 (2007)
- Tremblay, F., "Amino acid and insulin signaling via the mTOR", p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells, 2001, pp.276, 38052~38060
- Um, S. H., "Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1", Cell Metab, 3, pp.393~402 (2006)
