Swimming improves high-fat induced insulin resistance by regulating lipid and energy metabolism and the insulin pathway in rats

Song,An; Wang,Chao; Ren,Luping; Zhao,Jiajun

doi:10.3892/ijmm.2014.1738

Swimming improves high-fat induced insulin resistance by regulating lipid and energy metabolism and the insulin pathway in rats

Authors:
- An Song
- Chao Wang
- Luping Ren
- Jiajun Zhao
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Affiliations: Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Endocrinology, General Hospital of Hebei, Shijiazhuang, Hebei 050051, P.R. China
Published online on: April 9, 2014 https://doi.org/10.3892/ijmm.2014.1738
Pages: 1671-1679

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Abstract

In this study, we aimed to determine the preventive and therapeutic effects of swimming on insulin resistance in high-fat-fed rats. Sprague-Dawley rats were divided into 4 groups and fed for 8 weeks as follows: i) the control (Con) group fed a control diet; ii) the high-fat (HF) group fed a high-fat diet; iii) the treatment (ST) group fed a high-fat diet and trained with swimming from the 4th week; and iv) the prevention (SP) group fed a high-fat diet and trained with swimming from the 1st week of the experiment. A hyperinsulinemic‑euglycemic clamp was used to evaluate the insulin sensitivity of the rats. The ultrastructure of the liver cells was observed by electron microscopy. Hepatic lipid accumulation was observed by Oil Red O staining. Quantitative RT-PCR and western blot analysis were performed to detect the expression of proteins related to lipid metabolism, energy metabolism and insulin signaling transduction. After 8 weeks of feeding, compared with the Con group, the glucose infusion rate (GIR) was significantly decreased; a significant lipid accumulation was observed in the liver, while the ultrastructure of the liver cells was damaged in the HF group. Proteins related to lipid metabolism in the liver and skeletal muscle, including FAT and FABP were upregulated, while CPT1 and PPAR levels were downregulated in the HF group. The levels of the energy-metabolism-related molecules, AMPKα2, PGC1α, PGC1β and MFN2 were downregulated in skeletal muscle in the HF group. The expression levels of insulin signaling transduction molecules, INSR, IRS1, PI3K/p85, AKT2 and GLUT4, as well as the phosphorylation levels of INSR, IRS1, PI3K/p85 and AKT2 were lower in skeletal muscles in the HF rats. Compared with HF group, the GIR levels were significantly increased in the ST and SP groups. Lipid accumulation and damage to the ultrastructure of the liver cells were improved in both groups. The expression of molecules related to lipid metabolism in the liver and skeletal muscle, energy metabolism in skeletal muscle and insulin signaling transduction were all markedly upregulated. In conclusion, swimming can effectively improve insulin sensitivity and even prevent insulin resistance by affecting the expression of proteins related to lipid metabolism, energy metabolism and insulin signaling transduction in rats fed a high-fat diet.

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1	Karpe F, Dickmann JR and Frayn KN: Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes. 60:2441–2449. 2011. View Article : Google Scholar
2	Wang ZL, Xia B, Shrestha U, et al: Correlation between adiponectin polymorphisms and non-alcoholic fatty liver disease with or without metabolic syndrome in Chinese population. J Endocrinol Invest. 31:1086–1091. 2008. View Article : Google Scholar : PubMed/NCBI
3	Chow L, From A and Seaquist E: Skeletal muscle insulin resistance: the interplay of local lipid excess and mitochondrial dysfunction. Metabolism. 59:70–85. 2010. View Article : Google Scholar : PubMed/NCBI
4	Martins AR, Nachbar RT, Gorjao R, et al: Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function. Lipids Health Dis. 11:302012. View Article : Google Scholar : PubMed/NCBI
5	Song GY, Ren LP, Chen SC, et al: Similar changes in muscle lipid metabolism are induced by chronic high-fructose feeding and high-fat feeding in C57BL/J6 mice. Clin Exp Pharmacol Physiol. 39:1011–1018. 2012. View Article : Google Scholar : PubMed/NCBI
6	Iellamo F, Caminiti G, Sposato B, et al: Effect of high-intensity interval training versus moderate continuous training on 24-h blood pressure profile and insulin resistance in patients with chronic heart failure. Intern Emerg Med. Jul 16–2013.(Epub ahead of print).
7	Chowdhury KK, Legare DJ and Lautt WW: Interaction of antioxidants and exercise on insulin sensitivity in healthy and prediabetic rats. Can J Physiol Pharmacol. 91:570–577. 2013. View Article : Google Scholar : PubMed/NCBI
8	Buettner R, Parhofer KG, Woenckhaus M, et al: Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol. 36:485–501. 2006. View Article : Google Scholar : PubMed/NCBI
9	Bray GA, Lovejoy JC, Smith SR, et al: The influence of different fats and fatty acids on obesity, insulin resistance and inflammation. J Nutr. 132:2488–2491. 2002.PubMed/NCBI
10	McGarry JD: Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes. 51:7–18. 2002. View Article : Google Scholar : PubMed/NCBI
11	Gan KX, Wang C, Chen JH, Zhu CJ and Song GY: Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of rats. World J Gastroenterol. 19:1572–1581. 2013. View Article : Google Scholar : PubMed/NCBI
12	Song GY, Gao Y, Wang C, et al: Rosiglitazone reduces fatty acid translocase and increases AMPK in skeletal muscle in aged rats: a possible mechanism to prevent high-fat-induced insulin resistance. Chin Med J (Engl). 123:2384–2391. 2010.PubMed/NCBI
13	Kong D, Song G, Wang C, et al: Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of highfat dietfed rats through AMP activated protein kinase signaling. Mol Med Rep. 8:205–210. 2013.PubMed/NCBI
14	Shulman GI: Cellular mechanisms of insulin resistance. J Clin Invest. 106:171–176. 2000. View Article : Google Scholar : PubMed/NCBI
15	Liu L, Zhang Y, Chen N, Shi X, Tsang B and Yu YH: Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Invest. 117:1679–1689. 2007. View Article : Google Scholar : PubMed/NCBI
16	Schenk S and Horowitz JF: Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Invest. 117:1690–1698. 2007. View Article : Google Scholar : PubMed/NCBI
17	Wang C, Han M, Zhao XM and Wen JK: Kruppel-like factor 4 is required for the expression of vascular smooth muscle cell differentiation marker genes induced by all-trans retinoic acid. J Biochem. 144:313–321. 2008. View Article : Google Scholar : PubMed/NCBI
18	Goodpaster BH, Krishnaswami S, Resnick H, et al: Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care. 26:372–379. 2003. View Article : Google Scholar : PubMed/NCBI
19	Perseghin G, Scifo P, De Cobelli F, et al: Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes. 48:1600–1606. 1999. View Article : Google Scholar
20	Virkamaki A, Korsheninnikova E, Seppala-Lindroos A, et al: Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes. 50:2337–2343. 2001. View Article : Google Scholar
21	Oppert JM, Nadeau A, Tremblay A, Despres JP, Theriault G and Bouchard C: Negative energy balance with exercise in identical twins: plasma glucose and insulin responses. Am J Physiol. 272:E248–E254. 1997.PubMed/NCBI
22	Corcoran MP, Lamon-Fava S and Fielding RA: Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. Am J Clin Nutr. 85:662–677. 2007.PubMed/NCBI
23	Samuel VT, Petersen KF and Shulman GI: Lipid-induced insulin resistance: unravelling the mechanism. Lancet. 375:2267–2277. 2010. View Article : Google Scholar : PubMed/NCBI
24	Campbell SE, Tandon NN, Woldegiorgis G, Luiken JJ, Glatz JF and Bonen A: A novel function for fatty acid translocase (FAT)/CD36: involvement in long chain fatty acid transfer into the mitochondria. J Biol Chem. 279:36235–36241. 2004. View Article : Google Scholar : PubMed/NCBI
25	Sebastian D, Herrero L, Serra D, Asins G and Hegardt FG: CPT I overexpression protects L6E9 muscle cells from fatty acid-induced insulin resistance. Am J Physiol Endocrinol Metab. 292:E677–E686. 2007. View Article : Google Scholar : PubMed/NCBI
26	Smathers RL and Petersen DR: The human fatty acid-binding protein family: evolutionary divergences and functions. Hum Genomics. 5:170–191. 2011. View Article : Google Scholar : PubMed/NCBI
27	Storch J and Thumser AE: Tissue-specific functions in the fatty acid-binding protein family. J Biol Chem. 285:32679–32683. 2010. View Article : Google Scholar : PubMed/NCBI
28	Kusudo T, Kontani Y, Kataoka N, Ando F, Shimokata H and Yamashita H: Fatty acid-binding protein 3 stimulates glucose uptake by facilitating AS160 phosphorylation in mouse muscle cells. Genes Cells. 16:681–691. 2011. View Article : Google Scholar : PubMed/NCBI
29	Ruderman NB, Carling D, Prentki M and Cacicedo JM: AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 123:2764–2772. 2013. View Article : Google Scholar : PubMed/NCBI
30	Cao S, Li B, Yi X, et al: Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes. PLoS One. 7:e517092012. View Article : Google Scholar : PubMed/NCBI
31	Velkov T: Interactions between human liver fatty acid binding protein and peroxisome proliferator activated receptor selective drugs. PPAR Res. 2013:9384012013. View Article : Google Scholar
32	Kramer DK, Al-Khalili L, Guigas B, Leng Y, Garcia-Roves PM and Krook A: Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle. J Biol Chem. 282:19313–19320. 2007. View Article : Google Scholar : PubMed/NCBI
33	Liesa M, Palacin M and Zorzano A: Mitochondrial dynamics in mammalian health and disease. Physiol Rev. 89:799–845. 2009. View Article : Google Scholar : PubMed/NCBI
34	Sebastian D, Hernandez-Alvarez MI, Segales J, et al: Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci USA. 109:5523–5528. 2012. View Article : Google Scholar : PubMed/NCBI
35	Zorzano A, Liesa M and Palacin M: Mitochondrial dynamics as a bridge between mitochondrial dysfunction and insulin resistance. Arch Physiol Biochem. 115:1–12. 2009. View Article : Google Scholar : PubMed/NCBI
36	Hernandez-Alvarez MI, Thabit H, Burns N, et al: Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1{alpha}/Mitofusin-2 regulatory pathway in response to physical activity. Diabetes Care. 33:645–651. 2010.PubMed/NCBI
37	Zorzano A, Hernandez-Alvarez MI, Palacin M and Mingrone G: Alterations in the mitochondrial regulatory pathways constituted by the nuclear co-factors PGC-1alpha or PGC-1beta and mitofusin 2 in skeletal muscle in type 2 diabetes. Biochim Biophys Acta. 1797:1028–1033. 2010. View Article : Google Scholar : PubMed/NCBI
38	Akimoto T, Pohnert SC, Li P, et al: Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. J Biol Chem. 280:19587–19593. 2005. View Article : Google Scholar : PubMed/NCBI
39	Wright DC, Geiger PC, Han DH, Jones TE and Holloszy JO: Calcium induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation. J Biol Chem. 282:18793–18799. 2007. View Article : Google Scholar
40	Egan B, Carson BP, Garcia-Roves PM, et al: Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. J Physiol. 588:1779–1790. 2010. View Article : Google Scholar
41	Saltiel AR and Kahn CR: Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 414:799–806. 2001. View Article : Google Scholar : PubMed/NCBI
42	Previs SF, Withers DJ, Ren JM, White MF and Shulman GI: Contrasting effects of IRS-1 versus IRS-2 gene disruption on carbohydrate and lipid metabolism in vivo. J Biol Chem. 275:38990–38994. 2000. View Article : Google Scholar : PubMed/NCBI
43	Osorio-Fuentealba C, Contreras-Ferrat AE, Altamirano F, et al: Electrical stimuli release ATP to increase GLUT4 translocation and glucose uptake via PI3Kgamma-Akt-AS160 in skeletal muscle cells. Diabetes. 62:1519–1526. 2013. View Article : Google Scholar : PubMed/NCBI