Abstract
Aging results in progressive decline of renal function as well as histological alterations including glomerulosclerosis and interstitial fibrosis. The objective of current study was to test the benefits of moderate swimming exercise in aged rats on renal function and structure and investigate its molecular mechanisms. Aged rats of 21-months old were given moderate swimming exercise for 12 weeks. Swimming exercise in aged rats led to reduced plasma levels of creatinine and blood urea nitrogen. Periodic acid-Schiff staining results revealed reduced renal injury scores in aged rats after swimming exercise. Swimming exercise in aged rats mitigated renal fibrosis and downregulated the mRNA expression of Acta2, Fn, Col1a, Col4a, and Tgfb1 in kidneys. Swimming exercise in aged rats attenuated lipid accumulation and reduced levels of triglyceride in kidneys. Swimming exercise in aged rats abated oxidative stress, evidenced by reduced MDA levels and increased MnSOD activities in kidneys. Swimming exercise in aged rats inhibited NF-κB activities and reduced renal expression of pro-inflammatory cytokines including MCP-1, IL-1β and IL-6. Mechanistically, swimming exercise restored mRNA and protein expression of PPAR-α in kidney of aged rats. Furthermore, swimming exercise in aged rats increased expression of PPAR-α-targeting microRNAs including miR-21 and miR-34a. Collectively, swimming exercise activated PPAR-α, which partly explained the benefits of moderate swimming exercise in aging kidneys.
Similar content being viewed by others
Data availability
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- BUN :
-
Blood urea nitrogen
- MCP-1 :
-
Macrophage chemoattractant protein 1
- MDA :
-
Malondialdehyde
- PAS :
-
Periodic acid-Schiff
- PPAR- α :
-
Peroxisome proliferator-activated receptor alpha
- qRT-PCR :
-
Quantitative real-time PCR
- ROS :
-
Reactive oxygen species
References
Wang X, Bonventre JV, Parrish AR (2014) The aging kidney: increased susceptibility to nephrotoxicity. Int J Mol Sci 15:15358–15376
Hommos MS, Glassock RJ, Rule AD (2017) Structural and functional changes in human kidneys with healthy aging. J Am Soc Nephrol 28:2838–2844
Fang Y, Gong AY, Haller ST, Dworkin LD, Liu Z, Gong R (2020) The ageing kidney: molecular mechanisms and clinical implications. Ageing Res Rev 63:101151
Chen YY, Yu XY, Chen L, Vaziri ND, Ma SC, Zhao YY (2019) Redox signaling in aging kidney and opportunity for therapeutic intervention through natural products. Free Radic Biol Med 141:141–149
Ebert T, Pawelzik SC, Witasp A, Arefin S, Hobson S, Kublickiene K, Shiels PG, Bäck M, Stenvinkel P (2020) Inflammation and premature ageing in chronic kidney disease. Toxins (Basel) 12:227
Eum JY, Lee JC, Yi SS, Kim IY, Seong JK, Moon MH (2020) Aging-related lipidomic changes in mouse serum, kidney, and heart by nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 1618:460849
Zelle DM, Klaassen G, van Adrichem E, Bakker SJ, Corpeleijn E, Navis G (2017) Physical inactivity: a risk factor and target for intervention in renal care. Nat Rev Nephrol 13:152–168
Chen IR, Wang SM, Liang CC, Kuo HL, Chang CT, Liu JH, Lin HH, Wang IK, Yang YF, Chou CY, Huang CC (2014) Association of walking with survival and RRT among patients with CKD stages 3–5. Clin J Am Soc Nephrol 9:1183–1189
Kirkman DL, Ramick MG, Muth BJ, Stock JM, Townsend RR, Edwards DG (2021) A randomized trial of aerobic exercise in chronic kidney disease: evidence for blunted cardiopulmonary adaptations. Ann Phys Rehabil Med 64:101469
Galloza J, Castillo B, Micheo W (2017) Benefits of exercise in the older population. Phys Med Rehabil Clin N Am 28:659–669
Salem HR, Faried MA (2021) Treadmill exercise training ameliorates functional and structural age-associated kidney changes in male albino rats. Sci World J 2021:1393372
Bao C, Yang Z, Li Q, Cai Q, Li H, Shu B (2020) Aerobic endurance exercise ameliorates renal vascular sclerosis in aged mice by regulating PI3K/AKT/mTOR signaling pathway. DNA Cell Biol 39:310–320
Bao C, Yang Z, Cai Q, Li Q, Li H, Shu B (2019) Incremental load training improves renal fibrosis by regulating the TGF-β1/TAK1/MKK3/p38MAPK signaling pathway and inducing the activation of autophagy in aged mice. Int J Mol Med 44:1677–1686
Wang YX (2010) PPARs: diverse regulators in energy metabolism and metabolic diseases. Cell Res 20:124–137
Li S, Nagothu KK, Desai V, Lee T, Branham W, Moland C, Megyesi JK, Crew MD, Portilla D (2009) Transgenic expression of proximal tubule peroxisome proliferator-activated receptor-alpha in mice confers protection during acute kidney injury. Kidney Int 76:1049–1062
Chung KW, Lee EK, Lee MK, Oh GT, Yu BP, Chung HY (2018) Impairment of PPARα and the fatty acid oxidation pathway aggravates renal fibrosis during aging. J Am Soc Nephrol 29:1223–1237
Diniz TA, de Lima Junior EA, Teixeira AA, Biondo LA, da Rocha LAF, Valadão IC, Silveira LS, Cabral-Santos C, de Souza CO, Rosa Neto JC (2021) Aerobic training improves NAFLD markers and insulin resistance through AMPK-PPAR-α signaling in obese mice. Life Sci 266:118868
Zhang S, Liu Y, Li Q, Dong X, Hu H, Hu R, Ye H, Wu Y, Hu R, Li Y (2011) Exercise improved rat metabolism by raising PPAR-α. Int J Sports Med 32:568–573
Kimura K, Tojo A, Matsuoka H, Sugimoto T (1991) Renal arteriolar diameters in spontaneously hypertensive rats. Vasc Cast Study Hypertens 18(1):101–110
Simon N, Hertig A (2015) Alteration of fatty acid oxidation in tubular epithelial cells: from acute kidney injury to renal fibrogenesis. Front Med (Lausanne) 2:52
Chung KW, Ha S, Kim SM, Kim DH, An HJ, Lee EK, Moon HR, Chung HY (2020) PPARα/β activation alleviates age-associated renal fibrosis in sprague dawley rats. J Gerontol A 75:452–458
Kitada M, Xu J, Ogura Y, Monno I, Koya D (2020) Manganese superoxide dismutase dysfunction and the pathogenesis of kidney disease. Front Physiol 11:755
Wang Y, Branicky R, Noë A, Hekimi S (2018) Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol 217:1915–1928
Guellich A, Damy T, Conti M, Claes V, Samuel JL, Pineau T, Lecarpentier Y, Coirault C (2013) Tempol prevents cardiac oxidative damage and left ventricular dysfunction in the PPAR-α KO mouse. Am J Physiol Heart Circ Physiol 304:H1505-1512
Lu Z, Xu Y, Song Y, Bíró I, Gu Y (2021) A mixed comparisons of different intensities and types of physical exercise in patients with diseases related to oxidative stress: a systematic review and network meta-analysis. Front Physiol 12:700055
Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY (2007) Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev 21:3244–3257
Amaral LSB, Souza CS, Volpini RA, Shimizu MHM, de Bragança AC, Canale D, Seguro AC, Coimbra TM, de Magalhães ACM, Soares TJ (2018) Previous exercise training reduces markers of renal oxidative stress and inflammation in streptozotocin-induced diabetic female rats. J Diabetes Res 2018:6170352
Bar-Shai M, Carmeli E, Reznick AZ (2005) The role of NF-kappaB in protein breakdown in immobilization, aging, and exercise: from basic processes to promotion of health. Ann N Y Acad Sci 1057:431–447
Huang D, Zhao Q, Liu H, Guo Y, Xu H (2016) PPAR-α agonist WY-14643 inhibits LPS-induced inflammation in synovial fibroblasts via NF-kB pathway. J Mol Neurosci 59:544–553
Lyu H, Li X, Wu Q, Hao L (2019) Overexpression of microRNA-21 mediates Ang II-induced renal fibrosis by activating the TGF-β1/Smad3 pathway via suppressing PPARα. J Pharmacol Sci 141:70–78
Ding J, Li M, Wan X, Jin X, Chen S, Yu C, Li Y (2015) Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease. Sci Rep 5:13729
Funding
This work was supported by grants from the National Natural Science Foundation of China (81971017 to Yongsheng Yu).
Author information
Authors and Affiliations
Contributions
Conception and design of the experiments: HXZ, ZZ, HDZ. Collection, analysis and interpretation of data: HXZ, ZZ, FH, QFW, YSY, HDZ. Drafting the article: HDZ.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Conflict of interest
The authors declare that we have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zhao, HX., Zhang, Z., Hu, F. et al. Swimming exercise activates peroxisome proliferator-activated receptor-alpha and mitigates age-related renal fibrosis in rats. Mol Cell Biochem 478, 1109–1116 (2023). https://doi.org/10.1007/s11010-022-04581-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-022-04581-3