Journal of Traditional Chinese Medicine >
Mitochondrial dysfunction in a rat model and the related risk of metabolic disorders
Received date: 2021-09-16
Accepted date: 2021-12-11
Online published: 2023-01-10
Supported by
The Role of Mitochondrial Intergrity in the Pathophysiology of Kidney Yang Deficiency(81750110554);Central Mechanisms of Transgenerational Phenotype of Kidney Yang Deficiency in a Rat Model(2018HH0085);Molecular Mechanism of Blocking Cys259 and DD-mediated p75NTR Signaling Pathway to Delay the Progression of Alzheimer's Disease(NSFC 81971309);Mechanism Study of Cys259 Site and DD Domain of p75NTR as New Targets for the Treatment of Alzheimer's Disease(2019A1515011333);Research on Glial Connexin as a New Target for Alzheimer's Disease Treatment(F7201931620002)
OBJECTIVE: To explore whether kidney Yang deficiency (KYD) is prone to metabolic disorders may be linked to impaired mitochondrial function in thermogenesis and metabolic tissues.
METHODS: A rat model of KYD was used, which was established using Sprague Dawley rat dams with warm preference subjected to herbal treatment that can improve kidney Yang. The human relevance was confirmed by reduced serum corticosterone levels, and increased preference for warm location.
RESULTS: KYD Rats were underdeveloped. Adenosine-triphosphate (ATP) production was reduced in the brown fat, but increased in the muscle. However, oxidative phosphorylated complexes to generate ATP and mitochondrial biogenesis marker were reduced in both tissues. When the second insult of high-fat diet (HFD) was introduced, KYD rats gained less weight yet developed more severe lipid and glucose metabolic disorders. This may be driven by disregulated liver gluconeogenesis marker forkhead box protein O1 and lipid metabolic regulator cholesterol 7 alpha-hydroxylase.
CONCLUSION: KYD rats exhibited reduced mito-chondrial function in the brown fat, but were partially compensated by skeletal muscle, associated with the phenotype of warm preference and metabolic disorder, which was further exacerbated by additional HFD consumption. Future studies can focus on treatment targetting mitochondria function to reverse this phenotype.
Han LI , Xiaomin HUANG , Haiyang CAI , George HEROK , Jing HE , Yixun SU , Weihong LI , Chenju YI , Brian G OLIVER , Hui CHEN . Mitochondrial dysfunction in a rat model and the related risk of metabolic disorders[J]. Journal of Traditional Chinese Medicine, 2023 , 43(1) : 95 -104 . DOI: 10.19852/j.cnki.jtcm.20221017.001
| 1 | Chan YL, Oliver BG, Chen H. What lessons have we learnt about the impact of maternal cigarette smoking from animal models? Clin Exp Pharmacol Physiol 2020; 2: 337-44. |
| 2 | Dudkina NV, Kou?il R, Peters K, Braun H-P, Boekema EJ. Structure and function of mitochondrial supercomplexes. Biochimica et Biophysica Acta (BBA) - Bioenergetics 2010; 6-7: 664-70. |
| 3 | Chan YL, Saad S, Machaalani R, et al. Maternal cigarette smoke exposure worsens neurological outcomes in adolescent offspring with hypoxic-ischemic injury. Front Mol Neurosci 2017; 10: 306. |
| 4 | Chan YL, Saad S, Pollock C, et al. Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring. Sci Rep 2016; 6: 25881. |
| 5 | Li G, Chan YL, Sukjamnong S, et al. A mitochondrial specific antioxidant reverses metabolic dysfunction and fatty liver induced by maternal cigarette smoke in mice. Nutrients 2019; 7: 1669. |
| 6 | Li G, Chan YL, Nguyen LT, et al. Impact of maternal e-cigarette vapor exposure on renal health in the offspring. Ann NY Acad Sci 2019; 1: 65-77. |
| 7 | Zhao T, Wang H, Yu C, et al. Classification and differentiation between kidney Yang and Yin decficiency syndromes in TCM based on decision tree analysis method. Int J Clin Exp Med 2016; 11: 21888-99. |
| 8 | Hutchison CAr, Newbold JE, Potter SS, Edgell MH. Maternal inheritance of mammalian mitochondrial DNA. Nature 1974; 5475: 536-8. |
| 9 | Luo SM, Ge ZJ, Wang ZW, et al. Unique insights into maternal mitochondrial inheritance in mice. Proc Natl Acad Sci 2013; 32: 13038-43. |
| 10 | Hendriks KDW, Brüggenwirth IMA, Maassen H, et al. Renal temperature reduction progressively favors mitochondrial ROS production over respiration in hypothermic kidney preservation. J Transl Med 2019; 1: 265. |
| 11 | Mollica MP, Lionetti L, Crescenzo R, et al. Cold exposure differently influences mitochondrial energy efficiency in rat liver and skeletal muscle. FEBS Lett 2005; 9: 1978-82. |
| 12 | Zhao L, Wu H, Qiu M, et al. Metabolic signatures of kidney Yang deficiency syndrome and protective effects of two herbal extracts in rats using GC/TOF MS. Evid Based Complement Alternat Med 2013; 2013: 540957. |
| 13 | Tang N, Liu L, Qiu H, Shi W, Mao D. Analysis of gene expression and functional changes of adrenal gland in a rat model of kidney Yang deficiency syndrome treated with Sini decoction. Exp Ther Med 2018; 4: 3107-15. |
| 14 | Sheng Z, Zhang L, Zha L, Shi S, Gu T. The pituitary gland in patients with kidney Yang deficiency-the changes in Adrenal cortex system. Shanghai Zhong Yi Yao Da Xue Xue Bao 1979; 2: 34-7. |
| 15 | Shen Z. The location of deficiency syndrome of kidney Yang. Chin Med J (Engl) 1999; 11: 973-5. |
| 16 | Malikov D. Traditional Chinese Medicine approach to hypothyroidism. Int J Complementary Altern Med 2016; 1: 00142. |
| 17 | Jang Y, Kim JH, Lee H, Lee K, Ahn SH. A quantile regression approach to explain the relationship of fatigue and cortisol, cytokine among Koreans with hepatitis B. Sci rep 2018; 1: 16434. |
| 18 | Adam EK, Quinn ME, Tavernier R, McQuillan MT, Dahlke KA, Gilbert KE. Diurnal cortisol slopes and mental and physical health outcomes: a systematic review and Meta-analysis. Psychoneuro-endocrinology 2017; 83: 25-41. |
| 19 | Ruiz-Nú?ez B, Tarasse R, Vogelaar EF, Janneke Dijck-Brouwer DA, Muskiet FAJ.Higher prevalence of "Low T3 Syndrome" in patients with chronic fatigue syndrome: a case-control study. Front Endocrinol 2018; 9: 97. |
| 20 | Rajagopal MC, Brown JW, Gelda D, et al. Transient heat release during induced mitochondrial proton uncoupling. Commun Biol 2019; 1: 279. |
| 21 | Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ. Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes Dev 2010; 14: 1507-18. |
| 22 | Miotto PM, McGlory C, Holloway TM, Phillips SM, Holloway GP. Sex-differences in mitochondrial respiratory function in human skeletal muscle. Am J Physiol: Regul, Integr Comp Physiol 2018; 6: R909-15. |
| 23 | Pinti MV, Fink GK, Hathaway QA, Durr AJ, Kunovac A, Hollander JM.Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis. AJP Endocrino Metab 2019; 2: E268- 85. |
| 24 | You B, Dun Y, Zhang W, et al. Anti-insulin resistance effects of salidroside through mitochondrial quality control. J Endocrinol 2020; 2: 383. |
| 25 | Koves TR, Ussher JR, Noland RC, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell metab 2008; 7: 45-56. |
| 26 | Lionetti L, Mollica MP, Crescenzo R, et al. Skeletal muscle subsarcolemmal mitochondrial dysfunction in high-fat fed rats exhibiting impaired glucose homeostasis. Int J Obes 2007; 10: 1596-604. |
| 27 | Li WH, Li QJ, Li WZ, et al. The Fourier transform infrared spectra of the key organs derived from Kidney (Shen)-Yang deficiency syndrome mice. Chin J Integr Med 2014; 11: 829-34. |
| 28 | Lyttleton J. 12 - Diet and lifestyle. In: LyttletonJ, Treatment of infertility with Chinese Medicine Second Edition: Churchill Livingstone 2013:ed.406-40. |
| 29 | Chen H, Ng JPM, Bishop DP, Milthorpe BK, Valenzuela SM. Gold nanoparticles as cell regulators: beneficial effects of gold nanoparticles on the metabolic profile of mice with pre-existing obesity. J Nanobiotechnol 2018; 1: 88. |
| 30 | Chen H, Ng JPM, Tan Y, et al. Gold nanoparticles improve meta-bolic profile of mice fed a high-fat diet. J Nanobiotechnol 2018; 1: 11. |
| 31 | Komalla V, Sheikholeslami B, Li G, et al. Impact of a cargo-less liposomal formulation on dietary obesity-related metabolic disorders in mice. Int J Mol Sci 2020; 21: 7640. |
| 32 | Chen H, Simar D, Pegg K, Saad S, Palmer C, Morris M. Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents. Diabetologia 2014; 3: 614-22. |
| 33 | Chan YL, Saad S, Al-Odat I, et al. Maternal L-Carnitine supplementation improves brain health in offspring from cigarette smoke exposed mothers. Front Mol Neurosci 2017; 10: 33. |
| 34 | Lyttleton J. 4-diagnosis and treatment of female infertility. In: LyttletonJ,ed. Treatment of Infertility with Chinese Medicine (Second Edition): Churchill Livingstone; 2013: 66-139. |
| 35 | Ray B, Mallick HN, Kumar VM. Changes in thermal preference, sleep-wakefulness, body temperature and locomotor activity of rats during continuous recording for 24 hours. Behav Brain Res 2004; 2: 519-26. |
| 36 | Cedikova M, Kripnerová M, Dvorakova J, et al. Mitochondria in white, brown, and beige adipocytes. Stem Cells Int 2016; 2016: 6067349. |
| 37 | Argyropoulos G, Harper ME. Uncoupling proteins and thermoregulation. J Appl Physiol 2002; 5: 2187-98. |
| 38 | Enerback S, Jacobsson A, Simpson EM, et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 1997; 6628: 90-4. |
| 39 | Lee SH, Kwak SC, Kim DK, et al. Effects of Huangbai (Phellodendri Cortex) and three other herbs on GnRH and GH levels in GT1-7 and GH3 cells. Evidence-based complementary Altern Med: eCAM 2016;2016: 9389028. |
| 40 | Xian YF, Mao QQ, Ip SP, Lin ZX, Che CT. Comparison on the anti-inflammatory effect of Cortex Phellodendri Chinensis and Cortex Phellodendri amurensis in 12-O-tetradecanoyl-phorbol-13-acetate-induced ear edema in mice. J Ethnopharmacol 2011; 3: 1425-30. |
| 41 | Sun Y, Lenon GB, Yang AWH. Phellodendri Cortex:a phytochemical, pharmacological, and pharmacokinetic review. Evidence-based complementary Altern Med: eCAM 2019; 2019: 7621929. |
| 42 | Ravussin E, Galgani JE. The implication of brown adipose tissue for humans. Annu Rev Nutr 2011; 31: 33-47. |
| 43 | Shu Y, Jia J, Xu XL, Wang ZX. Observation on pulse hemodynamics in 57 patients with kidney deficiency. Neimenggu Zhong Yi Yao 2000; 4: 5-6. |
| 44 | Cecchino GN, Seli E, Alves da Motta EL, García-Velasco JA. The role of mitochondrial activity in female fertility and assisted reproductive technologies: overview and current insights. Reprod BioMed Online 2018; 6: 686-97. |
| 45 | Kumar DP, Sangeetha N. Mitochondrial DNA mutations and male infertility. Indian J Hum Genet 2009; 3: 93-7. |
| 46 | Handschin C, Choi CS, Chin S, et al. Abnormal glucose homeostasis in skeletal muscle specific PGC-1alpha knockout mice reveals skeletal muscle pancreatic b cell crosstalk. J Clin Invest 2007; 11: 3463-74. |
| 47 | Gerhart-Hines Z, Rodgers JT, Bare O, et al. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 2007; 7: 1913-23. |
| 48 | Zhang W, Wang W, Shi T, et al. Changes of plasma lipid peroxide, high-density lipoprotein cholesterol, and its subcomponent levels in elderly patients with kidney deficiency. Zhong Yi Za Zhi 1989; 2: 43-6. |
| 49 | Liu F, Shan L. An exploration on TCM syndrome differentiation rules and clinical syndromes distribution of hyperlipidemia. Zhong Yi Ling Chuang Za Zhi 2017; 7: 47-8. |
| 50 | Simar D, Chen H, Lambert K, Mercier J, Morris MJ. Interaction between maternal obesity and post-natal over-nutrition on skeletal muscle metabolism. Nutr Metab Cardiovasc Dis 2011; 22: 269-76. |
| 51 | Chan YL, Saad S, Simar D, et al. Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams. Int J Dev Neurosci 2015; 46: 67-75. |
| 52 | Pullinger CR, Eng C, Salen G, et al. Human cholesterol 7 alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J Clin Invest 2002; 1: 109-17. |
| 53 | Li T, Owsley E, Matozel M, Hsu P, Novak CM, Chiang JY. Transgenic expression of cholesterol 7alpha-hydroxylase in the liver prevents high-fat diet-induced obesity and insulin resistance in mice. Hepatology 2010; 2: 678-90. |
/
| 〈 |
|
〉 |