Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism

  • Min-Min Hu Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University
  • Ji-Hua Chen Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University
  • Quan-Quan Zhang Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University
  • Zi-Yu Song Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University
  • Horia Shaukat Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University
  • Hong Qin Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University https://orcid.org/0000-0002-4578-5118
Keywords: sesamol, obesity, aging, skeletal muscle, glucose metabolism, lipid metabolism

Abstract

Background: Globally, obesity is a significant public problem, especially when aging. Sesamol, a phenolic lignan present in sesame seeds, might have a positive effect on high-fat diet (HFD)-induced obesity associated with aging.

Objective: The purpose of current research study was to explore salutary effects and mechanisms of sesamol in treating alimentary obesity and associated metabolic syndrome in middle-aged mice.

Methods: C57BL/6J mice aged 4–6 weeks and 6–8 months were assigned to the young normal diet group, middle-aged normal diet group, middle-aged HFD group, and middle-aged HFD + sesamol group. At the end of experiment, glucose tolerance test and insulin tolerance test were performed; the levels of lipids and oxidative stress-related factors in the serum and skeletal muscle were detected using chemistry reagent kits; lipid accumulation in skeletal muscle was observed by oil red O staining; the expressions of muscular glucose and lipid metabolism associated proteins were measured by Western blotting.

Results: Sesamol decreased the body weight and alleviated obesity-associated metabolism syndrome in middle-aged mice, such as glucose intolerance, insulin resistance, dyslipidemia, and oxidative stress. Moreover, muscular metabolic disorders were attenuated after treatment with sesamol. It increased the expression of glucose transporter type-4 and down-regulated the protein levels of pyruvate dehydrogenase kinase isozyme 4, implying the increase of glucose uptake and oxidation. Meanwhile, sesamol decreased the expression of sterol regulatory element binding protein 1c and up-regulated the phosphorylation of hormone-sensitive lipase and the level of carnitine palmityl transferase 1α, which led to the declined lipogenesis and the increased lipolysis and lipid oxidation. In addition, the SIRT1/AMPK signaling pathway was triggered by sesamol, from which it is understood how sesamol enhances glucose and lipid metabolism.

Conclusions: Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism, which might be associated with the stimulation of the SIRT1/AMPK pathway.

Downloads

Download data is not yet available.

References

ol>
  • Chia CW, Egan JM, Ferrucci L. Age-related changes in glucose metabolism, hyperglycemia, and cardiovascular risk. Circ Res 2018; 123(7): 886–904. doi: 10.1161/circresaha.118.312806

  • Gong Z, Tas E, Yakar S, Muzumdar R. Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging. Mol Cell Endocrinol 2017; 455: 115–30. doi: 10.1016/j.mce.2016.12.022

  • Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. New Engl J Med 2017; 376(3): 254–66. doi: 10.1056/NEJMra1514009

  • Inoue Y, Qin B, Poti J, Sokol R, Gordon-Larsen P. Epidemiology of obesity in adults: latest trends. Curr Obes Rep 2018; 7(4): 276–88. doi: 10.1007/s13679-018-0317-8

  • Lawan A, Min K, Zhang L, Canfran-Duque A, Jurczak MJ, Camporez JPG, et al. Skeletal muscle–specific deletion of MKP-1 reveals a p38 MAPK/JNK/Akt signaling node that regulates obesity-induced insulin resistance. Diabetes 2018; 67(4): 624. doi: 10.2337/db17-0826

  • Kitessa SM, Abeywardena MY. Lipid-induced insulin resistance in skeletal muscle: the chase for the culprit goes from total intramuscular fat to lipid intermediates, and finally to species of lipid intermediates. Nutrients 2016; 8(8): 446. doi: 10.3390/nu8080466

  • Macia M, Pecchi E, Desrois M, Lan C, Vilmen C, Portha B, et al. Exercise training impacts exercise tolerance and bioenergetics in gastrocnemius muscle of non-obese type-2 diabetic Goto-Kakizaki rat in vivo. Biochimie 2018; 148: 36–45. doi: 10.1016/j.biochi.2018.02.014

  • Lee MT, Lin WC, Yu B, Lee TT. Antioxidant capacity of phytochemicals and their potential effects on oxidative status in animals – a review. Asian Australas J Anim Sci 2017; 30(3): 299–308. doi: 10.5713/ajas.16.0438

  • Jung TW, Lee SH, Kim H-C, Bang JS, Abd El-Aty AM, Hacımüftüoğlu A, et al. METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice. Exp Mol Med 2018; 50(9): 122. doi: 10.1038/s12276-018-0147-5

  • Chung E, Campise SN, Joiner HE, Tomison MD, Kaur G, Dufour JM, et al. Effect of annatto-extracted tocotrienols and green tea polyphenols on glucose homeostasis and skeletal muscle metabolism in obese male mice. J Nutr Biochem 2019; 67: 36–43. doi: 10.1016/j.jnutbio.2019.01.021

  • Moller DE, Kaufman KD. Metabolic syndrome: a clinical and molecular perspective. Annu Rev Med 2005; 56: 45–62. doi: 10.1146/annurev.med.56.082103.104751

  • Francini-Pesenti F, Spinella P, Calò LA. Potential role of phytochemicals in metabolic syndrome prevention and therapy. Diabetes Metab Syndr Obes 2019; 12: 1987–2002. doi: 10.2147/dmso.s214550

  • Kim M, Park K. Association between phytochemical index and metabolic syndrome. Nutr Res Pract 2020; 14(3): 252–61. doi: 10.4162/nrp.2020.14.3.252

  • Majdalawieh AF, Mansour ZR. Sesamol, a major lignan in sesame seeds (Sesamum indicum): anti-cancer properties and mechanisms of action. Eur J Pharmacol 2019; 855: 75–89. doi: 10.1016/j.ejphar.2019.05.008

  • Ren B, Yuan T, Zhang XL, Wang LF, Pan JR, Liu Y, et al. Protective effects of sesamol on systemic inflammation and cognitive impairment in aging mice. J Agr Food Chem 2020; 68(10): 3099–111. doi: 10.1021/acs.jafc.9b07598

  • Xu HY, Yu L, Chen JH, Yang LN, Lin C, Shi XQ, et al. Sesamol alleviates obesity-related hepatic steatosis via activating hepatic PKA pathway. Nutrients 2020; 12(2): 329. doi: 10.3390/nu12020329

  • Qin H, Xu HY, Yu L, Yang LN, Lin C, Chen JH. Sesamol intervention ameliorates obesity-associated metabolic disorders by regulating hepatic lipid metabolism in high-fat diet-induced obese mice. Food Nutr Res 2019; 63: 3637. doi: 10.29219/fnr.v63.3637

  • Dong LJ, Zhang Y, Yang L, Liu GY, Ye JP, Wang H. Effects of a high-fat diet on adipose tissue CD8+ T cells in young vs. adult mice. Inflammation 2017; 40(6): 1944–58. doi: 10.1007/s10753-017-0635-0

  • Ye ZH, Wang SY, Zhang CM, Zhao Y. Coordinated modulation of energy metabolism and inflammation by branched-chain amino acids and fatty acids. Front Endocrinol (Lausanne) 2020; 11: 617. doi: 10.3389/fendo.2020.00617

  • Lu J, Fang BC, Zheng YY, Yu X, Huang GR, Wang ZN, et al. 1,3-dichloro-2-propanol induced lipid accumulation in HepG2 cells through cAMP/protein kinase A and AMP-activated protein kinase pathways via Gi/o-coupled receptors. Environ Toxicol Pharmacol 2017; 55: 118–26. doi: 10.1016/j.etap.2017.07.013

  • Li CX, Gao JG, Wan XY, Chen Y, Xu CF, Feng ZM, et al. Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways. World J Gastroenterol 2019; 25(34): 5120–33. doi: 10.3748/wjg.v25.i34.5120

  • Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809): 239–47. doi: 10.1038/35041687

  • Fan LM, Cahill-Smith S, Geng L, Du J, Brooks G, Li J-M. Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function. Free Radic Biol Med 2017; 108: 940–51. doi: 10.1016/j.freeradbiomed.2017.05.008

  • Freisling H, Arnold M, Soerjomataram I, O’Doherty MG, Ordóñez-Mena JM, Bamia C, et al. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe. Br J Canc 2017; 116(11): 1486–97. doi: 10.1038/bjc.2017.106

  • Silva VRR, Katashima CK, Lenhare L, Silva CGB, Morari J, Camargo RL, et al. Chronic exercise reduces hypothalamic transforming growth factor-β1 in middle-aged obese mice. Aging (Albany NY) 2017; 9(8): 1926–40. doi: 10.18632/aging.101281

  • Jakubczyk A, Karaś M, Złotek U, Szymanowska U. Identification of potential inhibitory peptides of enzymes involved in the metabolic syndrome obtained by simulated gastrointestinal digestion of fermented bean (Phaseolus vulgaris L.) seeds. Food Res Int 2017; 100: 489–96. doi: 10.1016/j.foodres.2017.07.046

  • Liu ZG, Qiao QL, Sun YL, Chen YW, Ren B, Liu XB. Sesamol ameliorates diet-induced obesity in C57BL/6J mice and suppresses adipogenesis in 3T3-L1 cells via regulating mitochondria-lipid metabolism. Mol Nutr Food Res 2017; 61(8): 1600717. doi: 10.1002/mnfr.201600717

  • Lee DH, Chang S-H, Yang DK, Song N-J, Yun UJ, Park KW. Sesamol increases UCP1 expression in white adipose tissues and stimulates energy expenditure in high-fat diet-fed obese mice. Nutrients 2020; 12(5): 1459. doi: 10.3390/nu12051459

  • Mukund K, Subramaniam S. Skeletal muscle: a review of molecular structure and function, in health and disease. Wiley Interdiscip Rev Syst Biol Med 2020; 12(1): e1462. doi: 10.1002/wsbm.1462

  • Gan ML, Shen LY, Liu L, Guo ZX, Wang SJ, Chen L, et al. miR-222 is involved in the regulation of genistein on skeletal muscle fiber type. J Nutr Biochem 2020; 80: 108320. doi: 10.1016/j.jnutbio.2019.108320

  • Wu HZ, Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity. J Clin Investig 2017; 127(1): 43–54. doi: 10.1172/jci88880

  • Moon SS. Low skeletal muscle mass is associated with insulin resistance, diabetes, and metabolic syndrome in the Korean population: the Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010. Endocr J 2014; 61(1): 61–70. doi: 10.1507/endocrj.ej13-0244

  • Biolo G, Cederholm T, Muscaritoli M. Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: from sarcopenic obesity to cachexia. Clin Nutr 2014; 33(5): 737–48. doi: 10.1016/j.clnu.2014.03.007

  • Pirinen E, Cantó C, Jo YS, Morato L, Zhang H, Menzies KJ, et al. Pharmacological inhibition of poly (ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metabol 2014; 19(6): 1034–41. doi: 10.1016/j.cmet.2014.04.002

  • Zacharewicz E, Hesselink MKC, Schrauwen P. Exercise counteracts lipotoxicity by improving lipid turnover and lipid droplet quality. J Intern Med 2018; 284(5): 505–18. doi: 10.1111/joim.12729

  • Akhmedov D, Berdeaux R. The effects of obesity on skeletal muscle regeneration. Front Physiol 2013; 4: 371. doi: 10.3389/fphys.2013.00371

  • Deng Z, Yu H, Yang Z, Hu L, Liu Q, Wang Y, et al. Gly-Pro-Ala peptide and FGSHF3 exert protective effects in DON-induced toxicity and intestinal damage via decreasing oxidative stress. Food Res Int 2021; 139: 109840. doi: 10.1016/j.foodres.2020.109840

  • Goodpaster BH, Wolf D. Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes. Pediatr Diabetes 2004; 5(4): 219–26. doi: 10.1111/j.1399-543X.2004.00071.x

  • Graham TE, Yuan Z, Hill AK, Wilson RJ. The regulation of muscle glycogen: the granule and its proteins. Acta physiologica (Oxf) 2010; 199(4): 489–98. doi: 10.1111/j.1748-1716.2010.02131.x

  • Gannon NP, Conn CA, Vaughan RA. Dietary stimulators of GLUT4 expression and translocation in skeletal muscle: a mini-review. Mol Nutr Food Res 2015; 59(1): 48–64. doi: 10.1002/mnfr.201400414

  • Li Y, Pan HO, Zhang XT, Wang H, Liu SN, Zhang H, et al. Geniposide improves glucose homeostasis via regulating FoxO1/PDK4 in skeletal muscle. J Agr Food Chem 2019; 67(16): 4483–92. doi: 10.1021/acs.jafc.9b00402

  • McAinch AJ, Cornall LM, Watts R, Hryciw DH, O’Brien PE, Cameron-Smith D. Increased pyruvate dehydrogenase kinase expression in cultured myotubes from obese and diabetic individuals. Eur J Nutr 2015; 54(7): 1033–43. doi: 10.1007/s00394-014-0780-2

  • Ferré P, Foufelle F. SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Hormone Res 2007; 68(2): 72–82. doi: 10.1159/000100426

  • Ko K, Woo J, Bae JY, Roh HT, Lee YH, Shin KO. Exercise training improves intramuscular triglyceride lipolysis sensitivity in high-fat diet induced obese mice. Lipids Health Dis 2018; 17(1): 81. doi: 10.1186/s12944-018-0730-8

  • Gagnon A, Antunes TT, Ly T, Pongsuwan P, Gavin C, Lochnan HA, et al. Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo. Metabol Clin Exp 2010; 59(4): 547–53. doi: 10.1016/j.metabol.2009.08.018

  • Van Hees AMJ, Jans A, Hul GB, Roche HM, Saris WHM, Blaak EE. Skeletal muscle fatty acid handling in insulin resistant men. Obesity 2011; 19(7): 1350–9. doi: 10.1038/oby.2011.10

  • Jambor de Sousa UL, Koss MD, Fillies M, Gahl A, Scheeder MRL, Cardoso MC, et al. CPT1 alpha over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells. Biochem Biophys Res Commun 2005; 338(2): 757–61. doi: 10.1016/j.bbrc.2005.10.016

  • Hardie, D G. AMP-activated protein kinase – an energy sensor that regulates all aspects of cell function. Gene Dev 2011; 25(18): 1895–908. doi: 10.1101/gad.17420111

  • Fu X, Zhu MJ, Zhang SM, Foretz M, Viollet B, Du M. Obesity impairs skeletal muscle regeneration through inhibition of AMPK. Diabetes 2016; 65(1): 188–200. doi: 10.2337/db15-0647

  • Sung MMY, Koonen DPY, Soltys C-LM, Jacobs RL, Febbraio M, Dyck JRB. Increased CD36 expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction. J Mol Med (Berlin) 2011; 89(5): 459–69. doi: 10.1007/s00109-010-0720-4

  • Watt MJ, Dzamko N, Thomas WG, Rose-John S, Ernst M, Carling D, et al. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 2006; 12(5): 541–8. doi: 10.1038/nm1383

  • Shah SA, Yoon GH, Chung SS, Abid MN, Kim TH, Lee HY, et al. Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer’s disease neuropathological deficits. Mol Psychiatr 2017; 22(3): 407–16. doi: 10.1038/mp.2016.23

  • Pardo PS, Boriek AM. SIRT1 regulation in ageing and obesity. Mech Ageing Dev 2020; 188: 111249. doi: 10.1016/j.mad.2020.111249

  • Kwon S, Seok S, Yau P, Li X, Kemper B, Kemper JK. Obesity and aging diminish sirtuin 1 (SIRT1)-mediated deacetylation of SIRT3, leading to hyperacetylation and decreased activity and stability of SIRT3. J Biol Chem 2017; 292(42): 17312–23. doi: 10.1074/jbc.M117.778720

  • Published
    2022-03-17
    How to Cite
    HuM.-M., ChenJ.-H., ZhangQ.-Q., SongZ.-Y., ShaukatH., & QinH. (2022). Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism. Food & Nutrition Research, 66. https://doi.org/10.29219/fnr.v66.8231
    Section
    Original Articles