Sesamol Counteracts on Metabolic Disorders of Middle-aged Alimentary Obese Mice Through Regulating Skeletal Muscle Glucose and Lipid Metabolism

Overview

Journal Food Nutr Res

Specialty Nutritional Sciences

Date 2022 Apr 6

PMID 35382382

Authors

Min-Min Hu

Ji-Hua Chen

Quan-Quan Zhang

Zi-Yu Song

Horia Shaukat

Hong Qin

Affiliations

Soon will be listed here.

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.

References

Pirinen E, Canto C, Jo Y, Morato L, Zhang H, Menzies K . Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab. 2014; 19(6):1034-41. PMC: 4047186. DOI: 10.1016/j.cmet.2014.04.002. View

Shah S, Yoon G, Chung S, Abid M, Kim T, Lee H . Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer's disease neuropathological deficits. Mol Psychiatry. 2016; 22(3):407-416. PMC: 5322276. DOI: 10.1038/mp.2016.23. View

Ferre P, Foufelle F . SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res. 2007; 68(2):72-82. DOI: 10.1159/000100426. View

Dong L, Zhang Y, Yang L, Liu G, Ye J, Wang H . Effects of a High-Fat Diet on Adipose Tissue CD8+ T Cells in Young vs. Adult Mice. Inflammation. 2017; 40(6):1944-1958. DOI: 10.1007/s10753-017-0635-0. View

Silva V, Katashima C, Lenhare L, Silva C, Morari J, Camargo R . Chronic exercise reduces hypothalamic transforming growth factor-β1 in middle-aged obese mice. Aging (Albany NY). 2017; 9(8):1926-1940. PMC: 5611986. DOI: 10.18632/aging.101281. View

Qin H, Xu H, Yu L, Yang L, Lin C, Chen J . Sesamol intervention ameliorates obesity-associated metabolic disorders by regulating hepatic lipid metabolism in high-fat diet-induced obese mice. Food Nutr Res. 2019; 63. PMC: 6814895. DOI: 10.29219/fnr.v63.3637. View

Macia M, Pecchi E, Desrois M, Lan C, Vilmen C, Portha B . 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. View

Jung T, Lee S, Kim H, Bang J, Abd El-Aty A, Hacimuftuoglu A . 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):1-11. PMC: 6137187. DOI: 10.1038/s12276-018-0147-5. View

Sung M, Koonen D, Soltys C, Jacobs R, Febbraio M, Dyck J . Increased CD36 expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction. J Mol Med (Berl). 2011; 89(5):459-69. DOI: 10.1007/s00109-010-0720-4. View

10.

Li Y, Pan H, Zhang X, Wang H, Liu S, Zhang H . Geniposide Improves Glucose Homeostasis via Regulating FoxO1/PDK4 in Skeletal Muscle. J Agric Food Chem. 2019; 67(16):4483-4492. DOI: 10.1021/acs.jafc.9b00402. View

11.

Kitessa S, Abeywardena M . 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). PMC: 4997379. DOI: 10.3390/nu8080466. View

12.

Chia C, Egan J, Ferrucci L . Age-Related Changes in Glucose Metabolism, Hyperglycemia, and Cardiovascular Risk. Circ Res. 2018; 123(7):886-904. PMC: 6205735. DOI: 10.1161/CIRCRESAHA.118.312806. View

13.

Ye Z, Wang S, Zhang C, Zhao Y . Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids. Front Endocrinol (Lausanne). 2020; 11:617. PMC: 7506139. DOI: 10.3389/fendo.2020.00617. View

14.

Ko K, Woo J, Bae J, Roh H, Lee Y, Shin K . Exercise training improves intramuscular triglyceride lipolysis sensitivity in high-fat diet induced obese mice. Lipids Health Dis. 2018; 17(1):81. PMC: 5902881. DOI: 10.1186/s12944-018-0730-8. View

15.

Mukund K, Subramaniam S . Skeletal muscle: A review of molecular structure and function, in health and disease. Wiley Interdiscip Rev Syst Biol Med. 2019; 12(1):e1462. PMC: 6916202. DOI: 10.1002/wsbm.1462. View

16.

Gagnon A, Antunes T, Ly T, Pongsuwan P, Gavin C, Lochnan H . Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo. Metabolism. 2009; 59(4):547-53. DOI: 10.1016/j.metabol.2009.08.018. View

17.

Kwon S, Seok S, Yau P, Li X, Kemper B, Kemper J . 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):17312-17323. PMC: 5655509. DOI: 10.1074/jbc.M117.778720. View

18.

Kim M, Park K . Association between phytochemical index and metabolic syndrome. Nutr Res Pract. 2020; 14(3):252-261. PMC: 7263893. DOI: 10.4162/nrp.2020.14.3.252. View

19.

Fan L, Cahill-Smith S, Geng L, Du J, Brooks G, Li J . Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function. Free Radic Biol Med. 2017; 108:940-951. PMC: 5489050. DOI: 10.1016/j.freeradbiomed.2017.05.008. View

20.

McAinch A, Cornall L, Watts R, Hryciw D, OBrien P, Cameron-Smith D . Increased pyruvate dehydrogenase kinase expression in cultured myotubes from obese and diabetic individuals. Eur J Nutr. 2014; 54(7):1033-43. DOI: 10.1007/s00394-014-0780-2. View