|Table of Contents|

Dihydromyricetin improves cardiac function in ob/ob mice and its underlying mechanism



Research Field:
Publishing date:



Dihydromyricetin improves cardiac function in ob/ob mice and its underlying mechanism


GONG Xinhua ZHOU Qicheng GU Yeyun ZHU Jundong MI Mantian

Department of Nutrition and Food Hygiene, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Center of Medical Nutrition, College of Military Preventive Medicine, Third Military Medical University, Chongqing, 400038, China


dihydromyricetin insulin resistance cardiac function peroxisome proliferator-activated receptor gamma coactivator 1-alpha fibronectin typeⅢdomain-containing protein 5 ob/ob mice

R151.3; R331.31; R589.2

Objective       To determine the protective effect of dihydromyricetin (DHM) on cardiac function in ob/ob mice (with leptin mutation) and investigate the underlying mechanism. Methods      Thirty-six male ob/ob mice were randomly divided into 3 groups: ob/ob group, ob/ob+DHM 50 mg/kg group, ob/ob+DHM 100 mg/kg group (n=12). Ten C57BL/6J wild type mice are used as normal control (WT). Glucose tolerance and insulin tolerance were measured after 16 weeks’ treatment. Cardiac function was detected by echocardiography. Myocardial histopathology and collagen deposition were detected by HE and Masson staining. The protein expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and fibronectin typeⅢ domain-containing protein 5 (FNDC5) in the myocardium were detected by Western blotting. The expression of FNDC5 in the myocardium was observed by immunohistochemical assay. Results       Glucose tolerance and insulin tolerance were obviously injured in the ob/ob mice than the WT group (P<0.05). In the ob/ob mice, no changes were found in diastolic left ventricular diameter (LVIDd), systolic left ventricular diameter (LVIDs), or ratio of velocity of early filling wave (E) to velocity of late filling wave due to atrial contraction (A) (P>0.05), or myocardial hypertrophy or collagen deposition, but notable decreases were found in short axis fractional shortening (FS) and ejection fraction (EF) (P<0.05), as well as the protein expression levels of PGC-1α and FNDC5 (P<0.05). DHM treatment for 16 weeks could significantly reverse the above changes in the ob/ob mice (P<0.05). Conclusion      DHM ameliorates cardiac function in the ob/ob mice, which might be related to PGC-1α/FNDC5 signalling pathway.


[1]INGELSSON E, SUNDSTR-M J, ARN-V J, et al. Insulin resistance and risk of congestive heart failure[J]. JAMA, 2005, 294(3): 334-341. DOI:10.1001/jama.294.3.334.
[2]SHEN Y, LINDEMEYER A K, GONZALEZ C, et al. Dihydromyricetin as a novel anti-alcohol intoxication medication[J]. J Neurosci, 2012, 32(1): 390-401.DOI:10.1523/JNEUROSCI.463911.2012.
[3]XIA J, GUO S, FANG T, et al. Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways[J]. Food Chem Toxicol, 2014, 66: 7-13.DOI:10.1016/j.fct.2014.01.014.
[4]ZHANG Q, LIU J, LIU B, et al. Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activationdependent mechanism[J]. Sci Rep, 2014, 4: 4628.DOI:10.1038/srep04628.
[5]WU S, LIU B, ZHANG Q, et al. Dihydromyricetin reduced Bcl2 expression via p53 in human hepatoma HepG2 cells[J]. PLoS One, 2013, 8(11): e76886. DOI:10.1371/journal.pone.0076886.
[6]LIAO W, NING Z, MA L, et al. Recrystallization of dihydromyricetin from Ampelopsis grossedentata and its anti-oxidant activity evaluation[J]. Rejuvenation Res, 2014, 17(5): 422-429.DOI:10.1089/rej.2014.1555.
[7]SHI L, ZHANG T, LIANG X, et al. Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway[J]. Mol Cell Endocrinol, 2015, 409: 92-102. DOI:10.1016/j.mce.2015.03.009.
[8]WRANN C D, WHITE J P, SALOGIANNNIS J, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway[J]. Cell Metab, 2013, 18(5): 649-659. DOI:10.1016/j.cmet.2013.09.008.
[9]WITTELES R M, FOWLER M B. Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options[J]. J Am Coll Cardiol, 2008, 51(2): 93-102. DOI:10.1016/j.jacc.2007.10.021.
[10]FANG Z Y, PRINS J B, MARWICK T H. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications[J]. Endocr Rev, 2004, 25(4): 543-567.DOI:10.1210/er.2003-0012.
[11]张平, 郭莹, 张宇, 等. PGC-1α与心脏生理和疾病关系的研究进展[J]. 山东医药, 2012, 52(28): 88-90,93. DOI: 10.3969/j.issn.1002266X.2012.28.037.
ZHANG P, GUO Y, ZHANG Y, et al. Progress in the relation between PGC-1α and cardiac physiology and diseases[J]. Shandong Med J, 2012, 52(28): 88-90,93. DOI:10.3969/j.issn.1002-266X.2012.28.037.
[12]WANG Q, LI C, ZHANG Q, et al. The effect of Chinese herbs and its effective components on coronary heart disease through PPARsPGC1α pathway[J]. BMC Complement Altern Med, 2016, 16(1): 514. DOI:10.1186/s12906-016-1496-z.
[13]XU X, YING Z, CAI M, et al. Exercise ameliorates highfat dietinduced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue[J]. AJP: Regulatory, Integrative and Comparative Physiology, 2011, 300(5): R1115-R1125. DOI:10.1152/ajpregu.00806.2010.
[14]ZADEGAN F G, GHAEDI K, KALANTAR S M, et al. Cardiac differentiation of mouse embryonic stem cells is influenced by a PPAR γ/PGC-1α-FNDC5 pathway during the stage of cardiac precursor cell formation[J]. Eur J Cell Biol, 2015, 94(6): 257-266. DOI:10.1016/j.ejcb.2015.04.002.
[15]AYDIN S, KULOGLU T, AYDIN S, et al. Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle[J]. Peptides, 2014, 52: 68-73.DOI:10.1016/j.peptides.2013.11.024.


Last Update: 2017-08-20