|
|
Effects of urolithin A on browning of white adipose in aged mice fed on a high-fat diet |
LIU Xingyu1, LI Hui2, LI Jing3, WANG Ying4, ZHAO Lisheng4, FENG Chunzhen4 |
1. the First Healthcare Department, the Second Medical Center of PLA General Hospital, Beijing 100048, China; 2. Department of Geriatrics, Mudanjiang Hospital of Beidahuang Group, Jixi 158300, China; 3. Department of Stomatology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China; 4. Department of Stomatology, the First Medical Center of PLA General Hospital, Beijing 100853, China |
|
|
Abstract Objective To investigate the effects of urolithin A on browning of white adipose in aged mice fed on a high-fat diet. Methods Eighteen aged mice were randomly divided into control group, high-fat diet (HFD) group and urolithin A administration group (UA), with 6 mice in each group. UA group was given urolithin A (Tween-80 aid solution), control group and HFD group were given the same dose of Tween-80. After the experiment, the body weight and heat production were detected, the morphology of adipocytes was observed by HE staining. qRT-PCR and Western blot were used to investigate mRNA and protein levels of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ (PPARγ) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Results Compared with the control group, the body weight of HFD group significantly increased, the heat production of the daytime[(0.45±0.03) kcal/h vs. (0.62±0.05) kcal/h] and nighttime[(0.49±0.05) kcal/h vs. (0.73±0.06) kcal/h] significantly decreased(P<0.05), and the cell size of white adipose tissue increased. Moreover, UCP1, PPARγ and PGC-1α expressions decreased (P<0.05). However, urolithin A intervention reduced the body weight of high-fat diet mice, increased daytime heat production [(0.57±0.03) kcal/h vs. (0.45±0.03) kcal/h] and nighttime heat production [(0.69±0.07) kcal/h vs. (0.49±0.05) kcal/h], and promoted the transcriptional expression of UCP1, PPARγ and PGC-1α expressions (P<0.05). Conclusions Urolithin A can promote the browning of white adipose tissue in aged mice fed on a high-fat diet.
|
Received: 20 December 2022
|
|
|
|
|
[1] |
Zhu B, Li Y, Xiang L, et al. Alogliptin improves survival and health of mice on a high-fat diet[J]. Aging Cell, 2019,18(2):e12883.
|
[2] |
柳 杨,田亚丽,古丽海夏·哈勒玛合拜,等. 尿石素A对2型糖尿病小鼠脂肪组织胰岛素抵抗的影响[J]. 中成药, 2020,42(7):1894-1898.
|
[3] |
Zhang Y, Jiang L, Su P, et al. Urolithin A suppresses tumor progression and induces autophagy in gastric cancer via the PI3K/Akt/mTOR pathway[J]. Drug Dev Res, 2022. DOI: 10.1002/ddr.22021.
|
[4] |
Mehra S, Srinivasan S, Singh S, et al. Urolithin A attenuates severity of chronic pancreatitis associated with continued alcohol intake by inhibiting PI3K/AKT/mTOR signaling[J]. Am J Physiol Gastrointest Liver Physiol, 2022,323(4):G375-G386.
|
[5] |
D′Amico D, Olmer M, Fouassier A M, et al. Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis[J]. Aging Cell, 2022,21(8):e13662. .
|
[6] |
Cho S I, Jo E R, Song H. Urolithin A attenuates auditory cell senescence by activating mitophagy[J]. Sci Rep, 2022,12(1):7704.
|
[7] |
Xia B, Shi X C, Xie B C, et al. Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice[J]. PLoS Biol, 2020,18(3):e3000688.
|
[8] |
Huang J R, Zhang M H, Chen Y J, et al. Urolithin A ameliorates obesity-induced metabolic cardiomyopathy in mice via mitophagy activation[J]. Acta Pharmacol Sin, 2022. DOI: 10.1038/s41401-022-00919-1.
|
[9] |
张晓静,李 屹,朱 琳,等. 棕色脂肪细胞分化的分子调控及研究进展[J]. 武警医学, 2020,31(6):539-541.
|
[10] |
何凯悦,徐晓丽,石凌峰,等. 髓源性生长因子对肥胖小鼠白色脂肪棕色化的影响[J]. 中华糖尿病杂志, 2022, 14(4):352-359.
|
[11] |
杨文朋,吴方丽,田萧羽,等. 生长分化因子11对炎症微环境中兔BMSCs成骨分化的影响[J]. 北京口腔医学, 2022,30(1):21-24.
|
[12] |
Zhao W, Shi F, Guo Z, et al. Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells[J]. Mol Carcinog, 2018,57(2):193-200.
|
[13] |
Boakye Y D, Groyer L, Heiss E H. An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages[J]. Biochim Biophys Acta Gen Subj, 2018,1862(1):61-70.
|
[14] |
Piwowarski J P, Kiss A K, Granica S, et al. Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages[J]. Mol Nutr Food Res, 2015,59(11):2168-2177.
|
[15] |
Ryu D, Mouchiroud L, Andreux P A, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents[J]. Nat Med, 2016,22(8):879-888.
|
[16] |
Li S, Li Y, Xiang L, et al. Sildenafil induces browning of subcutaneous white adipose tissue in overweight adults[J]. Metabolism, 2018,78:106-117.
|
[17] |
Ahmadian M, Suh J M, Hah N, et al. PPARγsignaling and metabolism: the good, the bad and the future[J]. Nat Med, 2013,19(5):557-566.
|
[18] |
Gao R, Chen W, Yan H, et al. PPARγ agonist rosiglitazone switches fuel preference to lipids in promoting thermogenesis under cold exposure in C57BL/6 mice[J]. J Proteomics, 2018,176:24-36.
|
[19] |
Zhang Z, Zhang H, Li B, et al. Berberine activates thermogenesis in white and brown adipose tissue[J]. Nat Commun, 2014,5:5493.
|
[20] |
Luo X, Li J, Zhang H, et al. Irisin promotes the browning of white adipocytes tissue by AMPKα1 signaling pathway[J]. Res Vet Sci, 2022,152:270-276.
|
[21] |
Zhu B, Li Y, Mei W, et al. Alogliptin improves endothelial function by promoting autophagy in perivascular adipose tissue of obese mice through a GLP-1-dependent mechanism[J]. Vascul Pharmacol, 2019,115:55-63.
|
[22] |
Ko M S, Yun J Y, Baek I J, et al. Mitophagy deficiency increases NLRP3 to induce brown fat dysfunction in mice[J]. Autophagy, 2021,17(5):1205-1221.
|
[23] |
Yau W W, Singh B K, Lesmana R, et al. Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy[J]. Autophagy, 2019,15(1):131-150.
|
[24] |
Luan P, D′Amico D, Andreux P A, et al. Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy[J]. Sci Transl Med, 2021,13(588):319.
|
|
|
|