PMID- 36501095
OWN - NLM
STAT- MEDLINE
DCOM- 20221216
LR  - 20221221
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 14
IP  - 23
DP  - 2022 Nov 28
TI  - Oral Administration of Branched-Chain Amino Acids Attenuates Atherosclerosis by 
      Inhibiting the Inflammatory Response and Regulating the Gut Microbiota in 
      ApoE-Deficient Mice.
LID - 10.3390/nu14235065 [doi]
LID - 5065
AB  - Atherosclerosis (AS) is a chronic inflammatory disease that serves as a common 
      pathogenic underpinning for various cardiovascular diseases. Although high 
      circulating branched-chain amino acid (BCAA) levels may represent a risk factor 
      for AS, it is unclear whether dietary BCAA supplementation causes elevated levels 
      of circulating BCAAs and hence influences AS, and the related mechanisms are not 
      well understood. Here, ApoE-deficient mice (ApoE(-/-)) were fed a diet 
      supplemented with or without BCAAs to investigate the effects of BCAAs on AS and 
      determine potential related mechanisms. In this study, compared with the high-fat 
      diet (HFD), high-fat diet supplemented with BCAAs (HFB) reduced the 
      atherosclerotic lesion area and caused a significant decrease in serum 
      cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. BCAA 
      supplementation suppressed the systemic inflammatory response by reducing 
      macrophage infiltration; lowering serum levels of inflammatory factors, including 
      monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), 
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6); and suppressing inflammatory 
      related signaling pathways. Furthermore, BCAA supplementation altered the gut 
      bacterial beta diversity and composition, especially reducing harmful bacteria 
      and increasing probiotic bacteria, along with increasing bile acid (BA) 
      excretion. In addition, the levels of total BAs, primary BAs, 12alpha-hydroxylated 
      bile acids (12alpha-OH BAs) and non-12alpha-hydroxylated bile acids (non-12alpha-OH BAs) in 
      cecal and colonic contents were increased in the HFB group of mice compared with 
      the HFD group. Overall, these data indicate that dietary BCAA supplementation can 
      attenuate atherosclerosis induced by HFD in ApoE(-/-) mice through improved 
      dyslipidemia and inflammation, mechanisms involving the intestinal microbiota, 
      and promotion of BA excretion.
FAU - Li, Ziyun
AU  - Li Z
AUID- ORCID: 0000-0002-1494-194X
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
FAU - Zhang, Ranran
AU  - Zhang R
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
FAU - Mu, Hongna
AU  - Mu H
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
FAU - Zhang, Wenduo
AU  - Zhang W
AD  - Department of Cardiology, Beijing Hospital, National Center of Gerontology, 
      Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      100730, China.
FAU - Zeng, Jie
AU  - Zeng J
AD  - National Center for Clinical Laboratories, Institute of Geriatric Medicine, 
      Chinese Academy of Medical Sciences, Beijing Hospital, National Center of 
      Gerontology, Beijing 100730, China.
FAU - Li, Hongxia
AU  - Li H
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
FAU - Wang, Siming
AU  - Wang S
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
FAU - Zhao, Xianghui
AU  - Zhao X
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
FAU - Chen, Wenxiang
AU  - Chen W
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
AD  - National Center for Clinical Laboratories, Institute of Geriatric Medicine, 
      Chinese Academy of Medical Sciences, Beijing Hospital, National Center of 
      Gerontology, Beijing 100730, China.
FAU - Dong, Jun
AU  - Dong J
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
FAU - Yang, Ruiyue
AU  - Yang R
AUID- ORCID: 0000-0002-2304-6728
AD  - The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of 
      Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 
      Hospital/National Center of Gerontology of National Health Commission, Beijing 
      100730, China.
LA  - eng
GR  - 81672075/National Natural Science Foundation of China/
GR  - 7222156/Beijing Natural Science Foundation/
GR  - 7214250/Beijing Natural Science Foundation/
GR  - 2021-I2M-1-050/CAMS Innovation Fund for Medical Sciences/
GR  - 2021YFE0114200/National Key R&D Program of China/
PT  - Journal Article
DEP - 20221128
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Bile Acids and Salts)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Gastrointestinal Microbiome/physiology
MH  - Amino Acids, Branched-Chain/metabolism
MH  - *Atherosclerosis/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Bile Acids and Salts
MH  - Cholesterol
MH  - Administration, Oral
MH  - Mice, Inbred C57BL
PMC - PMC9739883
OTO - NOTNLM
OT  - atherosclerosis
OT  - bile acids
OT  - branched-chain amino acids
OT  - gut microbiota
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/12 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/11/28
CRDT- 2022/12/11 01:31
PHST- 2022/11/04 00:00 [received]
PHST- 2022/11/25 00:00 [revised]
PHST- 2022/11/25 00:00 [accepted]
PHST- 2022/12/11 01:31 [entrez]
PHST- 2022/12/12 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/11/28 00:00 [pmc-release]
AID - nu14235065 [pii]
AID - nutrients-14-05065 [pii]
AID - 10.3390/nu14235065 [doi]
PST - epublish
SO  - Nutrients. 2022 Nov 28;14(23):5065. doi: 10.3390/nu14235065.