PMID- 36797178
OWN - NLM
STAT- MEDLINE
DCOM- 20230404
LR  - 20230404
IS  - 1525-3198 (Electronic)
IS  - 0022-0302 (Linking)
VI  - 106
IP  - 4
DP  - 2023 Apr
TI  - Tandem mass tag-based quantitative proteomics analysis reveals the effects of the 
      alpha-lactalbumin peptides GINY and DQW on lipid deposition and oxidative stress in 
      HepG2 cells.
PG  - 2271-2288
LID - S0022-0302(23)00052-8 [pii]
LID - 10.3168/jds.2022-22511 [doi]
AB  - The objective of this study was to investigate the mechanism by which the 
      alpha-lactalbumin peptides Gly-Ile-Asn-Tyr (GINY) and Asp-Gln-Trp (DQW) ameliorate 
      free fatty acid-induced lipid deposition in HepG2 cells. The results show that 
      GINY and DQW reduced triglyceride, total cholesterol, and free fatty acid levels 
      significantly in free fatty acid-treated HepG2 cells. Based on proteomic 
      analysis, GINY and DQW alleviated lipid deposition and oxidative stress mainly 
      through the peroxisome proliferator-activated receptor (PPAR) pathway, fatty acid 
      metabolism, oxidative phosphorylation, and response to oxidative stress. In vitro 
      experiments confirmed that GINY and DQW upregulated the mRNA and protein 
      expression of fatty acid beta-oxidation-related and oxidative stress-related genes, 
      and downregulated the mRNA and protein expression of lipogenesis-related genes by 
      activating peroxisome proliferator-activated receptor alpha (PPARalpha). Meanwhile, GINY 
      and DQW reduced free fatty acid-induced lipid droplet accumulation and reactive 
      oxygen species generation, and enhanced the mitochondrial membrane potential and 
      ATP levels. Furthermore, GINY and DQW enhanced carnitine palmitoyl-transferase 1a 
      (CPT-1a) and superoxide dismutase activities, and diminished acetyl-coenzyme A 
      carboxylase 1 (ACC1) and fatty acid synthase (FASN) activities in a 
      PPARalpha-dependent manner. Interestingly, GW6471 (a PPARalpha inhibitor) weakened the 
      effects of GINY and DQW on the PPARalpha pathway. Hence, our findings suggest that 
      GINY and DQW have the potential to alleviate nonalcoholic fatty liver disease by 
      activating the PPARalpha pathway.
CI  - The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American 
      Dairy Science Association(R). This is an open access article under the CC BY 
      license (http://creativecommons.org/licenses/by/4.0/).
FAU - Chen, Haoran
AU  - Chen H
AD  - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, 
      Harbin, 150001, Heilongjiang, China.
FAU - Qi, Xiaofen
AU  - Qi X
AD  - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, 
      Harbin, 150001, Heilongjiang, China.
FAU - Guan, Kaifang
AU  - Guan K
AD  - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, 
      Harbin, 150001, Heilongjiang, China.
FAU - Wang, Rongchun
AU  - Wang R
AD  - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, 
      Harbin, 150001, Heilongjiang, China.
FAU - Li, Qiming
AU  - Li Q
AD  - New Hope Dairy Co. Ltd., Chengdu, 610063, Sichuan, China; Dairy Nutrition and 
      Function, Key Laboratory of Sichuan Province, Chengdu, 610000, Sichuan, China.
FAU - Ma, Ying
AU  - Ma Y
AD  - School of Chemistry and Chemical Engineering, Harbin Institute of Technology, 
      Harbin, 150001, Heilongjiang, China. Electronic address: maying@hit.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230214
PL  - United States
TA  - J Dairy Sci
JT  - Journal of dairy science
JID - 2985126R
RN  - 9013-90-5 (Lactalbumin)
RN  - 0 (PPAR alpha)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Peptides)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Hep G2 Cells
MH  - *Lactalbumin/pharmacology/metabolism
MH  - PPAR alpha/genetics
MH  - Fatty Acids, Nonesterified/metabolism
MH  - Proteomics
MH  - *Non-alcoholic Fatty Liver Disease/metabolism/veterinary
MH  - Oxidative Stress
MH  - Lipid Metabolism
MH  - Peptides/pharmacology/metabolism
MH  - RNA, Messenger/metabolism
MH  - Liver/metabolism
OTO - NOTNLM
OT  - DQW
OT  - GINY
OT  - lipid deposition
OT  - proteomic
OT  - alpha-lactalbumin
EDAT- 2023/02/17 06:00
MHDA- 2023/04/04 06:42
CRDT- 2023/02/16 22:06
PHST- 2022/07/12 00:00 [received]
PHST- 2022/09/28 00:00 [accepted]
PHST- 2023/04/04 06:42 [medline]
PHST- 2023/02/17 06:00 [pubmed]
PHST- 2023/02/16 22:06 [entrez]
AID - S0022-0302(23)00052-8 [pii]
AID - 10.3168/jds.2022-22511 [doi]
PST - ppublish
SO  - J Dairy Sci. 2023 Apr;106(4):2271-2288. doi: 10.3168/jds.2022-22511. Epub 2023 
      Feb 14.