The PKA-SREBP1c Pathway Plays a Key Role in the Protective Effects of Lactobacillus johnsonii JNU3402 Against Diet-Induced Fatty Liver in Mice.

Autor: Hong E; Department of Biological Sciences, College of Natural Sciences, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea., Kang H; Division of Analytical Science, Korea Basic Science Institute, 169-148, Gwahak-ro, Yuseong-gu, Daejeon, 34133, Republic of Korea., Yang G; Department of Biological Sciences, College of Natural Sciences, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea., Oh S; Division of Animal Science, College of Agriculture & Life Sciences, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea., Kim E; Department of Biological Sciences, College of Natural Sciences, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.
Jazyk: angličtina
Zdroj: Molecular nutrition & food research [Mol Nutr Food Res] 2023 Oct; Vol. 67 (20), pp. e2200496. Date of Electronic Publication: 2023 Aug 31.
DOI: 10.1002/mnfr.202200496
Abstrakt: Scope: The present study aims to assess the protective effect of Lactobacillus johnsonii JNU3402 (LJ3402) against diet-induced non-alcoholic fatty liver disease (NAFLD) and determine the mechanism underlying its beneficial effect on the liver in mice.
Methods and Results: Seven-week-old male mice are fed a high-fat diet (HFD) with or without oral supplementation of LJ3402 for 14 weeks. In mice fed an HFD, LJ3402 administration alleviates liver steatosis, diet-induced obesity, and insulin resistance with a decreased hepatic expression of sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), and an increased phosphorylation of SREBP-1c. The mechanistic study shows that LJ3402 inhibits SREBP-1c transcriptional activity by enhancing protein kinase A (PKA)-mediated phosphorylation and reduces the expression of its lipogenic target genes in AML12 and HepG2 cells, thereby attenuating hepatic lipid accumulation. Moreover, silencing the PKA α catalytic subunit or the inhibition of PKA activity by H89 abolishes LJ3402 suppression of free fatty acid (FFA)-induced SREBP-1c activity in hepatocytes. In addition, LJ3402 administration elevates the plasma lactate levels in mice fed an HFD; this lactate increases PKA-mediated SREBP-1c phosphorylation in AML12 cells with a decreased expression of its target genes, reducing hepatic lipid accumulation.
Conclusion: LJ3402 attenuates HFD-induced fatty liver in mice through the lactate-PKA-SREBP-1c pathway.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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