Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

JIANG SONGLING,UDDIN MD JAMAL,Xiaoying Yu,Lingjuan Piao,Dorotea Debra,Oh Goo Taeg,Ha Hunjoo 대한당뇨병학회 2022 Diabetes and Metabolism Journal Vol.46 No.6

Background: Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes. Peroxisomes are single membrane-enclosed organelles that play a role in the metabolism of lipid and reactive oxygen species. The present study examined the role of peroxisomes in high-fat diet (HFD)-induced NAFLD using fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist.Methods: Eight-week-old male C57BL/6J mice were fed either a normal diet or HFD for 12 weeks, and fenofibrate (50 mg/kg/day) was orally administered along with the initiation of HFD.Results: HFD-induced liver injury as measured by increased alanine aminotransferase, inflammation, oxidative stress, and lipid accumulation was effectively prevented by fenofibrate. Fenofibrate significantly increased the expression of peroxisomal genes and proteins involved in peroxisomal biogenesis and function. HFD-induced attenuation of peroxisomal fatty acid oxidation was also significantly restored by fenofibrate, demonstrating the functional significance of peroxisomal fatty acid oxidation. In <i>Ppara</i> deficient mice, fenofibrate failed to maintain peroxisomal biogenesis and function in HFD-induced liver injury.Conclusion: The present data highlight the importance of PPARα-mediated peroxisomal fitness in the protective effect of fenofibrate against NAFLD.

Acid Response of Bifidobacterium longum subsp. longum BBMN68 Is Accompanied by Modification of the Cell Membrane Fatty Acid Composition

( Songling Liu ),( Fazheng Ren ),( Jingli Jiang ),( Liang Zhao ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.6

The acid response of Bifidobacterium longum subsp. longum BBMN68 has been studied in our previous study. The fab gene, which is supposed to be involved in membrane fatty acid biosynthesis, was demonstrated to be induced in acid response. In order to investigate the relationship between acid response and cell membrane fatty acid composition, the acid adaptation of BBMN68 was assessed and the membrane fatty acid composition at different adaptation conditions was identified. Indeed, the fatty acid composition was influenced by acid adaptation. Our results showed that the effective acid adaptations were accompanied with decrease in the unsaturated to saturated fatty acids ratio (UFA/SFA) and increase in cyclopropane fatty acid (CFA) content, which corresponded to previous studies. Moreover, both effective and non-effective acid adaptation conditions resulted in decrease in the C18:1 cis- 9/C18:1 trans-9 ratio, indicating that the C18:1 cis-9/C18:1 trans-9 ratio is associated with acid tolerance response but not with acid adaptation response. Taken together, this study indicated that the UFA/SFA and CFA content of BBMN68 were involved in acid adaptation and the C18:1 cis-9/C18:1 trans-9 ratio was involved in acid tolerance response.

Bioactive Compounds / Food Microbiology : Enhanced Acid Tolerance in Bifidobacterium longum by Adaptive Evolution: Comparison of the Genes between the Acid-Resistant Variant and Wild-Type Strain

( Yunyun Jiang ),( Fazheng Ren ),( Songling Liu ),( Liang Zhao ),( Huiyuan Guo ),( Caiyun Hou ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.3

Acid stress can affect the viability of probiotics, especially Bifidobacterium. This study aimed to improve the acid tolerance of Bifidobacterium longum BBMN68 using adaptive evolution. The stress response, and genomic differences of the parental strain and the variant strain were compared by acid stress. The highest acid-resistant mutant strain (BBMN68m) was isolated from more than 100 asexual lines, which were adaptive to the acid stress for 10th, 20th, 30th, 40th, and 50th repeats, respectively. The variant strain showed a significant increase in acid tolerance under conditions of pH 2.5 for 2 h (from 7.92 to 4.44 log CFU/ml) compared with the wildtype strain (WT, from 7.87 to 0 log CFU/ml). The surface of the variant strain was also smoother. Comparative whole-genome analysis showed that the galactosyl transferase D gene (cpsD, bbmn68_1012), a key gene involved in exopolysaccharide (EPS) synthesis, was altered by two nucleotides in the mutant, causing alteration in amino acids, pI (from 8.94 to 9.19), and predicted protein structure. Meanwhile, cpsD expression and EPS production were also reduced in the variant strain (p < 0.05) compared with WT, and the exogenous WT-EPS in the variant strain reduced its acid-resistant ability. These results suggested EPS was related to acid responses of BBMN68.

Acid Response of Bifidobacterium longum subsp. longum BBMN68 Is Accompanied by Modification of the Cell Membrane Fatty Acid Composition

Liu, Songling,Ren, Fazheng,Jiang, Jingli,Zhao, Liang The Korean Society for Microbiology and Biotechnol 2016 Journal of microbiology and biotechnology Vol.26 No.7

The acid response of Bifidobacterium longum subsp. longum BBMN68 has been studied in our previous study. The fab gene, which is supposed to be involved in membrane fatty acid biosynthesis, was demonstrated to be induced in acid response. In order to investigate the relationship between acid response and cell membrane fatty acid composition, the acid adaptation of BBMN68 was assessed and the membrane fatty acid composition at different adaptation conditions was identified. Indeed, the fatty acid composition was influenced by acid adaptation. Our results showed that the effective acid adaptations were accompanied with decrease in the unsaturated to saturated fatty acids ratio (UFA/SFA) and increase in cyclopropane fatty acid (CFA) content, which corresponded to previous studies. Moreover, both effective and non-effective acid adaptation conditions resulted in decrease in the C_18:1 cis-9/C_18:1 trans-9 ratio, indicating that the C_18:1 cis-9/C_18:1 trans-9 ratio is associated with acid tolerance response but not with acid adaptation response. Taken together, this study indicated that the UFA/SFA and CFA content of BBMN68 were involved in acid adaptation and the C_18:1 cis-9/C_18:1 trans-9 ratio was involved in acid tolerance response.

Pan-Src kinase inhibitor treatment attenuates diabetic kidney injury via inhibition of Fyn kinase-mediated endoplasmic reticulum stress

Dorotea Debra,Jiang Songling,Pak Eun Seon,Son Jung Beom,Choi Hwan Geun,Ahn Sung-Min,Ha Hunjoo 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Src family kinases (SFKs) have been implicated in the pathogenesis of kidney fibrosis. However, the specific mechanism by which SFKs contribute to the progression of diabetic kidney disease (DKD) remains unclear. Our preliminary transcriptome analysis suggested that SFK expression was increased in diabetic kidneys and that the expression of Fyn (a member of the SFKs), along with genes related to unfolded protein responses from the endoplasmic reticulum (ER) stress signaling pathway, was upregulated in the tubules of human diabetic kidneys. Thus, we examined whether SFK-induced ER stress is associated with DKD progression. Mouse proximal tubular (mProx24) cells were transfected with Fyn or Lyn siRNA and exposed to high glucose and palmitate (HG-Pal). Streptozotocin-induced diabetic rats were treated with KF-1607, a novel pan-Src kinase inhibitor (SKI) with low toxicity. The effect of KF-1607 was compared to that of losartan, a standard treatment for patients with DKD. Among the SFK family members, the Fyn and Lyn kinases were upregulated under diabetic stress. HG-Pal induced p70S6 kinase and JNK/CHOP signaling and promoted tubular injury. Fyn knockdown but not Lyn knockdown inhibited this detrimental signaling pathway. In addition, diabetic rats treated with KF-1607 showed improved kidney function and decreased ER stress, inflammation, and fibrosis compared with those treated with losartan. Collectively, these findings indicate that Fyn kinase is a specific member of the SFKs implicated in ER stress activation leading to proximal tubular injury in the diabetic milieu and that pan-SKI treatment attenuates kidney injury in diabetic rats. These data highlight Fyn kinase as a viable target for the development of therapeutic agents for DKD.

Peroxiredoxin 3 deficiency accelerates chronic kidney injury in mice through interactions between macrophages and tubular epithelial cells

Hwang, Inah,Uddin, Md Jamal,Lee, Gayoung,Jiang, Songling,Pak, Eun Seon,Ha, Hunjoo Elsevier 2019 FREE RADICAL BIOLOGY AND MEDICINE Vol.131 No.-

<P><B>Abstract</B></P> <P>Chronic kidney disease (CKD) has become epidemic worldwide. Mitochondrial reactive oxygen species (ROS)-induced oxidative stress is an important mediator of CKD, and Prx3 plays a critical role in maintenance of mitochondrial ROS. The present study examined the role of Prx3 in the context of fibrosis, a common feature of CKD, using Prx3 KO mice under obstructive and diabetic stress. Prx3 deficiency accelerated fibrosis and inflammation accompanied by mitochondrial oxidative stress in obstructed and diabetic kidneys as well as in proximal tubular epithelial (mProx) cells. In addition, Prx3 deficiency induced Raw264.7 macrophages activation, leading to upregulation of proinflammatory cytokines. Conditioned media from LPS-stimulated Prx3 deficient macrophages accelerated proinflammatory and profibrotic cytokines in mProx cells. Interestingly, Prx3 deficiency induced most inflammatory and fibrotic cytokines at basal condition in both tissues and cells. Taken together, these results demonstrate that Prx3 deficiency can accelerate CKD through interactions between macrophages and tubular epithelial cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prx3 deficiency accelerates chronic kidney diseases (CKD) in mice. </LI> <LI> Prx3 deficiency increases macrophages activation in CKD. </LI> <LI> Prx3 deficiency upregulates interactions between macrophages and epithelial cells. </LI> <LI> Prx3 deficiency increases mitochondrial ROS leading to kidney fibrosis. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>