scholarly journals Lactiplantibacillus plantarum dfa1 Outperforms Enterococcus faecium dfa1 on Anti-Obesity in High Fat-Induced Obesity Mice Possibly through the Differences in Gut Dysbiosis Attenuation, despite the Similar Anti-Inflammatory Properties

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 80
Author(s):  
Thunnicha Ondee ◽  
Krit Pongpirul ◽  
Kantima Janchot ◽  
Suthicha Kanacharoen ◽  
Thanapat Lertmongkolaksorn ◽  
...  

Fat reduction and anti-inflammation are commonly claimed properties of probiotics. Lactiplantibacillus plantarum and Enterococcus faecium were tested in high fat-induced obesity mice and in vitro experiments. After 16 weeks of probiotics, L. plantarum dfa1 outperforms E. faecium dfa1 on the anti-obesity property as indicated by body weight, regional fat accumulation, serum cholesterol, inflammatory cytokines (in blood and colon tissue), and gut barrier defect (FITC-dextran assay). With fecal microbiome analysis, L. plantarum dfa1 but not E. faecium dfa1 reduced fecal abundance of pathogenic Proteobacteria without an alteration in total Gram-negative bacteria when compared with non-probiotics obese mice. With palmitic acid induction, the condition media from both probiotics similarly attenuated supernatant IL-8, improved enterocyte integrity and down-regulated cholesterol absorption-associated genes in Caco-2 cell (an enterocyte cell line) and reduced supernatant cytokines (TNF-α and IL-6) with normalization of cell energy status (extracellular flux analysis) in bone-marrow-derived macrophages. Due to the anti-inflammatory effect of the condition media of both probiotics on palmitic acid-activated enterocytes was neutralized by amylase, the active anti-inflammatory molecules might, partly, be exopolysaccharides. As L. plantarum dfa1 out-performed E. faecium dfa1 in anti-obesity property, possibly through the reduced fecal Proteobacteria, with a similar anti-inflammatory exopolysaccharide; L. plantarum is a potentially better option for anti-obesity than E. faecium.

Author(s):  
Thunnicha Ondee ◽  
Krit Pongpirul ◽  
Kantima Janchot ◽  
Suthicha Kanacharoen ◽  
Thanapat Lertmongkolaksorn ◽  
...  

Fat reduction and anti-inflammation are commonly claimed properties of probiotics. Lactobacillus plantarum and Enterococcus faecium were tested in high fat-induced obesity mice and in vitro experiments. After 16 weeks of probiotics, L. plantarum outperforms E. faecium on the anti-obesity property as indicated by body weight, regional fat accumulation, serum cholesterol, inflammatory cytokines (in blood and colon tissue), and gut barrier defect (FITC-dextran assay). With fecal microbiome analysis, L. plantarum but not E. faecium reduced fecal abundance of pathogenic Proteobacteria without an alteration in total Gram-negative bacteria when compared with non-probiotics obese mice. With palmitic acid induction, the condition media from both probiotics similarly attenuated supernatant IL-8, improved enterocyte integrity and down-regulated cholesterol absorption-associated genes in Caco-2 cell (an enterocyte cell line) and reduced supernatant cytokines (TNF-α and IL-6) with normalization of cell energy status (extracellular flux analysis) in bone-marrow-derived macrophages. Because the anti-inflammatory effect of the condition media of both probiotics on palmitic acid-activated enterocytes was neutralized by amylase, the active anti-inflammatory molecules might, partly, be exopolysaccharides. As L. plantarum out-performed E. faecium in anti-obesity property, possibly through the reduced fecal Proteobacteria, with a similar anti-inflammatory exopolysaccharide; L. plantarum is a potentially better option for anti-obesity than E. faecium.


2021 ◽  
pp. 1-17
Author(s):  
Cong Phi Dang ◽  
Jiraphorn Issara-Amphorn ◽  
Awirut Charoensappakit ◽  
Kanyarat Udompornpitak ◽  
Thansita Bhunyakarnjanarat ◽  
...  

Controlof immune responses through the immunometabolism interference is interesting for sepsis treatment. Then, expression of immunometabolism-associated genes and BAM15, a mitochondrial uncoupling agent, was explored in a proinflammatory model using lipopolysaccharide (LPS) injection. Accordingly, the decreased expression of mitochondrial uncoupling proteins was demonstrated by transcriptomic analysis on metabolism-associated genes in macrophages (RAW246.7) and by polymerase chain reaction in LPS-stimulated RAW246.7 and hepatocytes (Hepa 1–6). Pretreatment with BAM15 at 24 h prior to LPS in macrophages attenuated supernatant inflammatory cytokines (IL-6, TNF-α, and IL-10), downregulated genes of proinflammatory M1 polarization (iNOS and IL-1β), upregulated anti-inflammatory M2 polarization (Arg1 and FIZZ), and decreased cell energy status (extracellular flux analysis and ATP production). Likewise, BAM15 decreased expression of proinflammatory genes (IL-6, TNF-α, IL-10, and iNOS) and reduced cell energy in hepatocytes. In LPS-administered mice, BAM15 attenuated serum cytokines, organ injury (liver enzymes and serum creatinine), and tissue cytokines (livers and kidneys), in part, through the enhanced phosphorylated αAMPK, a sensor of ATP depletion with anti-inflammatory property, in the liver, and reduced inflammatory monocytes/macrophages (Ly6C +ve, CD11b +ve) in the liver as detected by Western blot and flow cytometry, respectively. In conclusion, a proof of concept for inflammation attenuation of BAM15 through metabolic interference-induced anti-inflammation on macrophages and hepatocytes was demonstrated as a new strategy of anti-inflammation in sepsis.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 449-449
Author(s):  
Patricia Perez ◽  
Desiree Wanders ◽  
Hannah Land ◽  
Kathryn Chiang ◽  
Rami Najjar ◽  
...  

Abstract Objectives Studies suggest that inflammation mediates the link between obesity and its comorbidities including type 2 diabetes and cardiovascular disease. Hence, there is a demand for effective alternative or complementary approaches to treat obesity-associated inflammation. The objective of this study was to determine whether consumption of blackberries (BL) and raspberries (RB) alone or in combination reduce obesity-induced inflammation. Methods In Vitro Study: RAW 264.7 macrophages were pretreated with either BL, RB, or BL + RB, each at a final concentration of 200 µg/mL for 2 h. LPS (1 ng/mL) was then added to the media for 16 h. mRNA expression of inflammatory cytokines was measured. In Vivo Study: Five-week-old mice were acclimated to a low-fat low-sucrose (LFLS) diet for one week after which mice were randomized 10 per group to one of five groups: 1) LFLS, 2) high-fat high-sucrose (HFHS), 3) HFHS + 10% BL, 4) HFHS + 10% RB, or 5) HFHS + 5% BL + 5% RB. Expression of inflammatory markers was measured in the liver as well as epididymal and inguinal white adipose tissue. Results In Vitro Study: Each berry alone and in combination suppressed the LPS-induced increase in inflammatory markers, with the combination (BL + RB) having the greatest effect. The combination suppressed LPS-induced expression of Ccl2, Tnfa, F4/80, and Il6 by 3.7−, 5.3−, 5.3−, and 4.4-fold, respectively. In Vivo Study: Gene expression analysis indicated that berry consumption had no significant effect on proinflammatory (Ccl2, Il1b, Tnfa, Il6, Itgam) or anti-inflammatory (Adipoq, Arg1, Mgl1) markers in adipose tissue depots or liver. However, relatively low gene expression of inflammatory markers in the tissues indicates that the mice fed the HFHS diet failed to develop a robust inflammatory state. Conclusions BL and RB have direct anti-inflammatory effects on immune cells. Initial analysis indicates that consumption of BL and RB has no significant effects on markers of inflammation in a diet-induced mouse model of obesity. However, it is possible that the relatively low levels of inflammation in these mice masked the anti-inflammatory potential of BL and RB. Ongoing analysis will provide additional insights into the effects of BL and RB on inflammation in these tissues. Funding Sources Lewis Foundation Award.


Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2406 ◽  
Author(s):  
Andrey V. Markov ◽  
Aleksandra V. Sen’kova ◽  
Oksana V. Salomatina ◽  
Evgeniya B. Logashenko ◽  
Dina V. Korchagina ◽  
...  

Semi-synthetic triterpenoids, bearing cyano enone functionality in ring A, are considered to be novel promising therapeutic agents with complex inhibitory effects on tissue damage, inflammation and tumor growth. Previously, we showed that the cyano enone-containing 18βH-glycyrrhetinic acid derivative soloxolone methyl (SM) effectively suppressed the inflammatory response of macrophages in vitro and the development of influenza A-induced pneumonia and phlogogen-stimulated paw edema in vivo. In this work, we reported the synthesis of a novel 18βH-glycyrrhetinic acid derivative trioxolone methyl (TM), bearing a 2-cyano-3-oxo-1(2)-en moiety in ring A and a 12,19-dioxo-9(11),13(18)-dien moiety in rings C, D, and E. TM exhibited a high inhibitory effect on nitric oxide (II) production by lipopolysaccharide-stimulated J774 macrophages in vitro and dextran sulfate sodium (DSS)-induced colitis in mice, displaying higher anti-inflammatory activity in comparison with SM. TM effectively suppressed the DSS-induced epithelial damage and inflammatory infiltration of colon tissue, the hyperproduction of colonic neutral mucin and TNFα and increased glutathione synthesis. Our in silico analysis showed that Akt1, STAT3 and dopamine receptor D2 can be considered as mediators of the anti-colitic activity of TM. Our findings provided valuable information for a better understanding of the anti-inflammatory activity of cyano enone-bearing triterpenoids and revealed TM as a promising anti-inflammatory candidate.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81413 ◽  
Author(s):  
Ulrikke Voss ◽  
Elin Sand ◽  
Björn Olde ◽  
Eva Ekblad

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Chang-Won Cho ◽  
Sungeun Ahn ◽  
Tae-Gyu Lim ◽  
Hee-Do Hong ◽  
Young Kyoung Rhee ◽  
...  

We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium- (DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the pathological characteristics of colitis and significantly reduced production of proinflammatory cytokines in the serum. Histological analysis indicated that HMFO improved the signs of histological damage such as abnormal crypts, crypt loss, and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E2, nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. HMFO attenuated inflammation both in vitro and in vivo, primarily by inhibiting NF-κB activation. Our findings indicate that HMFO is a promising remedy for treating inflammatory bowel diseases, such as colitis.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1238-1238
Author(s):  
Thunnicha Ondee ◽  
Krit Pongpirul ◽  
Asada Leelahavanichkul

Abstract Objectives To investigate the correlation between a single administration of Lactobacillus acidophilus 5 (LA5)–a potent lactic acid-producing bacterium previously been shown to attenuate obesity–vs microbiota alteration. Methods LA5 was administered daily together at 1 × 108 colonies forming unit with a high-fat diet (HFD) for 8 weeks in male C57BL/6 mice. Fecal samples with bowel tissues were collected to measure Lactobacillus spp. and Akkermansia spp. Gut permeability, lipid profiles, obesity-induced liver damage, and serum cytokines were also measured. In vitro experiment was conducted by using the HepG2 hepatocyte cell-line with palmitic acid and/or endotoxin. Results LA5 attenuated obesity in mice as demonstrated by weight reduction, regional fat accumulation, lipidemia, liver injury, gut permeability defect, endotoxemia, and serum cytokines. Unsurprisingly, LA5 improved these parameters and acidified fecal pH leads to the attenuation of fecal dysbiosis. The fecal microbiome analysis in obese mice with or without LA5 indicated; i) decreased Bacteroideles, ii) reduced total fecal Gram-negative bacterial burdens (the sources of gut LPS), iii) enhanced Firmicutes (Gram-positive bacteria with potential benefits) and iv) increased Verrucomycobia, especially Akkermansia muciniphila, a bacterium with the anti-obesity property. With LA5 administration, A. muciniphila in the colon were more than 2,000 folds higher than the regular diet mice as determined by 16S rRNA. Besides, LA5 produced anti-inflammatory molecules with a similar molecular weight to LPS that reduced cytokine production in LPS-activated HepG2 cells. Conclusions LA5 attenuated obesity through i) gut dysbiosis attenuation, partly through the promotion of A. muciniphila (probiotics with the difficulty in preparation processes), ii) reduced endotoxemia, and iii) possibly decreased liver injury by producing the anti-inflammatory molecules. Funding Sources This research was supported by Thailand Research Fund (RDG6150124), Thailand Government Fund (RSA6080023), the Program Management Unit for Human Resources & Institutional Development Research and Innovation-CU [Global Partnership B16F630071 and Flagship B05F630073], and Matching fund (RA-MF-12/62). TO was funded by Second Century Fund (C2F), Chulalongkorn University.


2021 ◽  
Author(s):  
Xv Han ◽  
Qingguang Chen ◽  
Yahua Liu ◽  
Junfei Xv ◽  
Hao Lu

Abstract Background:IMCLs are an important factor in skeletal muscle insulin resistance. This study aimed to explore the effect of Jianpi Qinghua formula (JPQHF) on IMCLs and its mechanism, as well as the relationship between IMCLs and other skeletal muscle insulin sensitivity factors, thereby elucidating the mechanism by which JPQHF improves insulin sensitivity.Methods: In an in vivo experiment, JPQHF and pioglitazone (PIO) were individually used to treat C57 mice with high-fat diet-induced obesity. In an in vitro experiment, JPQHF and rapamycin in serum were individually used to treat C2C12 cells induced with palmitic acid. The IMCLs of tissue and cells were subjected to oil red O staining. The RNA and protein expression of PPARγ, myogenin, mTORC1 and members of the PI3K/AKT pathway in skeletal muscle tissue and C2C12 cells was examined. Differences between the different intervention groups were determined.Results: IMCLs were significantly increased in mice with obesity induced by a high-fat diet and the C2C12 cell line treated with palmitic acid compared to the corresponding controls. mTORC1 phosphorylation and PPARγ levels were also increased, and AKT phosphorylation and myogenin levels were decreased. Intervention with JPQHF reversed the above changes. In addition, the PPARγ level in C2C12 cells was reduced after intervention with rapamycin, an inhibitor of mTORC1. However, AKT phosphorylation and myogenin levels did not recover after rapamycin intervention.Conclusion: IMCLs were significantly increased in obese C57 mice and palmitic acid-treated C2C12 cells. JPQHF reduced IMCLs both in vivo and in vitro. Mechanistically, this effect likely occurred through JPQHF-mediated inhibition of the overactivation of mTORC1 and a subsequent reduction in the expression of PPARγ. However, the function of JPQHF in elevating myogenin levels and the PI3K/AKT pathway may not be entirely dependent on mTORC1.


Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 30
Author(s):  
Jorge G. García ◽  
Carlos de Miguel ◽  
Fermín I. Milagro ◽  
Guillermo Zalba ◽  
Eduardo Ansorena

Obesity is a global health issue associated with the development of metabolic syndrome, which correlates with insulin resistance, altered lipid homeostasis, and other pathologies. One of the mechanisms involved in the development of these pathologies is the increased production of reactive oxygen species (ROS). One of the main producers of ROS is the family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, among which NOX5 is the most recently discovered member. The aim of the present work is to describe the effect of endothelial NOX5 expression on neighboring adipose tissue in obesity conditions by using two systems. An in vivo model based on NOX5 conditional knock-in mice fed with a high-fat diet and an in vitro model developed with 3T3-L1 adipocytes cultured with conditioned media of endothelial NOX5-expressing bEnd.3 cells, previously treated with glucose and palmitic acid. Endothelial NOX5 expression promoted the expression and activation of specific markers of thermogenesis and lipolysis in the mesenteric and epididymal fat of those mice fed with a high-fat diet. Additionally, the activation of these processes was derived from an increase in IL-6 production as a result of NOX5 activity. Accordingly, 3T3-L1 adipocytes treated with conditioned media of endothelial NOX5-expressing cells, presented higher expression of thermogenic and lipolytic genes. Moreover, endothelial NOX5-expressing bEnd.3 cells previously treated with glucose and palmitic acid also showed interleukin (IL-6) production. Finally, it seems that the increase in IL-6 stimulated the activation of markers of thermogenesis and lipolysis through phosphorylation of STAT3 and AMPK, respectively. In conclusion, in response to obesogenic conditions, endothelial NOX5 activity could promote thermogenesis and lipolysis in the adipose tissue by regulating IL-6 production.


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