Oxyresveratrol Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats by Suppressing Inflammation.

Colitis causes destruction of the intestinal mucus layer and increases intestinal inflammation. The use of antioxidants and anti-inflammatory agents derived from natural sources has been recently highlighted as a new approach for the treatment of colitis. Oxyresveratrol (OXY) is an antioxidant known to have various beneficial effects on human health, such as anti-inflammatory, antibacterial activity, and antiviral activity. The aim of this study was to investigate the therapeutic effect of OXY in rats with dextran sulfate sodium (DSS)-induced acute colitis. OXY ameliorated DSS-induced colitis and repaired damaged intestinal mucosa. OXY downregulated the expression of pro-inflammatory cytokine genes (TNF-α, IL-6, and IL-1ß) and chemokine gene MCP-1, while promoting the production of anti-inflammatory cytokine IL-10. OXY treatment also suppressed inflammation via inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in the colon, as well as the activity of myeloperoxidase (MPO). OXY exhibited anti-apoptotic effects, shifting the Bax/Bcl-2 balance. In conclusion, OXY might improve DSS-induced colitis by restoring the intestinal mucus layer and reducing inflammation within the intestine.

An oral toxicity test in rats and a genotoxicity study of extracts from the stems of Opuntia ficus-indica var. saboten.

BACKGROUND: Opuntia ficus-indica var. saboten (OFIS) is used widely in Korea to treat constipation due to its diuretic effects and its enhancement of bowel function and appetite. However, its safety has not yet been established. The aim of this study was to evaluate the repeated oral toxicity and genotoxicity of OFIS extract (OE). METHODS: White female and male Sprague Dawley rats (n = 6) were divided into 4 groups, and OE was administered to them orally (0, 500, 1000, and 2000 mg/kg/day, respectively) for one week. The Ames test, the chromosomal aberration assay, and the mammalian micronucleus test were performed to determine the OE genotoxicity. The Ames test was conducted using Salmonella typhimurium (S. typhimurium) strains TA100, TA1535, TA98, and TA153 and Escherichia coli (E. coli) WP2 urvA, and Chinese hamster lung (CHL) cells were used for the chromosomal aberration assay. The mammalian micronucleus test was performed using mouse bone marrow cells. RESULTS: This study revealed that OE administration did not alter the normal rat behavior, body weight gain, and food and water consumption with respect to the normal controls. In addition, there were no toxic effects observed during the ophthalmological test. The biochemical hematological and serum values as well as urinalysis parameters and organ weights were all similar to those of the normal control group. In addition, no mutagenicity effects from the OE were found in S. typhimurium or E. coli with or without S9 activation according to the Ames test. The OE did not significantly alter the number of structural aberrations in the CHL cells in the presence or absence of S9 activation. The oral administration of OE also caused no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes. CONCLUSIONS: In conclusion, OE could be considered as a reliable and safe herbal medicine or functional food since no toxicity was found under the conditions of this study.

Lifespan Extension of Caenorhabditis elegans by Butyricicoccus pullicaecorum and Megasphaera elsdenii with Probiotic Potential.

Butyricicoccus pullicaecorum and Megasphaera elsdenii inhabit the human intestine and have probiotic potential. The aim of this study was to evaluate the effects of B. pullicaecorum and M. elsdenii on the lifespan of Caenorhabditis elegans. They significantly (P < 0.05) extended the lifespan of C. elegans compared with Escherichia coli OP50, a standard food for the worm. Analysis of age-related biomarkers such as lipofuscin, body size, and locomotory activity showed that they retarded aging. They all failed to extend the lifespan of daf-12 or dbl-1 loss-of-function C. elegans mutants compared with E. coli OP50-fed worms. However, the increase in lifespan was observed in daf-16, jnk-1, pmk-1, and skn-1 mutants. Moreover, they increased the resistance of C. elegans to a human pathogen, Salmonella typhimurium. In conclusion, B. pullicaecorum and M. elsdenii extend the lifespan of C. elegans via the transforming growth factor-beta (TGF-ß) pathway associated with anti-inflammatory processes in the innate immune system.

Bee Venom Promotes Hair Growth in Association with Inhibiting 5α-Reductase Expression.

Alopecia is an important issue that can occur in people of all ages. Recent studies show that bee venom can be used to treat certain diseases including rheumatoid arthritis, neuralgia, and multiple sclerosis. In this study, we investigated the preventive effect of bee venom on alopecia, which was measured by applying bee venom (0.001, 0.005, 0.01%) or minoxidil (2%) as a positive control to the dorsal skin of female C57BL/6 mice for 19 d. Growth factors responsible for hair growth were analyzed by quantitative real-time PCR and Western blot analysis using mice skins and human dermal papilla cells (hDPCs). Bee venom promoted hair growth and inhibited transition from the anagen to catagen phase. In both anagen phase mice and dexamethasone-induced catagen phase mice, hair growth was increased dose dependently compared with controls. Bee venom inhibited the expression of SRD5A2, which encodes a type II 5α-reductase that plays a major role in the conversion of testosterone into dihydrotestosterone. Moreover, bee venom stimulated proliferation of hDPCs and several growth factors (insulin-like growth factor 1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)2 and 7) in bee venom-treated hDPCs dose dependently compared with the control group. In conclusion, bee venom is a potentially potent 5α-reductase inhibitor and hair growth promoter.

An ethanol extract of Ramulus mori improves blood circulation by inhibiting platelet aggregation.

Inappropriate platelet aggregation can cause blood coagulation and thrombosis. In this study, the effect of an ethanol extract of Ramulus mori (ERM) on blood circulation was investigated. The antithrombotic activity of ERM on rat carotid arterial thrombosis was evaluated in vivo, and the effect of ERM on platelet aggregation and blood coagulation time was evaluated ex vivo. To evaluate the safety of ERM, its cytotoxicity to platelets and its effect on tail bleeding time were assessed; ERM was not toxic to rat platelets and did not prolong bleeding time. Moreover, administering ERM to rats had a significant preventive effect on carotid arterial thrombosis in vivo, and significantly inhibited adenosine diphosphate- and collagen-induced platelet aggregation ex vivo, whereas it did not prolong coagulation periods, such as prothrombin time and activated partial thromboplastin time. The results suggest that ERM is effective in improving blood circulation via antiplatelet activity rather than anticoagulation activity.

Antihyperlipidemic effects of rhapontin and rhapontigenin from rheum undulatum in rats fed a high-cholesterol diet.

Rhapontin was purified from a methanol extract from the roots of Rheum undulatum, and rhapontigenin was produced by an enzymatic transformation of rhapontin. Rats were fed a high-cholesterol diet to induce hyperlipidemia, followed by oral treatment with rhapontin or rhapontigenin (1-5 mg/kg/day). Rhapontin and rhapontigenin treatment resulted in a significant (p<0.05) dose-dependent decrease in the serum lipid level, while the high-density lipoprotein cholesterol level increased slightly compared with the experimental control. Furthermore, rhapontin and rhapontigenin treatment improved the pathological characteristics of the degenerating fatty liver in high-cholesterol diet-induced hyperlipidemic rats dose-dependently. Aspartate aminotransferase and alanine aminotransferase levels in rhapontin- and rhapontigenin-treated hyperlipidemic rats were not significantly different from those in the control. These results indicate that rhapontin and rhapontigenin can be used as potent antihyperlipidemic agents.

Protective Effects of Heat-Killed Ruminococcus albus against ß-Amyloid-Induced Apoptosis on SH-SY5Y Cells.

A high level of ß-amyloid (Aß) in the brains of patients with Alzheimer's disease (AD) generates reactive oxygen species that induce neuronal death and DNA damage. The interaction between the gut microbiota and brain health has attracted attention in recent years. Heat-killed Ruminococcus albus (hkRA) reportedly protects neurons against damage induced by oxidative stress. However, whether hkRA can inhibit Aß-induced apoptosis and thus alleviate AD remains unclear. Hence, we aimed to evaluate the protective effects of hkRA against Aß-induced apoptosis on the human neuroblastoma SH-SY5Y cell. HkRA treatment (108 cells/ml) significantly decreased the Aß-induced cytotoxicity and DNA damage in the SH-SY5Y cells. It also showed a significant increase of the bax/bcl-2 ratio in the Aß-treated SH-SY5Y cells. Moreover, hkRA treatment stimulated the expression of antioxidation-related genes HO-1, Nrf2, and PKC-δ and increased the expression of brain-derived neurotrophic factor (BDNF). Meanwhile, it significantly decreased the activity of caspase-3 and protein expression of cleaved caspase-3 in the Aß-treated SH-SY5Y cells. Additionally, the protein levels of mitochondrial and cytosolic cytochrome c increased and decreased, respectively, in the cells. These results suggest that hkRA protects human neuroblastoma cells from Aß-induced apoptosis and oxidative stress. Thus, hkRA may be developed into a health-promoting paraprobiotic (the inactivated microbial cells of probiotics) for patients with AD.

Microbial chaperonin 60 inhibits osteoclast differentiation by interfering with RANK/RANKL binding and overexpression of lipocalin2.

Osteoclasts play a crucial role in bone destruction in rheumatoid arthritis (RA). This study aimed to investigate the inhibitory effects of chaperonin 60 (CPN60), identified in the surface proteins of Propionibacterium freudenreichii MJ2, on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation, and elucidate the underlying mechanisms. Treatment with CPN60 inhibited RANKL-induced osteoclast differentiation by decreasing the expression of osteoclast differentiation-related genes and proteins. CPN60 interfered with the binding of RANKL to RANK, as elucidated using surface plasmon resonance (SPR) and immunofluorescence. In silico molecular docking analysis further supported the interference of CPN60 with the binding of RANKL and RANK. CPN60 suppressed the expression of molecules linked to the calcium-dependent pathway in RANKL-induced osteoclast differentiation at both mRNA and protein levels. Microarray analysis showed elevated expression of lipocalin 2 (Lcn2), which was closely linked to the inhibition of osteoclast differentiation in CPN60-treated RAW 264.7 cells. Inhibition of Lcn2 decreased the inhibitory effect of CPN60 on osteoclast differentiation, indicating that increased expression of Lcn2 by CPN60 contributes to the inhibition of osteoclastogenesis. In addition, CPN60 treatment alleviated arthritis symptoms in collagen-induced arthritis mice by reducing the generation of collagen-specific antibodies and inhibiting osteoclast differentiation. In conclusion, CPN60 of P. freudenreichii MJ2 interfered with RANKL-RANK binding, reduced the expression of genes and proteins related to osteoclast differentiation and upregulated Lcn2 expression, thereby inhibiting RANKL-induced osteoclast differentiation, which might contribute to ameliorate collagen-induced arthritis.

The possible mechanism of rhapontigenin influencing antifungal activity on Candida albicans.

Rhapontigenin, an aglycone of rhapontin, was produced by biotransformation and we investigated its antifungal activity against Candida albicans, one of the most important opportunistic fungal pathogens. Rhapontigenin is found to have, in vitro, inhibitory activity with a minimal inhibitory concentration (MIC) value against all test isolates of 128-256 µg/ml. We detected increased reactive oxygen species (ROS) levels in yeast cultures treated with rhapontigenin at the MIC. Rhapontigenin inhibited DNA, RNA, and protein synthesis, especially RNA synthesis, and induced morphological changes and apoptosis of C. albicans. The apoptotic effect of rhapontigenin on C. albicans at subinhibitory concentrations was higher in the stationary growth phase than in the exponential phase, while the opposite results were noted with amphotericin B. The mechanism of antifungal activity of rhapontigenin may be associated with the generation of ROS that might induce apoptosis and it may also involve the inhibition of ergosterol biosynthesis.

High prevalence of amantadine-resistant influenza A virus isolated in Gyeonggi Province, South Korea, during 2005-2010.

Amantadine resistance among influenza A viruses was investigated in South Korea in 2005-2010. Of 308 influenza A viruses examined, 229 had the S31N substitution in the M2 protein. The frequency of amantadine resistance was 30 %, 100 %, and 76 % in influenza A/H1N1, pandemic A/H1N1 2009(A/H1N1pdm), and A/H3N2 subtypes, respectively. The amantadine-resistant influenza A/H1N1pdm and A/H3N2 viruses were circulating continuously from 2008 to 2009 and from 2005 to 2006, respectively. Amantadine resistance among influenza A viruses increased dramatically during the 5-year study period, and this has diminished the usefulness of this class of drugs.

Oseltamivir-resistant influenza viruses isolated in South Korea from 2005 to 2010.

South Korean isolates of oseltamivir-resistant influenza viruses from 2005-2010 were investigated with a total 491 influenza viruses identified from 1702 specimens. Neuraminidase genes from 342 influenza viruses (71 A/H1N1, 74 pandemic A/H1N1 2009, 117 A/H3N2, and 80 B) were analyzed by RT-PCR with molecular markers for oseltamivir resistance. The H274Y mutation in the NA protein was identified in 100 % (n=40) of A/H1N1 viruses circulating in 2008-2009. Influenza A/H1N1 viruses harboring the H274Y substitution exhibited, on average, a 626-fold reduction in oseltamivir susceptibility and clustered with the A/Norway/1736/2007 strain. Close and timely monitoring for resistance to clinically available influenza antivirals should be consistently performed.

Effect of water-soluble fraction of cherry tomatoes on the adhesion of probiotics and Salmonella to intestinal epithelial cells.

BACKGROUND: Tomato is one of the most consumed vegetables in the world and contains many valuable nutritional components. Here we investigate the prebiotic effects of cherry tomatoes for improving gut health. RESULTS: Water-soluble dietary fiber was prepared from fresh and processed (heat treatment at 80 °C for 15 min) cherry tomato samples, each with and without Viscozyme L treatment. In the adhesion assays, all water-soluble dietary fiber samples improved adhesion of probiotics (Lactobacillus rhamnosus and Bifidobacterium bifidum) to intestinal epithelial cells (Caco-2 cells). Heat treatment in the preparation of juice from cherry tomatoes showed no significant effect on the adhesion of probiotics to Caco-2 cells. The oligofructose content of samples affected the intestinal adhesion of probiotic bacteria, with higher oligosaccharide concentrations associated with greater adhesion of probiotics and more inhibition of the adhesion of pathogens to Caco-2 cells. CONCLUSION: The present results suggest that cherry tomato can act as a prebiotic, with oligofructose potentially being one of its major prebiotic components.

Surface-exposed chaperonin 60 derived from Propionibacterium freudenreichii MJ2 inhibits adipogenesis by decreasing the expression of C/EBPα/PPARγ.

Recent studies have shown that the health benefits of probiotics are not limited to those offered by living bacteria. It was reported that both live and killed cells of Propionibacterium freudenreichii MJ2 (MJ2) isolated from raw milk showed antiobesity activity in 3T3-L1 cells and high-fat diet-induced obese mice. This study was aimed at identifying the active component(s) responsible for the antiadipogenic activity of MJ2. Cell wall, surface protein, and cytoplasmic fractions of MJ2 were investigated for their inhibitory effects on adipogenesis in 3T3-L1 cells. Adipocytes treated with the surface protein fraction showed significantly lower lipid accumulation. Using the MASCOT algorithm following LC-MS/MS analysis, 131 surface proteins were identified and they were principally classified into three categories (network clusters related to ribosomes, carbon metabolism, and chaperones). Among them, chaperonin 60 (Cpn60) was selected as a potential candidate protein. Cpn60 inhibited lipid accumulation and adipogenesis during the early period of differentiation (days 0-2) and decreased expression of genes related to adipogenesis (Pparg and Cebpa) and lipogenesis (Fas and Scd1). The expression of Gata2/3, which suppresses adipogenesis, significantly increased in Cpn60-treated cells. Moreover, the nuclear translocation of C/EBPß was inhibited by Cpn60 treatment. In conclusion, Cpn60, a surface protein in MJ2, shows antiadipogenic activity by reducing the expression of C/EBPß through the upregulation of Gata2/3 expression followed by downregulation of Pparg and Cebpa expression.

Surface proteins of Propionibacterium freudenreichii MJ2 inhibit RANKL-induced osteoclast differentiation by lipocalin-2 upregulation and lipocalin-2-mediated NFATc1 inhibition.

Osteoclasts degrade bone and osteoclast differentiation has been implicated in bone destruction in rheumatoid arthritis. The dairy bacterium Propionibacterium freudenreichii MJ2 (MJ2) isolated from raw milk inhibits osteoclast differentiation and ameliorates collagen-induced arthritis. This study aimed to investigate the inhibitory effect of the surface proteins of MJ2 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and explain the underlying mechanism. The murine macrophage cell line RAW 264.7 was used to study the inhibition of osteoclast differentiation. The surface proteins significantly inhibited RANKL-induced osteoclast differentiation in a protein concentration-dependent manner by inhibiting the expression of genes and proteins related to osteoclast differentiation. RNA microarray analysis showed that the surface proteins significantly upregulated lipocalin-2 (lcn2) expression. In addition, they downregulated c-fos and NFATc1 and inhibited the expression of NFATc1-downstream genes Atp6v0d2, Calcr, and Ctsk. siRNA silencing of lcn2 decreased the extent of surface protein inhibition on osteoclast differentiation, suggesting that lcn2 plays an important role in the inhibition of RANKL-induced osteoclast differentiation. In conclusion, surface proteins of MJ2 show inhibitory effects on RANKL-induced osteoclast differentiation by upregulating lcn2 expression, in turn downregulating NFATc1, leading to the inhibition of NFATc1-downstream osteoclastogenesis-related gene expression.

Rhapontigenin converted from rhapontin purified from Rheum undulatum enhances the inhibition of melanin synthesis.

Rhapontigenin was produced from rhapontin isolated from a methanol extract of Rheum undulatum roots by enzymatic transformation. Rhapontin and rhapontigenin exhibited dose-dependent inhibition of tyrosinase activity and melanin synthesis in B16F10 melanoma cells, but the inhibitory activity of rhapontigenin was greater than that of rhapontin. Thus the bioconversion of rhapontin enhanced its ability to inhibit cellular tyrosinase activity and melanin synthesis.

Evaluation of the inhibition of mushroom tyrosinase and cellular tyrosinase activities of oxyresveratrol: comparison with mulberroside A.

The inhibitory effects of oxyresveratrol, the aglycone of mulberroside A, on mushroom and cellular tyrosinase activities and melanin synthesis were evaluated. Mulberroside A and oxyresveratrol showed inhibitory activity against mushroom tyrosinase, with oxyresveratrol demonstrating a greater inhibitory effect than that of mulberroside A. Oxyresveratrol and mulberroside A strongly inhibited melanin production in Streptomyces bikiniensis and exhibited dose-dependent inhibition of tyrosinase activity and inhibition of melanin synthesis in B16F10 melanoma cells. However, the compounds exhibited nearly similar inhibitory effects on the activity of cellular tyrosinase and melanin synthesis in murine melanocytes. The inhibition of melanin synthesis by mulberroside A and oxyresveratrol was involved in suppressing the expression level of melanogenic enzymes, tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). These results indicate that the inhibition rate of mushroom tyrosinase might not provide an accurate estimate of the inhibition rate of melanin synthesis in melanocytes.

Specific activation of hypoxia-inducible factor-2α by propionate metabolism via a ß-oxidation-like pathway stimulates MUC2 production in intestinal goblet cells.

Microbiota-derived short-chain fatty acids (SCFAs) are known to stimulate mucin expression in the intestine, which contributes to the gut mucosal immune responses, and the gut mucosal immune system extends to the brain and other organs through several axes. Hypoxia-inducible factors (HIFs), especially HIF-1α, are known to act as the master regulator of mucin expression, however, underlying mechanism of mucin expression during hypoxia by SCFAs remains unclear. In this study, we investigated the mechanism of MUC2 expression by propionate, an SCFA, in intestinal goblet cells. The real time oxygen consumption rate (OCR) and ATPase activity were measured to investigate the induction of hypoxia by propionate. Using 2-dimensional electrophoresis (2-DE), microarray analysis, and siRNA-induced gene silencing, we found that propionate is metabolized via a ß-oxidation-like pathway instead of the vitamin B12-dependent carboxylation pathway (also known as the methylmalonyl pathway). We verified the results by analyzing several intermediates in the pathway using LC-MS and GC-MS. Propionate metabolism via the ß-oxidation-like pathway leads to the depletion of oxygen and thereby induces hypoxia. Analysis of HIFs revealed that HIF-2α is the primary HIF whose activation is induced by propionate metabolism in a hypoxic environment and that HIF-2α regulates the expression of MUC2. Thus, hypoxia induced during propionate metabolism via a ß-oxidation-like pathway specifically activates HIF-2α, stimulating MUC2 production in LS 174 T goblet cells. Our findings show that propionate-induced selective HIF-2α stimulation contributes to intestinal mucosal defense.

Remofuscin induces xenobiotic detoxification via a lysosome-to-nucleus signaling pathway to extend the Caenorhabditis elegans lifespan.

Lipofuscin is a representative biomarker of aging that is generated naturally over time. Remofuscin (soraprazan) improves age-related eye diseases by removing lipofuscin from retinal pigment epithelium (RPE) cells. In this study, the effect of remofuscin on longevity in Caenorhabditis elegans and the underlying mechanism were investigated. The results showed that remofuscin significantly (p < 0.05) extended the lifespan of C. elegans (N2) compared with the negative control. Aging biomarkers were improved in remofuscin-treated worms. The expression levels of genes related to lysosomes (lipl-1 and lbp-8), a nuclear hormone receptor (nhr-234), fatty acid beta-oxidation (ech-9), and xenobiotic detoxification (cyp-34A1, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A4, cyp-35A5, cyp-35C1, gst-28, and gst-5) were increased in remofuscin-treated worms. Moreover, remofuscin failed to extend the lives of C. elegans with loss-of-function mutations (lipl-1, lbp-8, nhr-234, nhr-49, nhr-8, cyp-35A1, cyp-35A2, cyp-35A3, cyp-35A5, and gst-5), suggesting that these genes are associated with lifespan extension in remofuscin-treated C. elegans. In conclusion, remofuscin activates the lysosome-to-nucleus pathway in C. elegans, thereby increasing the expression levels of xenobiotic detoxification genes resulted in extending their lifespan.

Probiotic Propionibacterium freudenreichii MJ2 Enhances Osteoblast Differentiation and Mineralization by Increasing the OPG/RANKL Ratio.

Osteoblast differentiation is important for the development of bone and the maintenance of bone density. Propionibacterium freudenreichii is a probiotic with an anti-inflammatory property. The aim of this study was to investigate the enhancement effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoblast differentiation, mineralization, and its signaling pathway. For in vitro and in vivo experiments, human fetal osteoblastic cell line hFOB 1.19 and an ovariectomized rat model were used, respectively. Expression levels of genes and proteins related to osteoblast differentiation and mineralization were measured by real-time polymerase chain reaction (qPCR) and Western blotting, respectively. Alizarin red S staining was performed to measure osteoblast mineralization. Heat-killed MJ2 (hkMJ2)-treated cells showed significantly increased osteoblast differentiation via an increase in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) ratio and significantly increased osteoblast mineralization by stimulating the expression of bone morphogenetic protein 2 and runt-related transcription factor 2. Additionally, oral administration of live or heat-killed MJ2 to ovariectomized rats inhibited osteoporosis-induced bone loss. Specifically, surface proteins isolated from MJ2 promoted osteoblast differentiation and mineralization. In conclusion, MJ2 enhanced osteoblast differentiation and mineralization through the OPG/RANKL signaling pathway and the effective component of MJ2 might be its surface proteins.

Antiobesity and antidiabetic effects of the dairy bacterium Propionibacterium freudenreichii MJ2 in high-fat diet-induced obese mice by modulating lipid metabolism.

Obesity can cause chronic metabolic disorders such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver diseases. The aim of this study was to investigate the antiobesity and antidiabetic effects of the dairy bacterium P. freudenreichii MJ2 isolated from raw milk using 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. Lipid accumulation and the expression levels of genes related to lipid metabolism, such as preadipocytic gene (Pref-1), adipogenic genes (PPARγ and C/EBPα), and lipogenic genes (FAS, SCD-1, and ACC), significantly decreased in heat-killed P. freudenreichii MJ2 (hkMJ2)-treated adipocytes. Live P. freudenreichii MJ2 (MJ2), hkMJ2, and Lactobacillus plantarum (LP) decreased body weight gain in HFD-induced obese mice compared with the model group. The liver and epididymal white adipose tissue weights in the MJ2-, hkMJ2- and LP-treated groups were significantly lower than those in the model group. The expression levels of genes and proteins related to adipogenesis and lipogenesis significantly decreased and lipolysis (HSL and ATGL) increased in the MJ2-, hkMJ2-, and LP-treated groups. The expression levels of genes related to fatty acid ß-oxidation (CPT-1α and ACOX1) increased in the MJ2-, hkMJ2-, and LP-treated groups. In addition, blood glucose and fasting insulin levels in the MJ2- and hkMJ2-treated groups decreased compared with those in the model group. P. freudenreichii MJ2 ameliorate insulin resistance by obesity. In conclusion, both MJ2 and hkMJ2 alleviate obesity and metabolic syndrome.