Anti-obesity potential of heat-killed Lactiplantibacillus plantarum K8 in 3T3-L1 cells and high-fat diet mice.

Probiotics exert anti-obesity effects in high-fat diet (HFD) obese mice, but there are few studies on anti-obesity using heat-killed probiotics. Here, we investigated the effect of heat-killed Lactiplantibacillus plantarum K8 (K8HK) on the anti-differentiation of 3T3-L1 preadipocytes and on anti-obesity in HFD mice. K8HK decreased triglyceride (TG) accumulation in 3T3-L1 cells. Specifically, 1 × 109 CFU/mL K8HK showed the greatest anti-obesity effect, while the same concentration of live L. plantarum K8 (K8 Live) showed cytotoxicity. K8HK increased suppressor of cytokine signaling (SOCS)-1, which might affect the JAK2-STAT3 signaling pathway activated during differentiation. As a result, the levels of transcription factors of adipogenesis such as Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) decreased in K8HK-treated cells. We also observed a decrease in the lipogenic enzymes and fatty acid binding protein 4 (FABP4). In the mouse study, oral ingestion of K8 Live and K8HK showed weight reduction and decrease in blood TG content at 12 weeks of feeding. In addition, TG synthesis was suppressed in liver and adipose tissues, and genes related to fat metabolism were suppressed. This study suggests that K8HK could be a good material to prevent obesity by inhibiting adipogenesis genes related to fat metabolism.

Alleviation of LPS-Induced Inflammation and Septic Shock by Lactiplantibacillus plantarum K8 Lysates.

We previously showed that Lactiplantibacillus plantarum K8 and its cell wall components have immunoregulatory effects. In this study, we demonstrate that pre-treatment of L. plantarum K8 lysates reduced LPS-induced TNF-α production in THP-1 cells by down-regulating the early signals of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The down-regulation of signals may be caused by the induction of negative regulators involved in toll-like receptor (TLR)-mediated signaling. However, co-treatment with high concentrations of L. plantarum K8 lysates and lipopolysaccharide (LPS) activated the late signaling of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB pathways and resulted in the induction of absent in melanoma 2 (AIM2) inflammasome-mediated interleukin (IL)-1ß secretion. Intraperitoneal injection of L. plantarum K8 lysates in LPS-induced endotoxin shock mice alleviated mortality and reduced serum tumor-necrosis factor (TNF)-α, IL-1ß, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. In addition, the mRNA levels of TNF-α, IL-1ß, and IL-6 decreased in livers from mice injected with L. plantarum K8 followed by LPS. Hematoxylin and eosin (H&E) staining of the liver showed that the cell size was enlarged by LPS injection and slightly reduced by L. plantarum K8 lysate pre-injection followed by LPS injection. Macrophage infiltration of the liver also decreased in response to the combination injection compared with mice injected with only LPS. Taken together, our results show that although L. plantarum K8 lysates differentially regulated the production of LPS-induced inflammatory cytokines in THP-1 cells, the lysates inhibited overall inflammation in mice. Thus, this study suggests that L. plantarum K8 lysates could be developed as a substance that modulates immune homeostasis by regulating inflammation.