Hypothalamic-hindbrain circuit for consumption-induced fear regulation.

To ensure survival, animals must sometimes suppress fear responses triggered by potential threats during feeding. However, the mechanisms underlying this process remain poorly understood. In the current study, we demonstrated that when fear-conditioned stimuli (CS) were presented during food consumption, a neural projection from lateral hypothalamic (LH) GAD2 neurons to nucleus incertus (NI) relaxin-3 (RLN3)-expressing neurons was activated, leading to a reduction in CS-induced freezing behavior in male mice. LHGAD2 neurons established excitatory connections with the NI. The activity of this neural circuit, including NIRLN3 neurons, attenuated CS-induced freezing responses during food consumption. Additionally, the lateral mammillary nucleus (LM), which received NIRLN3 projections, along with RLN3 signaling in the LM, mediated the decrease in freezing behavior. Collectively, this study identified an LHGAD2-NIRLN3-LM circuit involved in modulating fear responses during feeding, thereby enhancing our understanding of how animals coordinate nutrient intake with threat avoidance.

Fermented natto powder alleviates obesity by regulating LXR pathway and gut microbiota in obesity rats.

AIM: This study aimed to investigate the positive effect of natto powder on obese rats fed with a high-fat diet (HFD). METHODS AND RESULTS: Sprague-Dawley rats were fed with a HFD for 8 weeks continuously and gavaged with natto powder, respectively, for 8 weeks starting from the ninth week. The results showed that natto powder significantly reduced the body weight of rats and maintained the balance of cholesterol metabolism in the body by inhibiting the activity of liver X receptors (LXR) target genes, increasing the active expression of cholesterol 7 alpha-hydroxylase, and reducing the active expression of sterol-regulatory element-binding protein and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Furthermore, natto powder increased the relative abundance of potentially beneficial microbiota in gut and decreased the relative abundance of obesity-related harmful bacteria, and also increased the Bacteroidetes/Firmicutes ratio and improved the composition of gut microbiota. CONCLUSIONS: Natto powder maintains the balance of cholesterol metabolism by inhibiting the LXR pathway and regulating the gut microbiota.

Effects of Bacillus subtilis natto JLCC513 on gut microbiota and intestinal barrier function in obese rats.

AIMS: This study aimed to investigate the effects of Bacillus subtilis natto JLCC513 (JLCC513) on gut microbiota, inflammation and intestinal barrier function in high-fat-diet (HFD) rats. METHODS AND RESULTS: Sprague-Dawley (SD) rats were fed HFD for 16 weeks, and treated with JLCC513 in 9th week. The oral administration of JLCC513 decreased body weight and reduced the inflammation level in HFD rats. Pathologically, JLCC513 prevented the detachment of ileal villus and increased the villus height in rats. Mechanistically, western blot analysis showed that the protein levels of tight junction (TJ) proteins involved in intestinal barrier function, including zonula occludens-1 (ZO-1), occludin and claudin-1, were increased after JLCC513 treatment. Meanwhile, JLCC513 treatment also decreased the protein levels of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB) and NOD-like receptor protein 3 (NLRP3), indicating inhibition of the TLR4/NF-κB/NLRP3 pathway. Furthermore, faecal analysis showed that JLCC513 increased the abundance of Lactobacillus and Oscillospira and the ratio of Firmicutes/Bacteroidetes (F/B), and decreased the levels of Blautia and C_Clostridium. CONCLUSIONS: JLCC513 alleviated intestinal barrier dysfunction by inhibiting TLR4/NF-κB/NLRP3 pathway and regulating gut microbiota disorders. SIGNIFICANCE AND IMPACT OF STUDY: Our study might provide new treatment strategies for obesity and metabolic diseases.

Black bean husk and black rice anthocyanin extracts modulated gut microbiota and serum metabolites for improvement in type 2 diabetic rats.

Black rice and black bean have not yet been fully investigated as healthy foods for their therapeutic effects on type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the antidiabetic effects of black rice, black bean husk anthocyanin extracts, and their combination on glycolipid metabolism, gut microbiota, and serum metabolites in T2DM rats. Black bean husk and black rice anthocyanin extracts were administered to T2DM rats by gavage for 4 weeks. The results showed that black rice and black bean husk anthocyanin extracts significantly improved blood glucose, insulin resistance, serum oxidative stress state, lipid metabolism and inflammatory cytokines levels in rats, and alleviated liver damage. Black rice and black bean husk anthocyanin extracts increased the abundance of short-chain fatty acid (SCFA) producing bacteria Akkermansia spp., Phascolarctobacterium spp., Bacteroides spp., and Coprococcus spp., changed the gut microbiota structure; activated AMPK, PI3K, and AKT; inhibited HMGCR, G6pase and PEPCK expression; and inhibited hepatic gluconeogenesis. Moreover, by adjusting the levels of urea, deoxycytidine, L-citrulline, pseudouridine, and other serum metabolites in T2DM rats, the arginine biosynthesis and pyrimidine metabolism pathways were downregulated. The above results indicated that black rice and black bean husk anthocyanin extracts had a significant impact on the development of T2DM.

Bacillus natto ameliorates obesity by regulating PI3K/AKT pathways in rats.

Obesity has become the second leading cause of death globally after smoking. Probiotic Bacillus has noticeable weight-loss effects. This study aimed to investigate the mechanism of Bacillus natto (B. natto) on insulin resistance in obese rats. The obese rat model was established with a HFD for 8 weeks, and then, B. natto was orally administered at different dosed for 8 weeks. The results showed that B. natto significantly reduced the body weight, epididymis fat weight, total cholesterol, triglyceride, low-density lipoprotein while increasing the level of high-density lipoprotein in HFD rats. B. natto intervention improved liver injury by reducing alanine aminotransferase and aspartate transaminase levels. B. natto intervention was also beneficial for the inhibition of hepatic steatosis and inflammation factors in HFD rats by inhibiting the mRNA expression level of SREBP-1 gene. Moreover, B. natto improved insulin resistance homeostasis by activating PI3K/AKT signaling pathway. Therefore, B. natto could be used as a potential probiotic supplement to provided new strategy for the prevention and treatment of metabolic diseases such as obesity.