Obesity represents a low-grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low-dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT). An adipose tissue-resident bacterium Sphingomonas paucimobilis is identified as a potential inhibitor on the activation of brown fat and browning of inguinal WAT, resulting in defective adaptive thermogenesis. Mechanically, LPS and S. paucimobilis inhibit the production and release of 15-HETE by suppressing its main metabolic enzyme 12 lipoxygenase (12-LOX) and 15- Hydroxyeicosatetraenoic acid (15-HETE) rescues the impaired thermogenesis. Interestingly, 15-HETE directly binds to AMP-activated protein kinase α (AMPKα) and elevates the phosphorylation of AMPK, leading to the activation of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation (OXPHOS) complexes. Further analysis with human obesity subjects reveals that individuals with high body mass index displayed lower 15-HETE levels. Taken together, this work improves the understanding of how chronic inflammation impairs adaptive thermogenesis and provides novel targets for alleviating obesity.
Yujia Zhou,Zhiming Li,Xinghui Xie,Xingtao Zhou,Jielun Hu,Shaoping Nie
Gellan is a microbial polysaccharide synthesized by Sphingomonas paucimobilis , and is widely utilized in the food and pharmaceutical industries, as well as in other fields. However, much remains unknown about the key genes involved in the gellan synthesis pathway. In this study, ultraviolet (UV) and atmospheric room temperature plasma (ARTP) were employed to induce mutations in S . paucimobilis ATCC31461 (Sp31461 NC), and ultimately resulting a high-yield mutant strain (Sp31461 UA) with a yield increase of 120 % from 3.6 g/L to 8.3 g/L. The growth curve, monosaccharide composition and molecular weight indicated that mutagenesis accelerated the growth of the strain, but did not affect gellan's basic physicochemical property. A combined analysis of transcriptomic and metabolomic demonstrated that the differentially expressed genes and metabolites resulting from mutations were primarily enriched in pathways related to energy metabolism, among which potential key genes such as pgi , clpB , ycaJ associated with gellan yield, were further verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and gene overexpression. Notably, the strain overexpression the pgi gene resulted in a 20 % increase in gellan yield compared to the Sp31461 UA strain, reaching 10.0 g/L. In summary, the energy metabolism pathway in S . paucimobilis is closely linked to gellan biosynthesis, and high-yield strains of gellan can be developed through mutagenesis breeding and the overexpression of key genes identified by transcriptomics and metabolomics. This research offers valuable scientific insights for the industrial production and application of gellan.
危险品化学品经营许可证（带存储）