Daily Endocrinology Research Analysis

Adipocytes exhibit cellular plasticity by secreting pro-inflammatory cytokines in response to an energy excess. Here, we identify that interleukin (IL)-11 is robustly induced and secreted from adipocytes, especially beige adipocytes upon adrenergic stimulation. IL-11 inhibits adipocyte thermogenesis through binding to IL-11 receptor a (IL-11Ra) and serves as a "brake" to maintain energy homeostasis. Adipocyte-specific IL-11Ra-knockout mice exhibit enhanced whole-body energy consumption and improved glucose and lipid metabolism under a high-fat diet (HFD). Inhibition of IL-11/IL-11Ra signaling enhances sphingosine kinase 1 (Sphk1)-driven production of sphingosine-1-phosphate (S1P), thus remodeling intracellular calcium cycling in beige adipocytes. Notably, treatment with a designed peptide against IL-11Ra in obese mice effectively alleviates fat accumulation and obesity-associated disorders. Taken together, our study defines a physiological and noncanonical mechanism of beige adipocyte-derived IL-11 in energy metabolism, which may serve as a promising target for the treatment of obesity.

BACKGROUND AND AIMS: Helicobacter pylori is a persistent gastric microbe with systemic consequences beyond the stomach, yet its contribution to host lipid dysregulation remains unclear. METHODS: We analyzed clinical data from 57,295 adults with documented H. pylori status and detailed lipid profiles, including the non-HDL-C to HDL-C ratio (NHHR). Mechanistic validation was performed using in vitro and in vivo H. pylori PMSS1 infection models, combined with single-cell RNA sequencing, molecular analyses, histopathology, and lipidomics. RESULTS: Helicobacter pylori infection was associated with increased LDL cholesterol and triglycerides, reduced HDL cholesterol, and elevated NHHR, which independently predicted hyperlipidemia risk. At the mechanistic level, H. pylori infection consistently suppressed gastric expression of Gpihbp1, a key mediator of lipoprotein lipase-dependent lipid transport. Infected mice developed systemic hyperlipidemia and exhibited lipidomic remodeling characterized by glycerolipid accumulation and reduced phosphatidylcholine species. Importantly, genetic deficiency of Gpihbp1 promoted gastric H. pylori colonization and exacerbated mucosal inflammation, revealing a reciprocal interaction between host lipid metabolism and bacterial persistence. CONCLUSION: These findings define a microbiota-host lipid transport axis linking chronic H. pylori infection to dyslipidemia and suggest that integrated targeting of microbial infection and metabolic dysfunction may offer therapeutic benefit.

Obesity and its related comorbidities have become increasingly challenging in public health globally, and white adipose tissue (WAT) browning enhances energy expenditure and provides a promising therapeutic strategy for treating obesity. However, few drugs have been clinically approved for promoting WAT browning largely due to the involvement of complex signaling pathways, which limits the application of traditional drug screening approaches. Thus, a cross-species gene set that marks the adipose browning process was constructed, and a systematic strategy for compound screening was developed. By integrating single-nucleus and bulk RNA sequencing data from both humans and mice, we established a signature gene set named "white adipose tissue browning-associated gene" (WAT-BAG) through differential gene expression analysis. Candidate compounds were identified by integrating the WAT-BAG gene set with the Connectivity Map (CMap) database, followed by functional validation both in vitro and in vivo. Among the candidates, BRD-K78062244 was ranked as a top compound that induced transcriptional changes resembling the WAT-to-BAT transition. Further analysis revealed that BRD-K78062244 activated the PPAR signaling pathway and inhibited lipid droplet accumulation in adipocytes in vitro. Moreover, intra-inguinal injection of BRD-K78062244 enhanced glucose handling capacity in lean adult mice, accompanied by transcriptomic evidence of enhanced thermogenesis and suppression of lipogenic programs in adipose tissue. This study introduces a transcriptome-guided drug screening strategy that overcomes the limitations of conventional single-target approaches and highlights the potential of BRD-K78062244 in metabolic remodeling. Our findings offer a new framework for identifying compounds that promotes WAT browning via multi-omics-derived gene signatures.