A novel solid beverage RLMCR prevents obesity-related metabolic disorders through the gut-adipose axis.

BACKGROUND

The global obesity epidemic and associated metabolic comorbidities have imposed an insurmountable strain on healthcare systems, underscoring the urgent need for simple, early interventions to curb obesity at its onset. To address this problem, we developed a novel solid beverage RLMCR (Chinese National Invention Patent No. ZL 202410541939.2) and proved its therapeutic effects on established obesity, yet its preventive potential and underlying mechanisms remain unelucidated.

PURPOSE: This study aimed to further explore the preventive role of RLMCR on diet-induced obesity and elucidate its mechanism via the gut-adipose axis.

METHODS

Male C57BL/6J mice were given RLMCR throughout high-fat diet (HFD) feeding to assess its preventive efficacy against obesity. Post-intervention, key metabolic indices, including body weight, fat percentage, and glucose tolerance, were measured. Subsequently, energy expenditure was monitored, and cold tolerance assays, adipose histomorphology, and thermogenic gene expression analysis were conducted. To characterize the modulatory effects of RLMCR on gut microbiota, 16S rDNA sequencing and untargeted metabolomics analysis were performed. Fecal microbiota transplantation (FMT) was finally conducted to verify the mediating role of gut microbiota in the beneficial effects of RLMCR.

RESULTS

RLMCR markedly mitigated HFD-induced body weight gain and glucolipid metabolic disturbances, while significantly augmenting energy expenditure and cold tolerance. Besides, RLMCR facilitated white adipose tissue browning, as reflected by the emergence of multilocular adipocytes and the upregulation of core thermogenic genes including UCP1 and PGC-1α. Moreover, RLMCR effectively restored the HFD-induced gut microbial disruption and notably enriched the abundance of Akkermansia. FMT from RLMCR-treated donor mice recapitulated the enhanced adipose browning, thereby replicating the metabolic benefits of RLMCR in recipient mice.

CONCLUSION

RLMCR effectively prevented HFD-induced obesity and metabolic dysfunction via gut microbiota-mediated adipose browning. These findings offer a novel preventive strategy for obesity and support the development of RLMCR-based anti-obesity products.