Momordica charantia (bitter melon) modulates adipose tissue inflammasome gene expression and adipose-gut inflammatory cross talk in high-fat diet (HFD)-fed mice

Abstract Systemic and tissue-specific inflammation has a profound influence on regulation of metabolism, and therefore, strategies to reduce inflammation are of special interest in prevention and treatment of obesity and type 2 diabetes (T2D). Antiobesity and antidiabetic properties of Momordica charantia (bitter melon, BM) have been linked to its protective effects on inflammation and gut microbial dysbiosis. We investigated the mechanisms by which freeze-dried BM juice reduces adipose inflammation in mice fed a 60% high-fat diet (HFD) for 16 weeks. Although earlier studies indicated that BM inhibited recruitment of macrophages (Mφ) infiltration in adipose tissue of rodents and reduced NF-kB and IL-1β secretions, the mechanisms remain unknown. We demonstrate that freeze-dried BM juice inhibits recruitment of Mφ into adipose tissue and its polarization to inflammatory phenotype possibly due to reduction of sphingokinase 1 (SPK1) mRNA in HFD-fed mice. Furthermore, reduction of IL-1β secretion by freeze-dried BM juice in the adipose tissue of HFD-fed mice is correlated to alleviation of NLRP3 inflammasome components and their downstream signaling targets. We confirm previous observations that BM inhibited inflammation of colon and gut microbial dysbiosis in HFD-fed mice, which in part may be associated with the observed anti-inflammatory effects in adipose tissue if HFD-fed mice. Overall, functional foods such as BM may offer potential dietary interventions that may impact sterile inflammatory diseases such as obesity and T2D.