Indian lychee honey ameliorates hepatic glucose uptake by regulating the ChREBP/Glut4 axis under insulin-resistant conditions†

Many traditional treatments include honey owing to its magnificent health beneficiary effects. Recent studies have demonstrated the potent anti-diabetic activity of honey. However, its actual mechanism of action remains elusive. Moreover, being rich in sugar (75%–80%), its role in maintaining glucose homeostasis remains questionable. Although the polyphenol content of honey aids its hypoglycaemic activity, the small quantity of bioactive compounds in honey (0.5%–1.0%) may not be solely responsible for this. In the current study, an attempt was made to understand the role of Indian lychee honey (LyH) in regulating blood glucose levels under diabetic conditions. This study investigated whether LyH, although rich in sugars, can be used as an alternative to regulate glucose and lipid homeostasis under insulin-resistant conditions by regulating the ChREBP/Glut4 signalling pathway. This study was first performed in vitro in palmitic acid-induced insulin-resistant HepG2 cells. Various assays, such as FACS, GCMS, qRT-PCR, immunoblot and ChIP-qPCR, were performed to establish the anti-hyperglycaemic role of LyH in vitro. The in vitro results were subsequently confirmed in vivo using a high-fat diet-induced diabetic C57BL/6 mice model. The in vivo study was supported by several experiments, such as examining blood parameters, histopathology, double-immunohistochemistry and ELISA. Finally, the finding was validated by comparing it with a couple of GEO datasets from the NCBI database. This study found that LyH is an excellent choice for regulating blood sugar levels under diabetic conditions without significant harmful side effects. Moreover, LyH showed excellent hepatic glucose uptake activity in an insulin-independent manner. This activity is mainly governed by sugars as its main ingredient. LyH treatment also regulates hepatic lipid homeostasis by maintaining a balance between saturated and unsaturated fatty acids in insulin-resistant HepG2 cells. Further, sugar, when supplemented individually, caused severe inflammation, which was validated through histopathology, ELISA and IHC. Collectively, the findings of this study indicate that Indian LyH provides a better food matrix (the right proportion of sugars and different bioactive compounds), which significantly improves hyperglycemia and inflammation under diabetic conditions by regulating the hepatic ChREBP/Glut4 axis.