Metabolic effects of basic fibroblast growth factor in streptozotocin-induced diabetic rats: A 1H NMR-based metabolomics investigation

Abstract

The fibroblast growth factors (FGFs) family shows a great potential in the treatment of diabetes, but little attention is paid to basic FGF (bFGF). In this study, to explore the metabolic effects of bFGF on diabetes, metabolic changes in serum and feces were analyzed in the normal rats, the streptozocin (STZ)-induced diabetic rats and the bFGF-treated diabetic rats using a 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Interestingly, bFGF treatment significantly decreased glucose, lipid and low density lipoprotein/very low density lipoprotein (LDL/VLDL) levels in serum of diabetic rats. Moreover, bFGF treatment corrected diabetes-induced reductions in citrate, lactate, choline, glycine, creatine, histidine, phenylalanine, tyrosine and glutamine in serum. Fecal propionate was significantly increased after bFGF treatment. Correlation analysis shows that glucose, lipid and LDL/VLDL were significantly negatively correlated with energy metabolites (citrate, creatine and lactate) and amino acids (alanine, glycine, histidine, phenylalanine, tyrosine and glutamine). In addition, a weak but significant correlation was observed between fecal propionate and serum lipid (R = −0.35, P = 0.046). Based on metabolic correlation and pathway analysis, therefore, we suggest that the glucose and lipid lowering effects of bFGF in the STZ-induced diabetic rats may be achieved by activating microbial metabolism, increasing energy metabolism and correcting amino acid metabolism.

FGF1 — a new weapon to control type 2 diabetes mellitus

“…This finding is however in contrast to a more recent (2016) metabolomics study, in which intravenous injection of FGF2 into STZ-induced diabetic rats lowered blood glucose levels 38 . Additionally, to our knowledge, no data describing the effects of central injection of FGF2 in diabetic animals is currently available.…”

Intrarenal delivery of bFGF-loaded liposome under guiding of ultrasound-targeted microbubble destruction prevent diabetic nephropathy through inhibition of inflammation

“…bFGF can reduce structural and functional damage in chronic kidney disease [19], reduce pro-inflammatory signals in acute kidney injury [18] and has tremendous therapeutic potential for diabetes [20,21]. However, it remains difficult to apply bFGF in the clinic because of its short half-life, low stability and poor penetration of the cellular membrane.…”

“…bFGF plays an important role in the processes involved in cell growth, proliferation, differentiation, survival, and malignant transformation. Numerous studies have demonstrated that bFGF is a pleiotropic cytokine, and exogenous bFGF can promote renal repair in acute kidney injury [18] and reduces pro-inflammatory signals [19], and in chronic kidney disease, it can reduce structural and functional damage [20], and it also has anti-apoptotic activity. However, the concrete mechanism by which bFGF acts remains unclear.…”

“…However, the concrete mechanism by which bFGF acts remains unclear. Moreover, bFGF can reduce blood glucose, blood lipid levels and other levels in diabetic rats [20] and can intervene the diabetic cardiomyopathy [21,22]. Therefore, bFGF has great potential for the treatment of diabetic nephropathy.…”

Functional characterisation of gut microbiota and metabolism in Type 2 diabetes indicates thatClostridialesandEnterococcuscould play a key role in the disease

“…and animal studies, showing an inverse relationship with body weight and25 adiposity(Lin et al, 2016, Chambers et al, 2018. Interestingly, higher levels of acetate26 in distal colon, which contributes to the regulation of central appetite(Frost et al, 27 2014), are considered more effective than in proximal colon.…”