ABSTRACT
Fibroblast growth factor 21 (FGF21) is a peptide hormone predominantly secreted by the liver and plays a crucial role in maintaining whole-body energy metabolism and regulating insulin sensitivity. A large number of clinical studies have demonstrated that serum FGF21 levels are increased in obese patients with non-alcoholic fatty liver disease (NAFLD), and high circulating FGF21 is a sensitive biomarker for predicting the onset and progression of NAFLD. Injection of exogenous FGF21 can effectively alleviate pathological process in both animal models and NAFLD patients. This review aims to describe the molecular mechanism underlying the hepatoprotective effects of FGF21; to summarize the current data and challenges of the clinical trials on FGF21 analogs and receptor agonists in the treatment of NAFLD and nonalcoholic steatohepatitis (NASH); and to speculate the future directions of FGF21 as a diagnosis and treatment for NAFLD.
ABSTRACT
AIM:To explore the effect of CXCL16 deficiency on streptozocin ( STZ)-induced diabetic nephrop-athy in mice.METHODS:CXCL16 knockout ( C16 KO) mice (8 years old) were used to build up diabetes model by treating with STZ.Age-and gender-matched wild-type ( WT) C57BL/6J mice treated with STZ were used as control.All mice were fed with chow diets for 12 weeks, and the development of diabetic nephropathy was evaluated.RESULTS:Compared with the WT mice treated with STZ, C16 KO mice treated with STZ presented lower fasting glucose levels and better glucose tolerance power.C16 KO mice treated with STZ also had lower urine protein levels and smaller areas of glo-merular injury as compared with WT mice treated with STZ.Furthermore, CXCL16 deficiency decreased the contents of re-nal reactive oxygen species ( ROS) , malondialdehyde ( MDA) and oxidized low-density lipoprotein ( ox-LDL) and the mR-NA expression of lectin-like oxidized low-density lipoprotein receptor 1 (Lox-1), and attenuated the expression of renal in-flammatory factors including tumor necrosis factor α( TNF-α) and interleukin 6 ( IL-6) , as well as chemokines including intercellular cell adhesion molecular 1 (ICAM-1) and chemokine C-X-C motif ligand 1 (CXCL1).CONCLUSION:CX-CL16 deficiency obviously inhibits the development of STZ-induced diabetic nephropathy in mice.
ABSTRACT
Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels.