Abstract
Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism. We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters. ApoE−/− mice were fed an atherogenic diet for 14 weeks and were randomly assigned to control (saline) or FGF21 (0.1 mg/kg) treatment group (n = 10/group) for 5 weeks. Plaque size in the aortic arch/valve areas and cardiovascular risk markers were evaluated in blood and tissues. The effects of FGF21 on various atherogenesis-related pathways were also assessed. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the FGF21 group than in controls after treatment. FGF21 significantly decreased body weight and glucose concentrations, and increased circulating adiponectin levels. FGF21 treatment alleviated insulin resistance and decreased circulating concentrations of triglycerides, which were significantly correlated with plaque size. FGF21 treatment reduced lipid droplets in the liver and decreased fat cell size and inflammatory cell infiltration in the abdominal visceral fat compared with the control group. The monocyte chemoattractant protein-1 levels were decreased and β-hydroxybutyrate levels were increased by FGF21 treatment. Uncoupling protein 1 expression in subcutaneous fat was greater and fat cell size in brown fat was smaller in the FGF21 group compared with controls. Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy.
Highlights
Diabetes mellitus (DM) is a noncommunicable disorder that threatens human health because of its various complications
Weight changes were compared between the control and fibroblast growth factor 21 (FGF21) groups for the 5 weeks of treatment
The mean weight of mice in the FGF21 group began to fall from the beginning compared with that in the control group, and the difference was maintained thereafter (Figure 1A)
Summary
Diabetes mellitus (DM) is a noncommunicable disorder that threatens human health because of its various complications. As of 2019, an estimated 463 million people worldwide suffered from DM. There are many antidiabetic medications available at present and some have proven beneficial effects on the cardiovascular system as well as giving glycemic control. They have several side effects, such as genital infection with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and gastrointestinal discomfort with glucagon like peptide-1 (GLP-1) analogues. Among several candidates used for this purpose, fibroblast growth factor 21 (FGF21) has drawn much attention. This is a hormone produced mainly by the liver [2]. Administration of FGF21 for pharmacological purposes shows favorable multifaceted effects on metabolically important organs [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
