Fenofibrate Usage for Diabetes Damage

Fenofibrate, also known as FEN, is a drug that is used to lower cholesterol levels. It works by blocking the absorption of dietary cholesterol in the small intestine and therefore, reduces the amount of cholesterol that enters the bloodstream. Fenofibrate has been shown to be effective in reducing LDL (bad) cholesterol levels by up to 20% and it is approved for use in the United States and Europe. Fenofibrate is a safe and effective drug and it can be used in conjunction with other medications to help reduce LDL levels.

The mechanism of action of fenofibrate is not fully understood, but it is believed to work by inhibiting the activity of a protein called Niemann-Pick C1-Like 1 (NPC1L1). NPC1L1 is responsible for the transport of cholesterol from the intestine into the cells and fenofibrate blocks its activity.

Diabetes mellitus (DM) type 1 is characterized as an autoimmune disease whereby islet beta cells are destroyed resulting in a defect in insulin production and secretion. This abnormality in insulin synthesis causes defects in glucose metabolism which can lead to serious complications and in some cases, mortality.

DM-1 causes oxidative damage when it generates reactive oxygen species (ROS). This oxidative damage then affects spermatogenesis which in turn affects the male fertility. As well as this, ROS damages lipids, cell proteins and DNA. ROS also stimulates nitric oxide synthase (iNOS) production and p38 mitogen-activated protein kinase (MAPK) activation, resulting in testicular cell inflammation due to the release of pro-inflammatory cytokines.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isotypes, all of which are encoded by variable genes: PPAR alpha, beta/delta and gamma. PPARs are involved in a variety of functions including lipid metabolism, glucose homeostasis, cellular proliferation and differentiation. PPAR alpha stimulation causes an increase in gene expression of hemeoxygenase-1 (HO-1) and superoxide dismutase (SOD).

PPARs also have both pro-inflammatory and anti-inflammatory properties. They are highly expressed in the liver, where anti-lipid drugs such as fibrates act on these receptors to regulate lipoprotein metabolism, fatty acid oxidation and fatty acid transport within hepatic cells.

It has been shown that fenofibrate has positive effects for people who have diabetes-related damage because it binds to and activates PPAR alpha. This results in the inhibition of iNOS expression and signaling pathways such as p38 MAPK. This also means that the interaction between fenofibrate and PPAR alpha leads to a decrease in interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production.

Aziz et al., 2019 investigated the use of fenofibrate on rats with testicular damage from streptozotocin-induced type 1 diabetes. Aziz and his colleagues showed that fenofibrate treatment managed to reverse some of the diabetic testicular damage and it resulted in the normalization of the serum testosterone level. As well as this, the use of fenofibrate on these rats resulted in a decrease in pro-inflammatory cytokine levels in testicular tissue.