Non-alcoholic fatty liver disease (
NAFLD) is a common health problem with a high mortality burden due to its liver- and vascular-specific complications. It is associated with
obesity, high-fat diet as well as with
type 2 diabetes mellitus (T2DM) and
metabolic syndrome (MetS). Impaired hepatic
fatty acid (FA) turnover together with
insulin resistance are key players in
NAFLD pathogenesis.
Peroxisome proliferator-activated receptors (PPARs) are involved in
lipid and
glucose metabolic pathways. The novel concept is that the activation of the PPARα subunit may protect from
liver steatosis.
Fenofibrate, by activating PPARα, effectively improves the atherogenic
lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the
drug against
liver steatosis. Namely,
fenofibrate-related PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore,
fenofibrate reduces hepatic
insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-
alcoholic steatohepatitis pathogenesis. These include
tumor necrosis factor-α, intercellular
cell adhesion molecule-1,
vascular cell adhesion molecule-1 and
monocyte chemoattractant protein-1. Consequently,
fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that
fenofibrate can limit
liver steatosis associated with high-fat diet, T2DM and
obesity-related
insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small,
fenofibrate was used as a part of multifactorial approach, while histological data were absent. In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.