Glucocorticoid-Induced Fatty Liver Disease.
Leili RahimiAman RajpalFaramarz Ismail-BeigiPublished in: Diabetes, metabolic syndrome and obesity : targets and therapy (2020)
Glucocorticoids (GCs) are commonly used at high doses and for prolonged periods (weeks to months) in the treatment of a variety of diseases. Among the many side effects are increased insulin resistance with disturbances in glucose/insulin homeostasis and increased deposition of lipids (mostly triglycerides) in the liver. Here, we review the metabolic pathways of lipid deposition and removal from the liver that become altered by excess glucocorticoids. Pathways of lipid deposition stimulated by excess glucocorticoids include 1) increase in appetite and high caloric intake; 2) increased blood glucose levels due to GC-induced stimulation of gluconeogenesis; 3) stimulation of de novo lipogenesis that is augmented by the high glucose and insulin levels and by GC itself; and 4) increased release of free fatty acids from adipose stores and stimulation of their uptake by the liver. Pathways that decrease hepatic lipids affected by glucocorticoids include a modest stimulation of very-low-density lipoprotein synthesis and secretion into the circulation and inhibition of β-oxidation of fatty acids. Role of 11β-hydroxysteroid dehydrogenases-1 and -2 and the reversible conversion of cortisol to cortisone on intracellular levels of cortisol is examined. In addition, GC control of osteocalcin expression and the effect of this bone-derived hormone in increasing insulin sensitivity are discussed. Finally, research focused on gaining a better understanding of the dose and duration of treatment with glucocorticoids, which leads to increased triglyceride deposition in the liver, and the reversibility of the condition is highlighted.
Keyphrases
- fatty acid
- high glucose
- blood glucose
- insulin resistance
- endothelial cells
- type diabetes
- glycemic control
- low density lipoprotein
- adipose tissue
- diabetic rats
- poor prognosis
- blood pressure
- body composition
- metabolic syndrome
- high fat diet
- body mass index
- oxidative stress
- drug induced
- nitric oxide
- hydrogen peroxide
- soft tissue
- stress induced