<p>Glucocorticoid-Induced Fatty Liver Disease</p>

Abstract

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 verylow-density lipoprotein synthesis and secretion into the circulation and inhibition of βoxidation 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.

Effects of steroid growth promoter on morphological and biochemical adaptations in liver of broiler

“…Similar results were reported by other groups [ 28 - 31 ] stating that the chronic elevations in GCs may be associated with increased incorporation of liver fat. GCs stimulate hepatic gluconeogenesis and increase the hepatic synthesis and storage of glycogen in the liver [ 30 ]. In response to elevated blood glucose, there may be a compensatory increase in insulin secretion.…”

“…Further, a wide cytoplasmic vacuolization resulting from intracellular edema and lipid accumulation was also observed. DEX inhibits the synthesis of arachidonic acid and prostaglandin which normally act as antiaggregant agents [ 30 ]. This, together with the likely occurrence of hypertension and polycythemia in the liver may have caused the sinusoidal dilatation and congestion, which have been noticed in the DEX-treated group of the present study.…”

Selective Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Attenuates High-Fat Diet-Induced Hepatic Steatosis in Mice

“… 12 11β-HSD1 was initially identified, purified, and found to be abundantly expressed in the liver where it mainly functions as a reductase that converts inactive 11-dehydrocorticosterone to corticosterone in rodents (cortisone to cortisol in human). 13 11β-HSD1 is also expressed in white adipose tissue, and functions as an amplifier of glucocorticoids (corticosterone in rodents and cortisol in humans). Hepatic transgenic overexpression of 11β-HSD1 in mice induced fatty liver and insulin resistance without obesity.…”

Macrophage migration inhibitory factor deficiency aggravates effects of fructose‐enriched diet on lipid metabolism in the mouse liver

“…The expression of genes involved in lipogenesis, Fas, Scd1 and Lpl, were examined by qPCR (Figure 1C). The effect of fructose diet was detected for Fas [F (1,20)…”

“…18 GCs exert their effects through the glucocorticoid receptor (GR) 19 and may affect lipid deposition by inhibiting fatty acid β-oxidation, increasing FFA uptake by the liver, and stimulating the expression of genes involved in hepatic DNL, particularly ACC and FAS. 20 Liver, together with the adipose tissue, plays a central role in the regulation of energy homeostasis. Generally, prolonged metabolic stress induced by chronic nutrient excess leads to visceral adipose tissue dysfunction which results in increased hepatic lipid influx and consequent ectopic lipid accumulation.…”