From the Guidelines
Glucocorticoids have a profound impact on lipid metabolism, leading to increased total cholesterol, VLDL, and triglycerides, as well as changes in LDL particle size and density, primarily through weight gain, insulin resistance, and altered lipoprotein production 1.
Key Effects on Lipid Metabolism
- Weight gain and insulin resistance are key factors contributing to the dyslipidemic effects of glucocorticoids.
- Increased total cholesterol, VLDL, and triglycerides are common lipid profile changes associated with glucocorticoid therapy.
- Alterations in LDL particle size and density also occur, potentially increasing the risk of atherosclerotic cardiovascular disease.
Mechanisms and Clinical Implications
The mechanisms by which glucocorticoids affect lipid metabolism involve the stimulation of lipolysis in peripheral adipose tissue and the enhancement of lipogenesis and VLDL production in the liver 1.
Management and Monitoring
Given the potential for glucocorticoids to adversely affect lipid profiles, patients on long-term glucocorticoid therapy should be closely monitored for dyslipidemia, and lifestyle modifications, including diet and exercise, are recommended to mitigate these effects 1.
Recent Guidelines and Recommendations
Recent guidelines suggest that the impact of glucocorticoids on lipid metabolism should be considered in the context of overall cardiovascular risk, and that lifestyle interventions and statin therapy may be beneficial in managing dyslipidemia in patients treated with glucocorticoids 1.
From the Research
Effects of Glucocorticoids on Lipid Metabolism
- Glucocorticoids (GCs) have been shown to increase total cholesterol and low-density lipoprotein cholesterol levels, with these levels increasing on day 3 of GC administration and remaining similar after day 7 2.
- High-density lipoprotein cholesterol levels have been found to significantly increase on day 3 of GC administration, with a gradual increase from days 3 to 28 2.
- Triglyceride levels have been reported to remain unchanged during GC treatment 2.
- GCs have been found to promote preadipocyte conversion to mature adipocytes, causing hyperplasia of the adipose tissue, and have acute antilipolytic effects on adipocytes 3.
- The effects of GCs on adipose tissue lipid metabolism are complex and can vary depending on the dose and duration of treatment, as well as the specific mechanisms involved 3, 4, 5.
Mechanisms of Glucocorticoid-Induced Changes in Lipid Metabolism
- GCs can increase the amount of fatty acids in circulation, which are then available for ectopic fat distribution, including in the liver, muscle, and central adipocytes 3, 4.
- GCs can also increase de novo lipid production in hepatocytes through increased expression of fatty acid synthase 3, 4.
- The glucocorticoid receptor (GR) plays a key role in mediating the effects of GCs on adipose tissue function and lipid metabolism, with studies in animal models demonstrating that suppressing GR signaling can improve insulin sensitivity and metabolic profiles 6.