Oral retinoids and plasma lipids

Abstract

Retinoids and rexinoids are prescribed for conditions ranging from acne vulgaris to hyperkeratosis to cutaneous T cell lymphoma. Dyslipidemia is a frequent consequence of the use of these drugs, with more than one-third of patients manifesting aberrations in triglyceride (TG) levels. The efficacy of retinoic acid derivatives is linked to their influence on lipid metabolism in the skin, which can impair systemic lipid trafficking and metabolism in some patients. Thus, baseline screening for preexisting dyslipidemia and regular follow-up lipid panels are mandated, especially when powerful agents such as bexarotene are used. Dietary modification, increased physical activity, and weight management are the cornerstones of initial management for mild hypertriglyceridemia, which is a contributor to cardiovascular risk. More severe impairments (fasting TG > 500 mg/dL) warrant pharmacologic interventions early on to reduce the risk of pancreatitis. Retinoic acid derivative action, lipid metabolism, and treatment of incident dyslipidemias are reviewed to empower prescribers in management of adverse lipid effects.

All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver

“…These findings led to the identification of a novel effect of atRA signaling in the liver. The indication of the proteomic study that atRA alters lipid and fatty acid metabolism was intriguing, because use of retinoids and RA isomers isotretinoin (13-cisRA) and alitretinoin (9-cisRA) in dermatology and in cancer treatment is associated with changes in lipid and lipoprotein metabolism, including hypertriglyceridemia, hypercholesterolemia, increased total cholesterol, and decreased high-density lipoprotein-cholesterol in about one-third of the treated patients (Lawrence et al, 2001;Staels, 2001;Brelsford and Beute, 2008;Lilley et al, 2013). The induction of SREBP1 mRNA observed in this study after treatment with 10 mM atRA is in agreement with the clinical findings, as the 10 mM atRA treatment closely mimics the RA exposures observed after retinoid therapy.…”

“…The activation of multiple pathways by atRA likely leads to diverse effects on liver physiology, including altered lipid homeostasis. In humans both excessive intake of vitamin A or retinoids and vitamin A deficiency lead to hypertriglyceridemia, elevated total cholesterol, and decreased high-density lipoprotein cholesterol (Bershad et al, 1985;Lawrence et al, 2001;Staels, 2001;Brelsford and Beute, 2008;Lilley et al, 2013). However, likely because of a dichotomy of the effects of vitamin A on the liver, the endogenous role of atRA in regulating lipid and fatty acid homeostasis and role of atRA in liver disease is not well understood.…”

The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma

“…It also decreases lipoprotein lipase activity, which hydrolyzes triglycerides into fatty acids. 65 Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are part of the superfamily of receptors that also includes retinoid receptors and others. These receptors are strongly expressed in the skin and sebaceous glands and are involved in oxidative pathways for fatty acids.…”

“…These receptors are strongly expressed in the skin and sebaceous glands and are involved in oxidative pathways for fatty acids. 65 Retinoic X receptors form heterodimers with PPARs and transactivation by rexinoids are believed to influence lipid metabolism. 1 Triglyceride elevation also is regulated by transactivation of LXR (Liver X receptor)/RXR heterodimers by sterol regulatory element-binding proteins, which are transcription regulators involved in cholesterol biosynthesis.…”

ATP-binding cassette transporter A1: From metabolism to neurodegeneration

“…One confounding factor for the use of LXR and RXR agonists in patients is the increase of triglycerides in plasma (Lilley et al, 2013; Tontonoz and Mangelsdorf, 2003). Interestingly, the only published clinical trial with LXR agonist reported adverse effects on CNS and not an increase of serum triglycerides (Katz et al, 2009).…”