Serum Free Fatty Acids Desaturase Activity Indices in Sera of Patients on Long-term High-dose Corticosteroid Treatment

Serum Free Fatty Acids Desaturase Activity Indices in Sera of Patients with Pemphigus and Bullous Pemphigoid on Long-term High-dose Corticosteroid Treatment

1.1 BACKGOUND & STUDY RATIONALE Chronic exposure to glucocorticoids exerts profound effects on subcutaneous and visceral adipose tissues, and may induce both lipolysis and lipogenesis [1].

In acute conditions (such as stress) glucocorticoids increase whole body lipolysis, and free fatty acid production and turnover. However, in chronic glucocorticoid excess conditions (such as Cushing's syndrome), this acute induction of systemic lipolysis is not sustained, and actually decreases. Moreover, glucocorticoids may act synergistically with insulin to upregulate lipogenesis, and increase triglycerides storage, mainly in the liver and visceral adipose tissue [2, 3]

Increased subcutaneous fat mass is a hallmark of Cushing's syndrome and could potentially be mediated through the activation of lipogenesis. We have recently published a study that found an upregulation of free fatty acids synthesis and desaturases genes and triglyceride synthesis genes in subcutaneous adipose tissue from subjects with Cushing's disease, further supporting the hypothesis that lipogenesis is activated in these tissues via the transcriptional activation of fatty acid synthesis and triglyceride synthesis [4]. In parallel, we saw higher levels of lipolysis in adipose tissue explants from Cushing's disease patients [4].

In general, serum free fatty acids composition is influenced by dietary fat intake, desaturating enzymes activity (in subcutaneous and visceral adipose tissues, and liver), insulin resistance and lifestyle factors such as physical activity, and obesity [5, 6, 7]. However, fasting serum free fatty acids are not directly derived from nutritional intake, but primarily originate from adipose tissue storages [8, 9] Desaturase indices, estimated as product-to-precursor fatty acid ratios, are employed in epidemiological studies. Desaturase activity indices were estimated according to the following: Stearoyl-CoA desaturase-16 (SCD-16) = 16:1(n-7) / 16:0, Stearoyl-CoA-desaturase-18 (SCD-18) = 18:1(n-9) / 18:0, Delta-5-desaturase (D6D) = 20:3(n-6) / 18:2 (n-6), and Delta-5-desaturase (D5D) = 20:4(n-6) / 20:3 (n-6).