Metabolic regulation of leptin production in adipocytes: A role of fatty acid synthesis intermediates

In addition to a signal arising from the physical “stretching” of the adipocytes, metabolic and endocrine regulation of leptin production seems to operate in adipocytes. There is however a paucity of literature examining direct role of fatty acid synthesis in regulating adipocytes leptin production. To clarify the relation between fatty acid synthesis and leptin release in adipocytes, we examined leptin release from primary cultured rat epididymal adipocytes with several substances relevance to de novo fatty acid syntyhesis. Bezafibrate (0.5 or 1.0 mM), known to inhibit acetyl-CoA carboxylase, decreased leptin release to 60.3 ± 7.2 or 47.3 ± 11.9%, while cerulenin (15, 30, or 75 mM), an inhibitor of fatty acid synthase, increased it by 20.5 ± 7.7, 58.5 ± 12.1 or 105.0 ± 35.0% of the control. Exogenous pyruvate (2.5, 5.0, or 10.0 mM) and malonyl-CoA (10, 20, or 40 mM), substrates and intermediate of fatty acid synthesis, increased leptin release by 11.0 ± 3.3, 21.5 ± 5.4, or 61.0 ± 10.7%, and 11.1 ± 3.0, 41.1 ± 9.7 or 56.7 ± 7.9% of the control, respectively. Considering difference in the site of action of bezafibrate and cerulenin along fatty acid synthesis pathway, one plausible explanation is that malonyl-CoA levels act as a signal of fuel availability to trigger leptin synthesis and/or secretion in adipocytes. Keywords: Leptin secretion; Fatty acid synthesis; Malonyl-CoA; Rat adipocytes