Loss of Stearoyl-CoA Desaturase-1 Activity Induced Leptin Resistance in Neuronal Cells

• Published in: Biological & pharmaceutical bulletin Vol. 40; no. 8; pp. 1161 - 1164
• Main Authors: Thon, Mina, Hosoi, Toru, Chea, Chanbora, Ozawa, Koichiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2017; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Brain; Cell Line, Tumor; Desaturase; Fatty acids; High fat diet; Humans; leptin; Leptin - metabolism; leptin resistance; Neurons - drug effects; Neurons - metabolism; Obesity; palmitate; Palmitates - pharmacology; Palmitic acid; Pathogenesis; Phosphorylation; Phosphorylation - drug effects; Receptors, Leptin - genetics; RNA Interference; saturated fatty acid (SFA); Stat3 protein; STAT3 Transcription Factor - metabolism; Stearoyl-CoA desaturase; Stearoyl-CoA Desaturase - antagonists & inhibitors; Stearoyl-CoA Desaturase - metabolism; stearoyl-CoA desaturase-1 (SCD1); Transcription; saturated fatty acid (SFA); leptin resistance; palmitate; leptin; stearoyl-CoA desaturase-1 (SCD1); obesity
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b17-00311

The lack of response to leptin’s actions in the brain, “leptin resistance,” is one of the main causes of the pathogenesis of obesity. However, although high-fat diets affect sensitivity to leptin, the underlying mechanisms of leptin resistance are still an enigma. Here we examined the effect of excess saturated fatty acids (SFAs) on leptin signaling in human neuronal cells. Palmitate, the principle source of SFAs in diet, induced leptin resistance in a human neuroblastoma cell line stably transfected with the Ob-Rb leptin receptor (SH-SY5Y-ObRb). We next investigated the function of stearoyl-CoA desaturase-1 (SCD1), an enzyme which converts SFAs into monounsaturated fatty acids (MUFAs), on leptin-induced signaling. We found that reduction of SCD1 activity, through SCD1 inhibition and knockdown, impairs leptin-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in human neuronal cells. Our findings suggested that SCD1 plays a key role in the pathophysiology of leptin resistance in neuronal cells associated with obesity.