Imbalance in fatty acid (FA) metabolism is a critical factor in the development of type 2 diabetes (T2D). This study examined fatty acid composition and desaturase activities in the liver and spinal cord of male Zucker diabetic fatty (ZDF) rats, a genetic model of T2D. Heterozygous lean ZDF fa/+ animals served as controls, while homozygous obese ZDF fa/fa animals represented the diabetic group. FA profiles were determined by gas chromatography, and the activities of Δ5-desaturase (FADS1), Δ6-desaturase (FADS2), Δ9-desaturase (SCD1), and elongase of very long-chain fatty acids (ELOVL) were estimated. T2D rats displayed significantly elevated levels of monounsaturated fatty acids (MUFAs) and increased SCD1 activity in both the liver and spinal cord. In contrast, polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (AA, C20:4 n-6), were reduced. Since AA plays a fundamental role in neuronal membrane structure and signaling pathways, these alterations have particular relevance to nervous system function. Tissue-specific alterations further suggested impaired FADS1 activity in the liver and reduced elongase/FADS2 activity in the spinal cord. These findings suggest that desaturase imbalance and FA remodeling in the spinal cord might represent characteristic features of T2D and that altered FA metabolism within the nervous system may potentially serve as an early indicator of neuropathy or a predictor of increased susceptibility to diabetes-related complications.

Background/Objectives: Altered lipid metabolism is a key feature of type 2 diabetes mellitus (T2DM), yet its impact on early spinal cord involvement remains poorly understood. Distinguishing between pathological lipid accumulation and adaptive metabolic responses is essential for interpreting initial stages of neural alteration in T2DM. This study aimed to characterize spinal cord lipid composition and ATPase activities in a rat model of T2DM. Methods: Zucker diabetic fatty (ZDF) rats were used as a model of T2DM and divided into diabetic and obese groups, with lean Zucker rats as controls. ATPase activities in spinal cord tissue were measured spectrophotometrically, and lipid profiling was performed using gas chromatography with flame-ionization detection. Indices of stearoyl-CoA desaturase-1 (SCD1) and delta-5 desaturase activity (D5D) were calculated from specific fatty acid ratios as estimates of enzyme-related activity. Results: Diabetic rats exhibited significantly higher levels of free monounsaturated fatty acids (MUFAs) compared with controls, while the obese group showed a moderate increase. Elevated SCD1 indices were indicative of increased estimated MUFA synthesis. Levels of free polyunsaturated fatty acids (PUFAs), including those crucial for myelin stability, as well as ATPase activities, remained unchanged, suggesting preserved basal membrane-associated enzyme function. Conclusions: This study identifies lipid alterations in the spinal cord preceding overt neurodegenerative changes in T2DM, characterized by increased free MUFA abundance, without evidence of altered ATPase activities. These findings support the interpretation that lipid changes observed at this stage are more consistent with adaptive metabolic remodeling than with overt structural or functional neural impairment.