Differences in the Effects of Saturated and Trans Fatty Acids on Metabolism and Anxiety‐Like Behavior in Mice

High-fat diets (HFDs) are linked to obesity, metabolic disorders, and increased anxiety and depression risks. However, the differential effects of saturated fatty acids (SFA) and trans-fatty acids (TFA) on neuronal-type nitric oxide synthase (nNOS) regulation of anxiety, metabolism, and mood remain unclear. This study aimed to compare the long-term impacts of SFA and TFA on obesity, metabolism, and anxiety-like behaviors, and to evaluate the role of nNOS in these processes. Mice were fed SFA and TFA diets for 12 weeks to induce obesity. Metabolic parameters such as body weight, blood glucose, blood lipids, liver enzymes, and body fat percentage were assessed. Anxiety-like behaviors were evaluated using the Open Field and Sucrose Preference Tests in Weeks 11 and 12. The effect of 7-NI (an nNOS inhibitor) on anxiety was also tested. Both diets induced obesity, glucose and lipid metabolism disorders, impaired liver function, and anxiety-like behaviors. SFA resulted in greater weight gain, while TFA caused more severe blood glucose dysregulation and hepatic dysfunction. No significant difference in nNOS protein expression was observed between the groups. However, 7-NI improved anxiety-like behaviors in SFA-fed but not TFA-fed mice. SFA primarily caused greater physical obesity, whereas TFA led to more pronounced metabolic damage. The nNOS inhibitor 7-NI reduced anxiety-like behaviors in SFA-induced obese mice but was ineffective in TFA-induced obesity, highlighting distinct metabolic and behavioral effects between these two types of fatty acids.