ARS | Publication request: Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys

Submitted to: Prostaglandins Leukotrienes and Essential Fatty Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 8, 2010
Publication Date: March 5, 2011
Repository URL: http://www.sciencedirect.com/science/article/pii/S0952327810002103
Citation: Laugero, K.D., Smilowitz, J.T., German, J.B., Jarcho, M.R., Mendoza, S.P., Bales, K.L. 2011. Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys. Prostaglandins Leukotrienes and Essential Fatty Acids. 84(3-4):71-8.

Interpretive Summary: The causes and treatment of psychiatric and cognitive diseases remain to be poorly understood. Fatty acid dysregulation and deficiency may be linked to the development of these central nervous system (CNS) diseases. CNS diseases ranging from mood disorders to attention deficit and hyperactivity disorder have been shown to be associated with fatty acid deficiencies and with alterations in specific fatty acid metabolites. For example, depression has been associated with increased plasma ratios of arachidonate:eicosapentaenate (AA:EPA) and omega-6:omega-3 fatty acid ratios, and lower EPA and docosahexaenoic acid (DHA) in circulating lipids such as phospholipids and cholesterol esters. Exposure to chronic psychological stress, particularly of social origin, commonly precedes the onset of psychiatric disease and stress is a primary risk factor for the development of these brain diseases. However, some persons are more or less vulnerable to stress and the development of these diseases. Abnormally high or low hormonal (e.g., cortisol) responses to psychological stress have been proposed as a mechanism that leads to diseases of the brain. Previous reports also suggest that these shifts in the hormonal responses to stress may be related to fatty acid metabolism. In this study, we examined in a non-human primate model of chronic social stress whether fatty acid status in circulating lipids could be altered by chronic social stress and if changes in the plasma concentration of fatty acid metabolites would explain differences in the hormonal responses to stress. Our results are consistent with previously reported fatty acid profiles in stress-related CNS diseases. Moreover, our findings are the first to possibly expose specific fatty acid markers of chronic psychological stress and show a possible connection between fatty acid status and response of key metabolic and neurobehavioral hormones, adiponectin and cortisol.

Technical Abstract: Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol; insulin; adiponectin) responsiveness to acute stress (AS) were assessed in a primate model of chronic social stress (CS). Compared to controls (not exposed to CS), CS increased (P=0.05) circulating triacylglycerol (TG) and phosphatidylethanolamine (PE) n-6/n-3 and reduced (P=0.05) cholesterol ester (CE) 16:1n7 and phosphatidylcholine (PC) 18:1n7, suggesting lower omega-3 FA status and stearoyl-CoA desaturase activity, respectively. Cortisol responses to AS positively correlated with TG n-6/n-3 (r=0.93; P=0.007), but only in CS monkeys. The adiponectin response to AS inversely correlated with CE n-6/n3 (r=-0.89; P=0.045) and positively with TG 16:1n7 (r=0.98; P=0.004), only in CS monkeys. Our results are consistent with previously reported FA profiles in stress-related psychopathology and suggest that compositional changes of specific lipid FAs may form new functional markers of chronic psychological stress.