Abstract
About 30% of diabetes patients suffer from varying degrees of depression. Diabetes itself is associated with abnormal carbohydrate and energy metabolism. Whether chronic stress-induced depression-like behavior impacts the metabolome of blood plasma and urine in diabetes is not clear. This study aimed to investigate the effect of chronic stress on metabolome of plasma and urine in spontaneously diabetic Goto-Kakizaki (GK) rats. The GK rats were subjected to 8 weeks' chronic unpredictable mild stress (CUMS) to induce depression-like behavior. Metabolome analysis of blood plasma and urine using liquid chromatography mass spectrometry (LC/MS) was performed. Multivariate data analysis was used to evaluate the data. Behavior and biochemical assay confirmed the successful establishment of CUMS-induced depression-like behavior model in rats. Disturbance of 20 plasma metabolites and 16 urine metabolites were altered in CUMS-induced depression GK rats as compared to control ones. These disturbed metabolites were involved in fatty acid metabolism, sphingolipid metabolism, phenylalanine metabolism, citrate cycle, glycolysis, glutathione metabolism, and nicotinate and nicotinamide metabolism. This study suggest that chronic stress-induced depression-like behavior may further disturb diabetes-itself energy metabolome. The plasma and urine lipid metabolites monitoring may be useful for early detection of depression in patients with diabetes mellitus.
Highlights
Lifelong medication, risk of various complications, and heavy care burdens result in psychosocial stress in patients with diabetes mellitus, which is detrimental to mental health and often lead to depression [1]
Biochemical test was done to show that chronic stress treatment reduces serotonin (5-HT) and dopamine (DA) levels in chronic unpredictable mild stress (CUMS) model group rats [from 62.09 to 22.17 ng/mL (p
Few researches focused on the impact of chronic stress-induced depression-like behavior on blood plasma and urine metabolome in diabetes patients or in experimental diabetic rats, metabolome analysis has been proposed for screening for depression [25, 26]
Summary
Risk of various complications, and heavy care burdens result in psychosocial stress in patients with diabetes mellitus, which is detrimental to mental health and often lead to depression [1]. About 30% of diabetes patients experience varying degree of depression [2, 3], and have worse outcomes [4, 5]. The pathological mechanisms underlying depression are complex and still not fully understood. Abnormity of catecholamine neurotransmitters in the brain have been considered the primary cause of depression, Levels of 5-hydroxytryptamine (5-HT), noradrenaline (NE), and dopamine (DA) are generally reduced in patients with depression [6]. Neuroinflammation is associated with the occurrence and development of depression [7]. Evidences suggested that depression might be related to carbohydrate and energy metabolism abnormity [8, 9]
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