In the present study, CUMS, a valid model of depression for rodents, was established. The pathophysiology of depression might be related to the alterations in the lipid profiles. Animal study showed that CUMS increased plasma HDL-c significantly [
25], which is different from clinical studies. Though the causes may be complicated, the discrepancy is greatly due to species specific effects. Additionally, HDLs are a class of heterogeneous lipoproteins. Different HDL subpopulations have distinct and characteristic functions, which means HDL subpopulation levels are better predictors than HDL-c levels [
26]. Further studies concerning on the subpopulation levels of HDLs are needed. It has been reported that treatment with antidepressants significantly decreased both serum TCH and HDL-c levels in patients with major depression or affective disorders [
6]. Elevated FFA had an adverse effect on body, causing damage to the pancreatic beta cell function, promoting cell apoptosis, and resulting in impaired glucose-stimulated insulin secretion [
27]. Fish oil supplementation, an auxiliary treatment for depression, was reported to reduce the serum levels of TCH and regulate HDL-c composition and metabolism [
28,
29]. In parallel with previous evidence, CUMS increased the serum levels of TCH, HDL-c and FFA, which reflected the dyslipidemia in CUMS rats. Interestingly, fish oil supplementation reversed these changes and improved the dysfunctional of lipids metabolism. On the contrary, sertraline administration failed to reverse the serum levels of TCH and HDL-c and further elevated serum concentration of FFA. It’s worth mentioning that diabetes mellitus is now perceived as an important comorbid condition in patients with depression [
30]. Stress-induced increase in FFA level may partly explain the comorbid depression and diabetes. There is considerable evidence suggests that TG play a role in adverse health conditions like metabolic syndrome (MetS) [
31]. Fish oil was found to reduce the serum level of TG level both in human and mice [
29,
32]. Similar to the previous study, fish oil or sertraline administration in CUMS groups decreased the serum level of TG. We have observed that excessive fish oil intake may significantly lower the serum lipids, and prevent the disturbance of lipid metabolism, but the effect of sertraline on lipid regulation is mild and even deteriorated. Fish oil might be an excellent replacement therapy in depression for its beneficial effects on the progression of both depression and dyslipidemia.
Adipokines, like leptin and adiponectin, are well known for their roles in energy homeostasis [
12]. Recently, accumulated studies have demonstrated the negative relationships between leptin level and severity of symptoms of depression in human [
33]. Animal studies also showed that various chronic stress [
15,
33‐
35] significantly decreased the serum concentration of leptin. Although leptin insufficiency might be associated with depression-like behavior, and leptin had antidepressant-like efficacy in rats exposed to chronic stress [
15], most clinical data indicated that antidepressant medications, such as fluxetine, imipramine, paroxetine and venlafaxine had no effect on leptin level [
16]. In the present study, the serum level of leptin was significantly down-regulated in rats exposed to CUMS. Similar to the previous studies using various antidepressants, fish oil or sertraline supplementation also failed to reverse leptin level. Chronic social-defeat stress was reported to reduce the plasma level of adiponectin, and administration of exogenous adiponectin produced antidepressant-like behavioral effects in mice [
14]. Some reports showed higher serum concentration of adiponectin in MDD subjects compared to healthy controls [
36], while other investigators found either lower levels [
11,
37] or unaltered [
38,
39] peripheral adiponectin levels in MDD individuals versus controls. In the present study, both chronic stress and antidepressants supplementary had no effect on serum concentration of adiponectin in rats. Ghrelin, a gut hormone, had an orexigenic effect on appetite and energy balance. Recent study suggested that serum level of ghrelin was decreased in patients with depression [
16]. A subgroup of healthy volunteers who received a single intravenous injection of ghrelin after an overnight fast developed elevated mood [
17]. Activation of ghrelin signaling was also reported to produce antidepressant-like response in mice [
40]. In the present study, we found a significant decrease of ghrelin level in CUMS rats, whereas this reduction was restored by supplementation of fish oil or sertraline. These findings indicated that decreased leptin and ghrelin levels might show an important role in the chronic stress-induced depression. Fish oil treatment might play an antidepressant effect through increasing the serum concentration of ghrelin, the similar mechanism to sertraline, providing a potential target for treatment of depression.