The primary determinant of health is dietary components (17). A lot of researches showed that high-fat diets may induce obesity and affect brain function (18, 19). Our results indicated that all high-fat groups significantly increased body weights in mice, compared with the CON group at the end of this study. The n-3 PUFA group had the smallest increase, and the n-6 PUFA group had the largest increase. Moreover, the body fat mass, such as perirenal fat, peri-testicular fat, and omental fat showed the same trend as the body weight. Bruce-Keller et al. demonstrated that long-term consumption of high SFA diet induced obesity in mice (19). Increased n-3 PUFA intake may prevent obesity and reduce the body fat mass of obese subjects (20–22). Massiera et al. indicated that a high ratio of n-6/n-3 PUFA may be a risk factor for obesity in rodents and possibly in humans (23). Related studies showed that the consumption of TFA was related to changes in blood lipids (24) and obesity in animals and humans (25). All these studies were similar to our outcomes. The effect of MUFA on obesity is controversial in recent researches. Some studies indicated that MUFA could reduce blood lipids in obese rats, even prevent obesity (26). However, other studies showed that high MUFA diet improved body mass in mice (27), which was similar with our study.
High-fat diet-induced obesity leads to lipid disorders. Our results showed that the contents of C12:0, C14:0, C16:0, C22:0, total SFA, C16:1, C18:1 n-9c, total MUFA, and n-6/n-3 PUFA in the MCSFA group were markedly higher than those in other test groups. The contents of C22:6 n-3 and total n-3 PUFA were markedly lower than those in other test groups. Related researches in our research group found that compared with healthy people, lipid disorders in the brain and blood of people with cognitive dysfunction showed high levels of SFA (especially C20:0) (28), MUFA, and n-6 PUFA (29). In contract, lower level of n-3 PUFA (especially C22:6 n-3) was observed in those people (30), which was similar with our findings. The previous research of our group showed that the increased plasma SFA and MUFA was positively correlated with the incidence of mild cognitive impairment (28). Reversely, in our study, the contents of C16:0, total SFA, C18:1 n-9c, total MUFA, C20:3 n-6, C20:4 n-6, total n-6 PUFA, and n-6/n-3 PUFA in the n-3 PUFA group were markedly lower than those in most test groups. Song et al. found that with the increased ratio of serum n-3/n-6 PUFAs, the risk of cognitive impairment in the elderly decreased (31). Compared with that in the n-3 PUFA group, the LCSFA, n-6 PUFA, MUFA, and TFA groups showed lower ratio of plasma n-3/n-6 PUFAs.
The tight junction complex between endothelial cells involves transmembrane proteins (e.g. claudin-5, occludin) and scaffolding proteins (e.g. ZO-1, ZO-2), which are important for paracellular space occlusion and physical support (32). However, high-fat diets affect the expression of these proteins to undermine the permeability and integrity of intestinal barrier. Cani et al. demonstrated that the high-fat diet evidently increased intestinal permeability by reducing the expressions of occludin and ZO-1 (33). Gil-Cardoso et al. also found that the expressions of claudin-1 and ZO-1decreased in obese Wistar rats, compared with the controls (34). Moreover, AD related study found decreased expressions of claudin-1 and claudin-5 and increased blood-brain barrier (BBB) permeability in their 3D human neural cell culture microfluidic model (35). However, Yuan and Willemsen et al. indicated that n-3 PUFA supported epithelial barrier integrity and reduced IL-4 mediated permeability (36, 37). In our results, high LCSFA, MCSFA, n-3 PUFA, MUFA, and TFA diets all decreased the expression of intestinal tight junction proteins, but high n-3 PUFA diet had minimal damage to the epithelial barrier, which were consistent with previous related researches.
Furthermore, our study found that the protein expressions of BDNF in brain had different degrees of reduction in the test groups. BDNF is able to suppress appetite signals in the brain and prevent obesity (38). In addition, BDNF supports synaptic plasticity and neuronal excitability, and was important for learning and memory function (39, 40). Wu et al. indicated that SD rats fed long-term high-fat diet had decreased levels of BDNF in brain (12), which was similar to our outcome. Molteni et al. also showed that a high-fat, refined sugar diet reduced hippocampal BDNF, neuronal plasticity, and learning ability (41). In our results, the levels of 5-HT in brain decreased in the MCSFA, n-6 PUFA, MUFA, and TFA groups. Tillisch et al. demonstrated that 5-HT could enter central nervous system through gut-brain axis, which affected brain function(42).
Leptin can reduce appetite and energy intake, and regulate central nervous system inflammation as an immunomodulatory factor (43). Related researches indicated that high SFA diet was positively correlated with increased serum leptin in animals and humans (44), which was associated with the occurrence of AD (15). Several studies found that leptin resistance is associated with cognitive deficits (45, 46). However, our outcome of leptin in hippocampus was contrary to previous related researches, which might because high-fat diets decreased the rate of ghrelin transported across the BBB (47). In our study, the insulin of hippocampus in the MCSFA group increased among all groups, and decreased in the LCSFA, n-3 PUFA, and MUFA groups, compared to the CON group. Perry et al. showed that high-fat diet led to obesity and insulin resistance in rats (48). Some evidences indicated that insulin, like leptin, might have a key role in cognitive function through regulation of synaptic plasticity and trafficking of neurotransmitter receptors (49, 50). The immunoexpression of ghrelin in ileum and colon presented different degrees of reduction in six test groups of our study. Zachary et al. demonstrated that high-fat diet resulted in the permeability of BBB increasing and the active transport of ghrelin across the BBB decreasing (51).