Abstract
Excessive intake of fat is a major risk factor for lifestyle-related diseases such as heart disease and also affects brain function such as object recognition memory, social recognition, anxiety behavior, and depression-like behavior. Although oxytocin (OXT) has been reported to improve object recognition, social recognition, anxiety behavior, and depression-like behavior in specific conditions, previous studies did not explore the impact of OXT in high-fat diet (HFD)-fed mice. Furthermore, it remains unclear whether intake of HFD affects OXT/oxytocin receptor (OXTR) in the brain. Here, we demonstrated that peripheral OXT administration improves not only social recognition but also object recognition and depressive-like behavior in HFD-fed mice. In contrast, peripheral OXT administration to HFD-fed male mice increased fear and anxiety-related behavior. In addition, we observed that intake of HFD decreased OXTR and c-fos mRNA expression in the hippocampus, specifically. Furthermore, peripheral OXT administration increased OXT mRNA expression in the hypothalamus. Altogether, these findings suggest that OXT has the potential to improve various recognition memory processes via peripheral administration but also has side effects that increase fear-related behavior in males.
Highlights
Excessive fat intake is a major risk factor for lifestyle-related diseases such as obesity, diabetes, and metabolic syndrome
The OXT mice spent more time with the novel mice than the familiar one (ND: p = 0.042; high-fat diet (HFD): p = 0.79; and HFD + OXT: p = 0.048; Figure 3E). These results indicate that the intake of a HFD impaired the ability of mice in social recognition but not their sociability, and that OXT administration ameliorated their impaired social recognition
In the object location test (Figure 3H), the ND mice spent a longer time investigating the novel location of the object than the familiar object location, whereas the HFD mice spent a similar length of time investigating the objects in the novel and familiar location
Summary
Excessive fat intake is a major risk factor for lifestyle-related diseases such as obesity, diabetes, and metabolic syndrome. Previous studies have shown that intake of a high-fat diet (HFD) decreases social recognition and object recognition memory, and increases anxiety related behavior as well as depression-like behavior [6,7,8,9]. Oxytocin (OXT) is a 9-amino acid neuropeptide hormone synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) [10] and is secreted into blood by axons projecting axons to the posterior pituitary gland [11]. Synthesized OXT has various physiological functions in a wide range of peripheral tissues, including the mammary gland, uterine smooth muscle, tongue, and bone tissue.
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