Combination effects of a fatty diet and exercise on the depressive state and cardioprotection in apolipoprotein E knockout mice with a change in RCAN1 expression

Abstract

Objective: Regulator of calcineurin 1 (RCAN1) controls plasticity of the nervous system and depressive conditions by regulating brain-derived neurotropic factor (BDNF) and plays a crucial role in neural and cardiac pathways. The apolipoprotein E gene (ApoE) is a robust risk factor for progression of Alzheimer's disease. A fatty diet is considered detrimental for metabolic disorders, such as obesity and cardiovascular diseases.

Methods: We examined the neuronal and cardiac protective roles of RCAN1 in ApoE-/- mice that were fed a high- or low-fat diet with and without voluntary movement for 3 months. Organ weights, laboratory data, histology, RNA expression, and behavior were examined.

Results: A high-fat diet with exercise improved depressive function, as examined by the forced swimming test, and RCAN1 mRNA expression was induced in the hippocampus. A low-fat diet with exercise resulted in a reduced body weight, higher heart weight/body weight ratio, and lower circulating triglyceride levels compared with a low-fat diet without exercise. RCAN1 mRNA expression was increased in cardiomyocytes in ApoE-/- mice.

Conclusions: The combination of a high-fat diet and exercise might reduce depressive function, whereas a low-fat diet with exercise leads to cardioprotection. Induction of RCAN1 expression might affect neuroplasticity and cardiac function.

Keywords: High-fat diet; apolipoprotein E knockout; brain-derived neurotropic factor; cardioprotection; exercise; low-fat diet; regulator of calcineurin 1.

Figure 1.

RCAN1 mRNA expression in (a) the hippocampus and (b) heart in each group. *P < 0.05 vs. the HFNE group, ^†P < 0.05 vs. the LFNE group. Error bars represent the standard deviation. RCAN1, regulator of calcineurin 1; HFEX, high-fat diet with exercise; HFNE, high-fat diet with no exercise; LFEX, low-fat diet with exercise; LFNE, low-fat diet with no exercise.

Figure 2.

BDNF mRNA expression in (a) the hippocampus and (b) heart in each group. ^ΔP<0.05 vs. the HFEX group. Error bars represent the standard deviation. BDNF, brain-derived neurotrophic factor; HFEX, high-fat diet with exercise; HFNE, high-fat diet with no exercise; LFEX, low-fat diet with exercise; LFNE, low-fat diet with no exercise.

Figure 3.

Results of the open field test and the novel object recognition test. There were no significant differences in the percent time in the center in the open field test (locomotor activity) (a) and exploration time of recognizing a novel object (recognition memory) (b) among the four groups. Error bars represent the standard deviation. HFEX, high-fat diet with exercise; HFNE, high-fat diet with no exercise; LFEX, low-fat diet with exercise; LFNE, low-fat diet with no exercise.

Figure 4.

Results of the Morris water maze test. There was no significant difference in the time of escape latency among the four groups. Error bars represent the standard deviation. HFEX, high-fat diet with exercise; HFNE, high-fat diet with no exercise; LFEX, low-fat diet with exercise; LFNE, low-fat diet with no exercise.

Figure 5.

Results of the forced swimming test. *The swim distance on days 1 and 2 in the HFEX group was significantly longer than that in the HFNE group (P<0.05) (a). ^△The time to immobility on day 2 in the HFEX group was significantly shorter than that in the HFNE group (P<0.05) (b). Error bars represent the standard deviation. HFEX, high-fat diet with exercise; HFNE, high-fat diet with no exercise.