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. 2022 Oct 14;14(20):4302.
doi: 10.3390/nu14204302.

Neuronal Nitric Oxide Synthase Regulates Depression-like Behaviors in Shortening-Induced Obese Mice

Ping Wang  1 , Fan-Zhi Kong  1 , Xiao-Hong Hong  1 , Li Zhang  1 , Wan-Hong Zhao  1 , Jin-Cui Yang  1 , Heng Zhang  2
Affiliations

Neuronal Nitric Oxide Synthase Regulates Depression-like Behaviors in Shortening-Induced Obese Mice

Ping Wang et al. Nutrients. .

Abstract

Shortening is mainly derived from the partial hydrogenation of palm oil and widely used in fast food. Food processed with shortening contains high levels of industrial trans fatty acids. Studies have shown that there is a correlation between industrial trans fatty acids, obesity, and depression. However, the regulatory effect of neuronal nitric oxide synthase (nNOS) on depression in obese patients is still unknown. The purpose of this study was to explore mood changes in obese mice fed a high shortening diet, and to determine the regulatory effect of nNOS on depressive-like behaviors in obese mice. We used a high shortening diet-induced obesity mouse model to systematically assess the metabolic response, behavioral changes, prefrontal and hippocampal nNOS protein levels, and the effect of nNOS inhibitors (7-nitroindole) on depression-like behavior in obese mice. Interestingly, obese mice on a 9-week high-shortening diet developed short-term spatial working memory impairment and anxiety-like behavior, and obesity may be a risk factor for cognitive impairment and mood disorders. In animals fed a high shortening diet for 12 weeks, obese mice developed depression-like behavior and had significantly elevated levels of nNOS protein expression in the hippocampus and prefrontal lobe. Administration of the nNOS inhibitor 7-nitroindole could improve depression-like behaviors in obese mice, further suggesting that inhibition of nNOS is helpful for depression associated with obesity.

Keywords: 7-nitroindole; depression; neuronal nitric oxide synthase; obesity; shortening.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Experimental flow chart.
Figure 2
Figure 2
HSD exposure leads to bodyweight gain, glucose tolerance impairment, and hyperglycemia. (a) Bodyweight from 0–12 weeks of mice fed CD or HSD. (b) Fasting blood glucose of CD or HSD mice fed for 1–12 weeks. (c–e) Oral Glucose Tolerance Test (OGTT) of CD or HSD fed mice at weeks 4, 8, and 12. * p < 0.05, ** p < 0.01, *** p < 0.001. When compared with CD group, results are presented as the mean ± SD.
Figure 3
Figure 3
HSD mice have disordered lipid metabolism. ** p < 0.01, *** p < 0.001. When compared with CD group results are presented as the mean ± SD.
Figure 4
Figure 4
HSD-induced body weight was associated with morning fasting blood glucose (a) or total cholesterol (b).
Figure 5
Figure 5
Diet-induced obesity (DIO) mice show impaired short-term spatial working memory, anxiety-like, and anhedonic behaviors. Arm entries (a) and alteration (b) in elevated plus maze (YMZ), locomotor activity (c) in open field test (OFT), center distance traveled (d) and time (e) in OFT, number of entries (f) and time spent (g) in open arms of elevated plus maze (EMP), sucrose preference percentage (SPT) (h). * p < 0.05, ** p < 0.01, *** p < 0.001. When compared with the CD group, results were presented as the mean ± SD or median (quartile spacing).
Figure 6
Figure 6
The body weight of DIO mice was negatively correlated with the right arm entries (a) or distance traveled in the central zone (b) or sucrose preference percentage (c).
Figure 7
Figure 7
The expression of nNOS in the prefrontal cortex and hippocampus of DIO mice increases significantly. * p < 0.05. When compared with the CD group, the results were presented as the mean ± SD.
Figure 8
Figure 8
7-NI improves depressive behavior in DIO mice. Exercise ability (a), central travel distance (b) and time spent (c) by DIO mice in during OFT. The immobility time of mice in each group during forced swimming (d). * p < 0.05, When compared with the corresponding group, results are presented as the mean ± SD or median (quartile spacing).
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Grants and funding

H.Z. was supported by the Science and Technology Special Fund Project of Guangdong (Fund Number: 2019ST031), and the Medical Scientific Research Foundation of Guangdong, China (Fund Number: B2017020).