Elsevier

Brain Research Bulletin

Volume 164, November 2020, Pages 45-54
Brain Research Bulletin

Diet containing stearic acid increases food reward-related behaviors in mice compared with oleic acid

https://doi.org/10.1016/j.brainresbull.2020.08.012Get rights and content

Highlights

  • Diet containing stearic acid increases food reward-related behaviors compared with oleic acid diet.

  • Diet containing stearic acid influences the mesolimbic dopamine system compared with oleic acid diet.

  • Diet containing stearic acid decreased leptin levels in the serum compared with oleic acid diet.

  • Diet containing stearic acid decreased leptin signaling in the VTA compared with oleic acid diet.

Abstract

Obesity is currently a worldwide phenomenon. The consumption of calorie-rich foods is responsible for most obesity cases, but not all humans exposed to high-calorie diets develop obesity. According to recent studies, exposure to fat-rich diets may be the actual cause of obesity. Dietary long-chain fatty acids affect brain function and are linked to food intake and motivation-related behaviors. Recently, many studies have shown that different types of fatty acids play different roles in animals. In our study, the effects of stearic acid (a saturated fatty acid) and oleic acid (a monounsaturated fatty acid) in diets on hedonic feeding behaviors were investigated, and changes of feeding-related protein levels in the brain were detected to explore the possible mechanism underlying the effects of these fatty acids. As a result, mice fed a diet containing stearic acid, compared to a diet containing oleic acid, exhibited increased food intake, hedonic eating, and an operant response to sucrose and locomotor activity. Furthermore, stearic acid corresponded to a higher level of leptin in serum than oleic acid. In addition, the stearic acid treated group had lower protein levels of p-JAK2 and p-STAT3 in the VTA and a higher dopamine concentration in the NAc than the oleic acid-treated group. Meanwhile, the protein level of TH in the NAc was higher and the protein level of the DA transporter in the VTA was lower in the stearic acid-fed group than in the oleic acid-fed group. In conclusion, these findings indicated that a diet containing stearic acid can increase hedonic feeding behavior and affect mesolimbic dopamine system signals in mice. Moreover, the lowering of serum leptin and leptin signaling in the VTA may contribute to this effect.

Introduction

Obesity is currently a worldwide phenomenon. The consumption of calorie-rich foods is responsible for most obesity cases, but not all humans exposed to high-calorie diets develop oleic acid. According to recent studies, the exposure to fat-rich diets maybe the actual cause of obesity. Fats are usually referred to as triglycerides, which are made up of glycerol and fatty acids. It has been reported that dietary long-chain fatty acids affect brain function and are linked to food intake and motivation-related behaviors (Adachi et al., 2013; Figlewicz et al., 2018).

Motivational processes normally modulated by the reward system in the brain overcome physiological hunger and satiety signaling to influence feeding behaviors. Even if animals are not hungry, reward mechanisms will provide the motivation to consume palatable food, particularly those rich in sugars and fats (Volkow et al., 2011). This phenomenon is referred to as hedonic eating (Jager and Witkamp, 2014). Hedonic eating is defined as the intermittent and excessive intake of a large amount of food within a short timeframe (Mitchell and Mussell, 1995; Patrick, 2002). The mesolimbic dopamine (DA) system plays an important role in this process (van Gestel et al., 2014). The mesolimbic DA system is composed of the dopamine neurons of the midbrain ventral tegmental area (VTA) that project into the nucleus accumbens (NAc) striatum and other brain areas to regulate reward and motivational behaviors (Ikemoto and Panksepp, 1996; Kelley et al., 2005; Kelley and Berridge, 2002; Swanson, 1982). It has been shown that DA release significantly increases in the NAc during the consumption of palatable foods (Rada et al., 2005; Valdivia et al., 2015; Wilson et al., 1995). This behavior potently increases the motivation to gain palatable food (Salamone and Correa, 2012). Pharmacological increases in DA signaling in the NAc can enhance an animal’s work for food in an operant lever-pressing reinforcement procedure. Therefore, a food reward is considered to be one of the strongest triggers to start eating (Jager and Witkamp, 2014).

Energy-dense and palatable lipid-rich foods are major determinants of food choices and consumption (Weltens et al., 2014). Indeed, the brain has a dry weight of more than 50 % of its wet weight, which indicates the important role of lipids in signaling pathways (Edmond, 2001; Rapoport, 2001). Lipids—both free fatty acids (FFAs) and triacylglycerols (TAGs)—can also directly interact with the brain (Gomez-Pinilla, 2008; Rasmussen et al., 2012). Thus, fatty acids and their metabolites play important roles in the regulation of the appetite and eating behaviors. It has been established very clearly that medium-chain fatty acids (MCFAs) and odd-chain fatty acids are not linked to appetite regulation (Dasgupta and Bhattacharyya, 2009; Lemarie et al., 2015; Miyagawa et al., 2018; Witkamp, 2018). Long-chain fatty acids (LCFA) can be detected by the central nervous system to control energy homeostasis, and the effect of LCFA on metabolism depends on the structure of the chain.

Several lines of evidence indicate that i.c.v. infusion of oleic acid (OA, a long-chain monounsaturated fatty acid with 18 C) can suppress food intake through regulating the activity of POMC neurons (Coccurello et al., 2010; Jo et al., 2009). Intra-VTA injection of OA blunts the rewarding effects of sucrose (Hryhorczuk et al., 2018), while dietary supplementation with stearic acid (SA, a long-chain saturated fatty acid with 18 C) increases motivation for sucrose in rats in an operant response for sucrose tasks compared with rats on a low-fat diet (Figlewicz et al., 2018). Therefore, this evidence suggests that saturated and unsaturated fatty acids may affect the feeding regulation system differently through the peripheral and central nervous systems. However, it is still not clear whether this effect is due to high fatty acid contents or the fatty acid itself. Meanwhile, the roles of different fatty acids in food reward remain largely undiscovered.

The oil used in chow diets for mice is normally soybean oil, which is mainly composed of oleic acid. To eliminate the effects of other fatty acids in soybean oil, in our control group, soybean oil in the diet was replaced by an equivalent energy value of oleic acid (OA, a monounsaturated fatty acid). A diet containing stearic acid (SA, a saturated fatty acid) was formulated based on an equal caloric density to that of the control. The food reward-related behaviors of mice and the mesolimbic dopamine-related signaling pathway were investigated. We confirmed the different impacts of dietary stearic acid and oleic acid on hedonic feeding, the operant response to sucrose and locomotor activity. Moreover, the possible mechanism of these fatty acid effects was preliminarily explored.

Section snippets

Animals and diets

C57BL6/J male mice were purchased from the Animal Experiment Center of Guangdong Province (Guangzhou, Guangdong, China). All procedures performed on the mice followed the NIH guidelines for animal care and were approved by the Animal Care and Use Committee of South China Agricultural University. This research proposal was approved in November 2018. Animals were 21 days old upon arrival and were housed in single cages under standard conditions at a constant temperature (25 ± 1℃) with light

Dietary stearic acid increased the food intake of mice compared with oleic acid

The diet with stearic acid significantly increased the food intake of mice compared to the diet with oleic acid (Fig. 1B), without changing body weight, lean mass or fat mass (Fig. 1A, 1C and 1D). Two-way ANOVA revealed that there were significant main effects from weeks (F (4, 131) = 13.02, p < 0.0001) and diet (F (1, 131) = 59.10, p < 0.0001) but no significant main effect from the weeks × diet interaction (F (4, 131) = 2.198, p = 0.072).

Mice that were fed stearic acid exhibited increased

Discussion

Our study demonstrates that mice fed stearic acid had increased food intake, hedonic eating, operant response for sucrose and locomotor activity relative to mice fed oleic acid. Meanwhile, the body weight, fat mass and lean mass were not changed, which suggests that the behavioral effects of dietary fatty acids and their actions in the central nervous system are not the result of obesity. Mice fed the SA diet showed higher locomotor activity compared to OA-fed mice, which is probably why they

Conclusion

Dietary stearic acid can increase hedonic feeding behaviors and mesolimbic dopamine system signals in mice. Moreover, decreasing serum leptin and leptin signaling in the VTA may contribute to this effect.

Funding

This work was supported by the National Natural Science Foundation of China (31672464).

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgements

Wang Lina conceived and designed the experiments; Yongxiang Li performed the experiments and analyzed the data; Hanyu Wu and Ruixue Zhang participated in the discussion; Gang Shu, Songbo Wang, Ping Gao, Xiaotong Zhu and Qingyan jiang contributed reagents, materials and analysis tools; Yongxiang Li and Lina Wang wrote the paper. All authors have read and approved the manuscript.

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