Impaired leptin responsiveness in the nucleus accumbens of leptin-overexpressing transgenic mice with dysregulated sucrose and lipid preference independent of obesity. (April 2022)

• Record Type: Journal Article
• Authors: Nomura, Hidenari; Son, Cheol; Aotani, Daisuke; Shimizu, Yoshiyuki; Katsuura, Goro; Noguchi, Michio; Kusakabe, Toru; Tanaka, Tomohiro; Miyazawa, Takashi; Hosoda, Kiminori; Nakao, Kazuwa
• Is Part Of: Neuroscience research. Volume 177(2022)
• Page Start: 94
• Page End: 102
• Publication Date: 2022-04
• Subjects: ANOVA analysis of variance -- Arc arcuate nucleus -- CD chow diet -- DMH dorsomedial hypothalamic nucleus -- DIO diet-induced obesity -- HFD high-fat diet -- CA1-3 hippocampal cornu Ammonis -- NAc nucleus accumbens -- NTS nucleus tractus solitarius -- LH lateral hypothalamus -- Lep Tg leptin transgenic -- PFA paraformaldehyde -- pSTAT3 phosphorylated signal transducer and activator of transcription 3 -- VMH ventromedial hypothalamic nucleus -- SE standard error -- VTA ventral tegmental area -- WT wild type; Leptin resistance -- Sucrose and lipid preference -- Nucleus accumbens -- Independently of obesity -- Hypothalamus -- Immunostaining; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2021.12.007
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: LepTg-HFD1W mice showed decreased leptin response in nucleus accumbens independently of obesity. These mice exhibited dysregulated sucrose and lipid preference by leptin without obesity. Decreased leptin response in NAc may contribute to dysregulated hedonic feeding without obesity. Abstract: While hypothalamic leptin resistance can occur prior to establishment of obesity, clarification is needed as to whether the impaired response to leptin in the reward-related nuclei occurs independently of obesity. To answer this question, we attempted to dissociate the normally coexisting leptin resistance from obesity. We investigated phenotypes of leptin-overexpressing transgenic mice fed for 1 week with 60 % high-fat diet (HFD) (LepTg-HFD1W mice). After 1 week, we observed that LepTg-HFD1W mice weighed as same as wild type (WT) mice fed standard chow diet (CD) for 1 week (WT-CD1W mice). However, compared to WT-CD1W mice, LepTg-HFD1W mice exhibited attenuated leptin-induced anorexia, decreased leptin-induced c-fos immunostaining in nucleus accumbens (NAc), one of important site of reward system, decreased leptin-stimulated pSTAT3 immunostaining in hypothalamus. Furthermore, neither sucrose nor lipid preference was suppressed by leptin in LepTg-HFD1W mice. On the contrary, leptin significantly suppressed both preferences in WT mice fed HFD (WT-HFD1 W mice). These results indicate that leptin responsiveness decreases in NAc independently of obesity. Additionally, in this situation, suppressive effect of leptin on the hedonic feeding results in impaired regulation. Such findings suggest the impaired leptin responsiveness in NAc partially contributes to dysregulated hedonic feeding behavior independently of obesity.