Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral region of the paraventricular hypothalamus (PVH) induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism. These neurons manifest activation of AMP-activated protein kinase (AMPK) during food deprivation, and this activation is necessary and sufficient for selection of an HCD over an HFD. Furthermore, this effect is mediated by carnitine palmitoyltransferase 1c (CPT1c). Thus, our results identify the specific neurons and intracellular signaling pathway responsible for regulation of the complex behavior of selection between an HCD and an HFD. VIDEO ABSTRACT.
Background Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice. Methods Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method. Results The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice. Conclusions These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.
Background and Aim: Myanmar is one of the countries in production of agricultural plant commodities. Nowadays, pesticides are commonly used to increase agricultural production and productivity. Organophosphate pesticides exposure can cause many physiological changes within the body including impaired respiratory function. Therefore, the present study aimed to find out the relationship between the erythrocyte acetylcholinesterase enzyme activity, serum interleukin-6 level and respiratory functions such as forced expiratory volume in first second (FEV1), forced vital capacity (FVC), ratio of forced expiratory volume in first second and forced vital capacity (FEV1/FVC), peak expiratory flow (PEF) and average forced expiratory flow between 25% and 75% of FVC (FEF25-75%) among agricultural workers who exposed to organophosphate pesticides and non-exposed control subjects. Methods: A community-based cross-sectional, comparative study was done in agricultural workers (n = 40) who live in A-lal-chaung village, Magway Township and age/BMI matched non-exposed subjects (n = 40) who live in Yan-Way Quarter, Magway Township. All the participants were selected according to inclusion and exclusion criteria by simple random sampling method. Erythrocyte acetylcholinesterase (AchE) enzyme activity was measured by spectrophotometric method and serum interleukin-6 levels were measured by enzymelinked immunosorbent assay (ELISA) method. Respiratory function parameters were measured by Spirobank II spirometer. Results: The mean erythrocyte acetylcholinesterase enzyme activity was significantly lower in exposed group than that of non-exposed group (3354.43±589.81 U/L vs 4515.83±759.33 U/L; p<0.001). The percentage of predicted value of respiratory function parameters of exposed group were significantly lower than that of non-exposed group (FEV1: 72.13±4.40 vs 75.95±4.05; FVC: 66.90±4.40 vs 70.60±4.20; FEV1/FVC: 110.35±2.69 vs 111.32±1.33; PEF: 5.52±8.66 vs 79.40±5.09) (p<0.05). There were significant positive correlation between erythrocyte acetylcholinesterase activity and respiratory function parameters in all groups (n=80) (FEV1: r=0.425, p<0.001; FVC: r=0.301, p<0.05 and PEF: r=0.316, p<0.05). There were significant negative correlation between erythrocyte acetylcholinesterase activity and serum IL-6 level (r=-0.374, n= 80, p<0.05). Serum IL-6 level was significantly higher in exposed group than non-exposed group (34.77±3.3 pg/mL vs 28.75±2.0 pg/mL; p <0.001). There was a significant negative correlation between serum IL-6 level and respiratory function parameters in all group (n=80) such as FEV1 (r= 0.300, p<0.05) and FVC (r= 0.331, p<0.05). Conclusion: It was concluded that agricultural workers who exposed to organophosphate pesticides have higher serum IL-6 level and lower respiratory functions than that of non-exposed subjects. The present findings highlighted that there has an impact of chronic low dose OP exposure on respiratory health and there has a role of IL-6 in respiratory function decline.
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