Environmental temperature remarkably impacts on metabolic homeostasis, raising a serious concern about the optimum housing temperature for translational studies. Recent studies suggested that mice should be housed slightly below their thermoneutral temperature (26°C). On the other hand, the external temperature, also known as a zeitgeber, can reset the circadian rhythm. However, whether housing temperature affects the circadian oscillators of the liver remains unknown. Therefore, we have compared the effect of two housing temperatures, namely 21°C (conventional; TC) and 26°C (thermoneutral; TN), on the circadian rhythms in mice. We found that the rhythmicity of food intake showed an advanced phase at TC, while the activity was more robust at TN, with a prolonged period onset. The serum levels of norepinephrine were remarkably induced at TC, but failed to oscillate rhythmically at both temperatures. Likewise, circulating glucose levels were increased but were non-rhythmic under TC. Both total cholesterol and triglycerides levels were induced at TN, but showed an advanced phase under TC. Additionally, the expression of hepatic metabolic genes and clock genes remained rhythmic at both temperatures, with the exception of G6Pase, Fasn, Cpt1a and Cry2, at TN. Nevertheless, the liver histology examination did not show any significant changes in response to housing temperature. Although the non-consistent trends of phase changes in each temperature, our results suggest a non-reductant role of temperature in mouse internal rhythmicity resetting. Thus, the temperature-controlled internal circadian synchronization within organs should be taken into consideration when optimizing housing temperature for mice.
Anjara Rabearivony, Huan Li, Shiyao Zhang, Siyu Chen, Xiaofei An, and Chang Liu
Qiong You, Zijun Wu, Bin Wu, Chang Liu, Ruina Huang, Li Yang, Runmin Guo, Keng Wu, and Jingfu Chen
We previously reported that naringin (NRG) protects cardiomyocytes against high glucose (HG)-induced injuries by inhibiting the MAPK pathway. The aim of this study was to test the hypothesis that NRG prevents cardiomyocytes from hyperglycemia-induced insult through the inhibition of the nuclear factor kappa B (NF-κB) pathway and the upregulation of ATP-sensitive K+ (KATP) channels. Our results showed that exposure of cardiomyocytes to HG for 24h markedly induced injuries, as evidenced by a decrease in cell viability and oxidative stress, and increases in apoptotic cells as well as the dissipation of mitochondrial membrane potential (MMP). These injuries were markedly attenuated by the pretreatment of cells with either NRG or pyrrolidine dithiocarbamate (PDTC) before exposure to HG. Furthermore, in streptozotocin (STZ)-induced diabetic rats and in HG-induced cardiomyocytes, the expression levels of caspase-3, bax and phosphorylated (p)-NF-κB p65 were increased. The increased protein levels were ameliorated by pretreatment with both NRG and PDTC. However, the expression levels of bcl-2 and KATP and superoxide dismutase (SOD) activity were decreased by hyperglycemia; the expression level of Nox4 and the ADP/ATP ratio were increased by hyperglycemia. These hyperglycemia-induced indexes were inhibited by the pretreatment of cardiomyocytes with NRG or PDTC. In addition, in STZ-induced diabetic rats, we also observed that NRG or PDTC contributed to protecting mitochondrial injury and myocardium damage. This study demonstrated that NRG protects cardiomyocytes against hyperglycemia-induced injury by upregulating KATP channels in vitro and inhibiting the NF-κB pathway in vivo and in vitro.
Dong-Xu Han, Chang-Jiang Wang, Xu-Lei Sun, Jian-Bo Liu, Hao Jiang, Yan Gao, Cheng-Zhen Chen, Bao Yuan, and Jia-Bao Zhang
Circular RNAs (circRNAs) are a new class of RNA that have a stable structure characterized by covalently closed circular molecules and are involved in invasive pituitary adenomas and recurrent clinically nonfunctioning pituitary adenomas. However, information on circRNAs in the normal pituitary, especially in rats, is limited. In this study, we identified 4123 circRNAs in the immature (D15) and mature (D120) rat anterior pituitary using the Illumina platform, and 32 differentially expressed circRNAs were found. A total of 150 Gene Ontology terms were significantly enriched, and 16 KEGG pathways were found to contain differentially expressed genes. Moreover, we randomly selected eight highly expressed circRNAs and detected their relative expression levels in the mature and immature rat pituitary by qPCR. In addition, we predicted 90 interactions between 53 circRNAs and 57 miRNAs using miRanda. Notably, circ_0000964 and circ_0001303 are potential miRNA sponges that may regulate the Fshb gene. The expression profile of circRNAs in the immature and mature rat anterior pituitary may provide more information about the roles of circRNAs in the development and reproduction in mammals.
Michael Mangubat, Kabirullah Lutfy, Martin L Lee, Laura Pulido, David Stout, Richard Davis, Chang-Sung Shin, Meghdi Shahbazian, Stephen Seasholtz, Amiya Sinha-Hikim, Indrani Sinha-Hikim, Laura E O'Dell, Alexei Lyzlov, Yanjun Liu, and Theodore C Friedman
Nicotine induces weight loss in both humans and rodents consuming a regular diet; however, the effect of nicotine on body weight and fat composition in rodents consuming a high-fat diet (HFD) has not been well studied. Thus, this study examined the effect of nicotine vs saline on body weight and fat composition in mice fed with either an HFD (62% of kcal from fat) or a standard normal chow diet (NCD) for 7 weeks. Nicotine dose dependently reduced body weight gain in mice that consumed both diets, but this effect was significantly greater in mice on the HFD. Caloric intake was decreased in nicotine-treated mice. Estimates of energy intake suggested that decreased caloric intake accounted for all the reduced weight gain in mice on an NCD and 66% of the reduced weight gain on an HFD. Computed tomography analysis for fat distribution demonstrated that nicotine was effective in reducing abdominal fat in mice that consumed the HFD, with nicotine treatment leading to lower visceral fat. The effect of nicotine on weight loss in mice on an HFD was completely blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor (nAChR) antagonist, but only partially blocked by the α4β2 nAChR partial agonist/antagonist, varenicline. We conclude that nicotine is effective in preventing HFD-induced weight gain and abdominal fat accumulation.
Mingjuan Deng, Fang Qu, Long Chen, Chang Liu, Ming Zhang, Fazheng Ren, Huiyuan Guo, Hao Zhang, Shaoyang Ge, Chaodong Wu, and Liang Zhao
This study aimed to assess the effects of three major SCFAs (acetate, propionate, and butyrate) on NASH phenotype in mice. C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet and treated with sodium acetate, sodium propionate, or sodium butyrate during the 6-week feeding period. SCFA treatment significantly reduced serum levels of alanine aminotransferase and aspartate transaminase, the numbers of lipid droplets, and the levels of triglycerides and cholesterols in livers of the mice compared with control treatment. SCFAs also reduced MCD-induced hepatic aggregation of macrophages and proinflammatory responses. Among the three SCFAs, sodium acetate (NaA) revealed the best efficacy at alleviating MCD-induced hepatic steatosis and inflammation. Additionally, NaA increased AMP-activated protein kinase activation in the liver and induced the expression of fatty acid oxidation gene in both the liver and cultured hepatocytes. In vitro, NaA decreased MCD-mimicking media-induced proinflammatory responses in macrophages to a greater extent than in hepatocytes. These results indicated that NaA alleviates steatosis in a manner involving AMPK activation. Also, NaA alleviation of hepatic inflammation appears to be due to, in large part, suppression of macrophage proinflammatory activation. SCFAs may represent as a novel and viable approach for alleviating NASH.