Sodium butyrate protects against oxidative stress in high-fat-diet-induced obese rats by promoting GSK-3ß/Nrf2 signaling pathway and mitochondrial function.

Sodium butyrate (NaB), obtained by fermenting dietary fiber via intestinal microflora, was recently shown to improve the activity of some antioxidant enzymes in vivo. This study aims to investigate the term changes of mitochondrial energy metabolism and redox homeostasis in skeletal muscles and clarify the regulatory mechanism and dose effect of NaB on skeletal muscle. Male Sprague-Dawley rats were divided into the control group, obesity-prone (OP) group and obesity-resistant (OR) group based on the gain of body weight after 8 weeks' of feeding high-fat diet (HFD), followed by sacrificing rats at the end of 20th week. NaB intervention (12 weeks) could effectively reduce the body weight of rats in the OP and OR groups. NaB also mediated upregulation of antioxidant enzyme activity and GSH/GSSG ratio, while reducing reactive oxygen species (ROS) levels and malondialdehyde (MDA) content. At the molecular level, NaB upregulated Pi3k, Nrf2, Nqo-1, and Ho-1, but downregulated Gsk-3ß mRNA expression by regulating the Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention significantly upregulated Glut4, Irs-1, Pdx1, and MafA, expression in gastrocnemius muscles of OP and OR rats, and elevated insulin secretion and muscle insulin sensitivity. Thus, NaB activates antioxidant pathway, improves the antioxidant capacity of obese rat tissues and promotes glucose metabolism. PRACTICAL APPLICATIONS: This study found that obesity-prone and obesity-resistant rats have differences in mitochondrial redox homeostasis and energy metabolism in tissues. Meanwhile, sodium butyrate can effectively promote muscle protein synthesis, increase insulin sensitivity, and promote glucose metabolism in obesity rats. Thus, sodium butyrate supplementation or increasing intestinal butyrate production (e.g., by consuming foods rich in dietary fiber) is a potential means of improving the body's glucose metabolism and obesity profile.

Vegetation History and Survival Patterns of the Earliest Village on the Qinghai-Tibetan Plateau.

The upper Yellow River valley in the northeastern Qinghai-Tibetan Plateau (QTP) is an important corridor for prehistoric migration to the hinterland plateau. However, most studies have focused on the Neolithic Age, with limited evidence for earlier periods. The Shalongka (SLK) site on the northeastern QTP spans the Epipaleolithic to Bronze Age and contains cultural deposits, so provides a good basis for unraveling the evolutionary history of the human-land relationship. In this study, we sampled the 420-cm-thick section T1406E at the SLK site and undertook lithologic stratigraphic description and analysis of grain size, redness, magnetic susceptibility, geochemical elements, pollen and charcoal. Dating control was provided by accelerated mass spectrometry 14C and optically stimulated luminescence methods. Results show that SLK site was affected by the local fluvial sedimentary environment. The absolute dating results of the SLK site have revealed that humans occupied the site during the Epipaleolithic (8.5-7.3 cal ka BP), Yangshao culture (5.9-5.1 ka) and Qijia Culture (4.1-3.9 cal ka BP). Pollen analysis showed that the humans lived in a landscape that was predominated by forest-steppe. Consolidating with multidisciplinary evidence, we learned that Epipaleolithic sites were occupied by microlithic hunter-gatherers and comprised by relatively fixed seasonal central campsites, and their mobility was significantly decreased from the early to late period. Subsequently, farmers of the Yangshao culture migrated from the low elevation (Chinese Loess Plateau) to the upper Yellow River valleys on the QTP and founded the earliest settlement villages (~5.9 ka) on the QTP. People of the Qijia culture adopted diversified survival strategies under the settled lifestyle. In all, we infered that SLK site may play an important role in the communication and integration between different people and cultures.

Differences in energy metabolism and mitochondrial redox status account for the differences in propensity for developing obesity in rats fed on high-fat diet.

Obesity is a metabolic disease that is accompanied by oxidative stress. Mitochondrial dysfunction is closely associated with the occurrence and development of obesity. However, it is unclear if there are differences in mitochondrial redox homeostasis and energy metabolism between obesity-prone (OP) and obesity-resistant (OR) individuals and if these differences account for the different susceptibilities to developing obesity. The present study aimed to compare the regulation of energy metabolism between OP and OR rats during high-fat diet (HFD)-induced oxidative stress. Male Sprague Dawley rats were randomly divided into the control group and the HFD group. The HFD group was further divided into the OP and OR groups based on body weight gain (upper 1/3 for OP; lower 1/3 for OR) after eight weeks on HFD. Rats were sacrificed at the 8th and 20th week, and serum and organs were collected. At 8 weeks, HFD decreased mitochondrial antioxidant enzyme activity and increased the production of ROS in the OP rats, which was accompanied by unusual mitochondrial oxidative phosphorylation, reduced mitochondrial membrane potential (MMP), and decreased ATP production. When the feeding period was extended beyond the 8 weeks, the energy expenditure of the OP rats reduced further, resulting in elevated blood lipids and glucose levels and increased body weight. In contrast, the OR rats had higher mitochondrial antioxidant enzyme activity and normal redox homeostasis throughout the period, which was beneficial in energy utilization and ATP production. Thus, the increase in energy expenditure in the OR rats reduced the HFD-induced weight gain. Mitochondrial function and antioxidant defense might be involved in the different propensities for developing obesity. Consequently, the ability of OR rats to resist obesity may be attributed to their ability to maintain mitochondrial function and redox balance.

Evaluating the Activity of Sodium Butyrate to Prevent Osteoporosis in Rats by Promoting Osteal GSK-3ß/Nrf2 Signaling and Mitochondrial Function.

Oxidative stress (OS) and mitochondrial dysfunction are key pathophysiological features of osteoporosis and obesity. Sodium butyrate (NaB), produced by fermentation by the gut microbiota of the large intestine, has been demonstrated to protect against OS by improving specific antioxidant enzymes and to regulate mitochondria redox homeostasis in vivo. Here, in an unblinded study, we identified femur mitochondria as the main target of the beneficial effects of NaB, consisting of reversion of bone loss and body-weight gain in obesity-prone rats. In particular, NaB promoted the activity of mitochondrial antioxidant enzymes and energy metabolism, preserved the bone microstructure and calcium homeostasis, and activated bone metabolism, as shown by increased Nrf2/GSK-3ß signaling and the upregulation of PGC-1α and TFAM. In vitro experiments showed that moderate NaB treatment prevented H2O2-induced oxidative damage in MC3T3-E1 cells, improved osteoblast mineralization and differentiation, and maintained the balance in bone metabolism by enhancing intracellular antioxidant enzyme activity and ATP production and decreasing the ROS level. In conclusion, NaB promoted the Nrf2/GSK-3ß signaling pathway and mitochondrial function and is a potential new therapeutic strategy for obesity and osteoporosis.

Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function

Sodium butyrate (NaBu) is a by-product of microbial fermentation of dietary fiber in the gastrointestinal tract and has been shown to increase the activity of antioxidant enzymes, such as catalase or heme oxidase-1, in vivo. However, the mechanism of this effect is still unclear. This study investigated the antioxidant effect of NaBu on HepG2 cells under H2O2-induced oxidative stress. NaBu (0.3 mM) attenuated cell death and accumulation of reactive oxygen species and improved multiple antioxidant parameters in H2O2-injured HepG2 cells. NaBu inhibited glycogen synthase kinase-3 beta (GSK-3Beta) by increasing the p-GSK-3 Beta (Ser9) level and promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increased the expression of downstream antioxidant enzymes. Together with promotion of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial DNA copy number, NaBu modulated energy metabolism and mitochondrial function, decreasing glycolysis, increasing Beta -oxidation, and enhancing the tricarboxylic acid cycle and oxidative phosphorylation. NaBu increased mitochondrial manganese-superoxide dismutase and glutathione peroxidase activity. In conclusion, NaBu protected HepG2 cells against oxidative stress by modulating Nrf2 pathway activity and mitochondrial function

Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function.

Sodium butyrate (NaBu) is a by-product of microbial fermentation of dietary fiber in the gastrointestinal tract and has been shown to increase the activity of antioxidant enzymes, such as catalase or heme oxidase-1, in vivo. However, the mechanism of this effect is still unclear. This study investigated the antioxidant effect of NaBu on HepG2 cells under H2O2-induced oxidative stress. NaBu (0.3 mM) attenuated cell death and accumulation of reactive oxygen species and improved multiple antioxidant parameters in H2O2-injured HepG2 cells. NaBu inhibited glycogen synthase kinase-3 beta (GSK-3ß) by increasing the p-GSK-3ß (Ser9) level and promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), which increased the expression of downstream antioxidant enzymes. Together with promotion of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial DNA copy number, NaBu modulated energy metabolism and mitochondrial function, decreasing glycolysis, increasing ß-oxidation, and enhancing the tricarboxylic acid cycle and oxidative phosphorylation. NaBu increased mitochondrial manganese-superoxide dismutase and glutathione peroxidase activity. In conclusion, NaBu protected HepG2 cells against oxidative stress by modulating Nrf2 pathway activity and mitochondrial function.

Influence of autapse on mode-locking structure of a Hodgkin-Huxley neuron under sinusoidal stimulus.

We investigated the mode-locking behaviors of a Hodgkin-Huxley neuron with an autapse under sinusoidal stimulus. A neuron without an autapse can exhibit rich p:q mode-locking (i.e. p output action potentials generated by q cycles stimulations) behaviors with periodic stimuli. In the presence of the autaptic connection, the p:q mode-locking behaviors are completely reset. The autapse extends the scope of mode-locking. The autapse can enhance or suppress the status of mode-locking. Even for some specified autaptic parameters, the neuron could be driven into the sub-threshold oscillation. Our results suggested that the autapse can serve as a potential control option for adjusting the mode-locking firing behaviors. We also found that changing the delay time is much more effectively operable to regulate the response behavior than the autaptic intensity.

amoA-encoding archaea and thaumarchaeol in the lakes on the northeastern Qinghai-Tibetan Plateau, China.

All known ammonia-oxidizing archaea (AOA) belong to the phylum Thaumarchaeota within the domain Archaea. AOA possess the diagnostic amoA gene (encoding the alpha subunit of ammonia monooxygenase) and produce lipid biomarker thaumarchaeol. Although the abundance and diversity of amoA gene-encoding archaea (AEA) in freshwater lakes have been well-studied, little is known about AEA ecology in saline/hypersaline lakes. In this study, the distribution of the archaeal amoA gene and thaumarchaeol were investigated in nine Qinghai-Tibetan lakes with a salinity range from freshwater to salt-saturation (salinity: 325 g L(-) (1)). The results showed that the archaeal amoA gene was present in hypersaline lakes with salinity up to 160 g L(-) (1). The archaeal amoA gene diversity in Tibetan lakes was different from those in other lakes worldwide, suggesting Tibetan lakes (high elevation, strong ultraviolet, and dry climate) may host a unique AEA population of different evolutionary origin from those in other lakes. Thaumarchaeol was present in all of the studied hypersaline lakes, even in those where no AEA amoA gene was observed. Future research is needed to determine the ecological function of AEA and possible sources of thaumarchaeol in the Qinghai-Tibetan hypersaline lakes.