Codonopsis pilosula Polysaccharides Alleviate Aβ1–40-Induced PC12 Cells Energy Dysmetabolism via CD38/NAD+ Signaling Pathway

Background: Alzheimer's disease (AD) is the most common type of dementia and has a complex pathogenesis with no effective treatment. Energy metabolism disorders, as an early patho- logical event of AD,have attracted attention as a promising area of AD research. Codonopsis pilo- sula Polysaccharides are the main effective components of Codonopsis pilosula, which have been demonstrated to regulate energy metabolism. Methods: In order to further study the roles and mechanisms of Codonopsis pilosula polysaccharides in AD, this study used an Aβ1–40-induced PC12 cells model to study the protective effects of Codonopsis pilosula polysaccharides and their potential mechanisms in improving energy metabolism dysfunction. Results: The results showed that Aβ1–40 induced a decrease in PC12 cells viability, energy metabolism molecules (ATP, NAD+, and NAD+/NADH) and Mitochondrial Membrane Potential (MMP) and an increase in ROS. Additionally, it was found that Aβ1–40 increased CD38 expres- sion related to NAD+ homeostasis, whereas Silent Information Regulation 2 homolog1 (SIRT1), SIRT3, Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) and SIRT3 activity were decreased. Codonopsis pilosula polysaccharides increased NAD+, NAD+/NADH, SIRT3, SIRT1, and PGC-1α related to NAD+, thus partially recovering ATP. Conclusions: Our findings reveal that Codonopsis pilosula polysaccharides protected PC12 cells from Aβ1–40-induced damage, suggesting that these components of the Codonopsis pilosula herb may represent an early treatment option for AD patients.

Gut microbiota as risk factor causing obesity in children

Nowadays obesity resulting from abnormal or excessive fat deposits in a body has become a true epidemic. Risk factors that cause the disease include improper lifestyle, hereditary predisposition, as well as metabolic activity of gut microbiota. Research works performed over the last decades indicate that microbes that create colonies in human intestines play a significant role in maintaining proper metabolism. There is a correlation between disorders in gut microbiota structure and immune disorders, elevated susceptibility to infections, and obesity. There is more and more evidence that gut microbiota and its overall bacterial genome exert their influence on nutrients assimilation and regulate energy metabolism and fat accumulation. Certain differences were detected in microbiota gut structure in children and adults with obesity and people with proper body mass index. Delivery and feeding are among key factors influencing gut microbiota formation in a child. Thus, research results indicate that natural birth, as opposed to cesarean section, can prevent obesity occurrence in a child. Breast-feeding also makes a substantial contribution into development of an infant since breast milk is balanced food that provides optimal metabolism in an infant’s body and helps creating proper gut microbiota. At the same time, according to data obtained via numerous research works, artificial feeding can be related to obesity occurrence in future. Ways to fight obesity include medication therapy, dietary nutrition, physical activity as well as bariatric surgery; the latter is nowadays considered to be the most efficient procedure on the matter. Reduction in body mass via influencing gut microbiota is a promising trend in research in the sphere. Despite there are objective data on benign effects produced by probiotics and prebiotics on gut microbiota, experts haven’t been able to reach agreement on their efficiency yet.

Gut microbiota as risk factor causing obesity in children

Nowadays obesity resulting from abnormal or excessive fat deposits in a body has become a true epidemic. Risk factors that cause the disease include improper lifestyle, hereditary predisposition, as well as metabolic activity of gut microbiota. Research works performed over the last decades indicate that microbes that create colonies in human intestines play a significant role in maintaining proper metabolism. There is a correlation between disorders in gut microbiota structure and immune disorders, elevated susceptibility to infections, and obesity. There is more and more evidence that gut microbiota and its overall bacterial genome exert their influence on nutrients assimilation and regulate energy metabolism and fat accumulation. Certain differences were detected in microbiota gut structure in children and adults with obesity and people with proper body mass index. Delivery and feeding are among key factors influencing gut microbiota formation in a child. Thus, research results indicate that natural birth, as opposed to cesarean section, can prevent obesity occurrence in a child. Breast-feeding also makes a substantial contribution into development of an infant since breast milk is balanced food that provides optimal metabolism in an infant’s body and helps creating proper gut microbiota. At the same time, according to data obtained via numerous research works, artificial feeding can be related to obesity occurrence in future. Ways to fight obesity include medication therapy, dietary nutrition, physical activity as well as bariatric surgery; the latter is nowadays considered to be the most efficient procedure on the matter. Reduction in body mass via influencing gut microbiota is a promising trend in research in the sphere. Despite there are objective data on benign effects produced by probiotics and prebiotics on gut microbiota, experts haven’t been able to reach agreement on their efficiency yet.

Maternal Intake Restriction Programs the PKA-CREB Pathway to Regulate Energy Metabolism, CLOCK and mTOR Signals in the Skeletal Muscles of Goat Offspring

BackgroundThe biological mechanism about that maternal undernutrition increases the metabolic disorder risk of skeletal muscles in offspring is less known. We hypothesize that maternal intake restriction influences metabolic signals in the skeletal muscles of offspring via a glucagon-mediated pathway. Twenty-four pregnant goats were assigned to the control (100% of the nutrients requirement) and restricted (60% of the control from pregnant days of 45 to 100) groups. Blood and longissimus thoracis muscle were sampled from dams, fetuses and kids in each group.ResultsIntake restriction reduced the total blood protein of dams and fetuses. Maternal restriction decreased the CREB1, CREBBP, PKA, BMAL1, AKT1, mTOR, and RPTOR mRNA expressions in the fetuses, reduced the CREBBP, NR1H3, DBP and PKA mRNA levels in the kids, but increased the PGC1α and TSC2 mRNA levels in the fetuses, while the mRNA expression of CLOCK and TSC2 genes was increased in the restricted kids. The protein expression of total PKA and phosphorylated PKA of the restricted fetuses and kids were downregulated, while the protein expression of total mTOR and phosphorylated mTOR were reduced in the restricted fetuses and kids. ConclusionsMaternal intake restriction regulated fat oxidation, protein synthesis, and circadian clock expression in the muscles of the offspring via the glucagon-mediated PKA-CREB pathway, which reveals a molecular pathway that maternal undernutrition leads to metabolic adaptation of skeletal muscle in offspring.

The Impact of Bone on the Biology of Aging

We hypothesized that bone may secrete hormones that regulate energy metabolism and reproduction. Testing this hypothesis revealed that the osteoblast-specific secreted protein osteocalcin is a hormone regulating glucose homeostasis and male fertility by signaling through a GPCR, Gprc6a, expressed in pancreatic β bells and Leydig cells of the testes. The systematic exploration of osteocalcin biology, revealed that it regulates an unexpectedly large spectrum of physiological functions in the brain and peripheral organs and that it has most features of an antigeromic molecule. As will be presented at the meeting, this body of work suggests that harnessing osteocalcin for therapeutic purposes may be beneficial in the treatment of age-related diseases such as depression, age-related memory loss and the decline in muscle function seen in sarcopenia.

“The Loss of Golden Touch”: Mitochondria-Organelle Interactions, Metabolism, and Cancer

Mitochondria represent the energy hub of cells and their function is under the constant influence of their tethering with other subcellular organelles. Mitochondria interact with the endoplasmic reticulum, lysosomes, cytoskeleton, peroxisomes, and nucleus in several ways, ranging from signal transduction, vesicle transport, and membrane contact sites, to regulate energy metabolism, biosynthetic processes, apoptosis, and cell turnover. Tumorigenesis is often associated with mitochondrial dysfunction, which could likely be the result of an altered interaction with different cell organelles or structures. The purpose of the present review is to provide an updated overview of the links between inter-organellar communications and interactions and metabolism in cancer cells, with a focus on mitochondria. The very recent publication of several reviews on these aspects testifies the great interest in the area. Here, we aim at (1) summarizing recent evidence supporting that the metabolic rewiring and adaptation observed in tumors deeply affect organelle dynamics and cellular functions and vice versa; (2) discussing insights on the underlying mechanisms, when available; and (3) critically presenting the gaps in the field that need to be filled, for a comprehensive understanding of tumor cells’ biology. Chemo-resistance and druggable vulnerabilities of cancer cells related to the aspects mentioned above is also outlined.

Bile acid metabolism and circadian rhythms

Circadian rhythms are biological systems that synchronize cellular circadian oscillators and regulate nutrient absorption and utilization. Bile acids are important modulators that facilitate nutrient absorption and regulate energy metabolism. Bile acid metabolism and circadian rhythms are related to metabolic diseases, and their intersections have not been summarized clearly up to now. This review summarizes the molecular association between circadian rhythms and bile acid metabolism and points out future perspectives and potential therapeutic targets in metabolic diseases.