Humanin suppresses receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via AMP-activated protein kinase activation

Humanin (HN) is a mitochondrial peptide that exhibits cytoprotective actions against various stresses and diseases. HN has been shown to induce the phosphorylation of AMP-activated protein kinase (AMPK), which is a negative regulator of receptor activator of nuclear factor-κB ligand (RANKL). However, the role of HN in osteoclastogenesis or other skeletal disorders remains unknown. Here, we examined whether HN regulates osteoclastogenesis via AMPK activation using bone marrow-derived macrophage (BMM) cultures. Our results show that HN inhibited RANKL-induced osteoclast formation and reduced the expression of genes involved in osteoclastogenesis, including nuclear factor of activated T-cells cytoplasmic 1, osteoclast-associated receptor, cathepsin K, and tartrate-resistant acid phosphatase. Moreover, HN increased the levels of phosphorylated AMPK protein; compound C, an AMPK inhibitor, recovered HN-induced osteoclast differentiation. In addition, we found that HN significantly decreased the levels of RANKL-induced reactive oxygen species in BMMs. Therefore, these results indicate that HN plays an important role in osteoclastogenesis and may function as an inhibitor of bone disorders via AMPK activation.

4-hydroxy-3-methoxycinnamic acid regulates orexigenic peptides and hepatic glucose homeostasis through phosphorylation of FoxO1

4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) is known to have numerous beneficial health effects, including anti-obesity and anti-hyperglycemic properties. However, the molecular networks that modulate the beneficial FA-induced metabolic effects have not been well elucidated. In this study, we explored the molecular mechanisms mediating the beneficial metabolic effects of FA. In mice, FA protected against high-fat diet-induced weight gain, reduced food intake and exhibited an overall improved metabolic phenotype. The food intake suppression by FA was accompanied by a specific reduction in hypothalamic orexigenic neuropeptides, including agouti-related protein and neuropeptide Y, with no significant changes in the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-regulated transcript. FA treatment also inhibited fat accumulation in the liver and white adipose tissue and suppressed the expression of gluconeogenic genes, including phosphoenolpyruvate carboxylase and glucose-6-phosphatase. Furthermore, we show that FA phosphorylated and inactivated the transcription factor FoxO1, which positively regulates the expression of gluconeogenic and orexigenic genes, providing evidence that FA might exert its beneficial metabolic effects through inhibition of FoxO1 function in the periphery and the hypothalamus.

Serum Fibroblast Growth Factor 21 and New-Onset Metabolic Syndrome: KoGES-ARIRANG Study

PURPOSE: Fibroblast growth factor 21 (FGF21) is a crucial metabolic regulator, with multiple favorable effects on glucose homeostasis and lipid metabolism. Since serum FGF21 level has been implicated as a potential marker for the early identification of metabolic syndrome (MetS), we investigated the association between serum FGF21 level and the development of MetS in a population-based prospective study. MATERIALS AND METHODS: We conducted a prospective study of 221 randomly sampled adults without MetS from a general population-based cohort study who were examined from 2005–2008 (baseline) and from 2008–2011 (follow-up). Baseline serum FGF21 levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: During the average 2.8-year follow-up period, 82 participants (36.6%) developed new-onset MetS. Serum FGF21 levels were significantly higher in patients with new-onset MetS than in those without MetS (209.56±226.80 vs. 110.09±81.10, p < 0.01). In multivariate adjusted models, the odds for MetS development were greater in patients with serum FGF21 levels in the highest quartile, compared to those in the lowest quartile (3.84, 95% confidence interval: 1.59–9.28). CONCLUSION: Serum FGF21 level was an independent predictor for new-onset MetS in a population-based prospective study.

Ultrastructures of Colletotrichum orbiculare in the Leaves of Cucumber Plants Expressing Induced Systemic Resistance Mediated by Glomus intraradices BEG110

The colonization of an arbuscular mycorrhizal fungus Glomus intraradices BEG110 in the soil caused a decrease in disease severity in cucumber plants after fungal inoculation with Colletotrichum orbiculare. In order to illustrate the resistance mechanism mediated by G. intraradices BEG110, infection patterns caused by C. orbiculare in the leaves of cucumber plants and the host cellular responses were characterized. These properties were characterized using transmission electron microscopy on the leaves of cucumber plants grown in soil colonized with G. intraradices BEG110. In the untreated plants, inter- and intra-cellular fungal hyphae were observed throughout the leaf tissues during both the biotrophic and necrotrophic phases of infection. The cytoplasm of fungal hyphae appeared intact during the biotrophic phase, suggesting no defense response against the fungus. However, several typical resistance responses were observed in the plants when treated with G. intraradices BEG110 including the formation of sheaths around the intracellular hyphae or a thickening of host cell walls. These observations suggest that the resistance mediated by G. intraradices BEG110 most often occurs in the symplast of the host cells rather than in the apoplast. In addition, this resistance is similar to those mediated by biotic inducers such as plant growth promoting rhizobacteria.