N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs. © MDPI AG. All rights reserved.

PURPOSE: Mechanisms related the crosstalk between adipocytes and colon cancer cells are still not clear. We hypothesize that molecules and adipocytokines generated from the adipose tissue of obese individuals accentuate the effect on the metabolic reprogramming in colon cancer cells, i.e. induce disarray in energy metabolism networks of the targeted affected colonic epithelial cells, prompting their malignant phenotype. METHODS: To explore the mechanistic behind this crosstalk we conducted a co-culture model system using human colon cancer cells having different malignant abilities and adipocytes from different depots and subjects. RESULTS: The results demonstrate that co-culturing aggressive colon cancer cells such as HM-7 cells, with Visceral or Subcutaneous adipocytes (VA or SA respectively) from lean/obese subjects significantly up-regulate the secretion of the adipokines IL-8, MCP1, and IL-6 from the adipocytes. Surprisingly, the response of co-culturing HM-7 cells with obese SA was substantially more significant. In addition, these effects were significantly more pronounced when using HM-7 cells as compared to the less malignant HCT116 colon cancer cells. Moreover, the results showed that HM-7 cells, co-cultured with VA or SA from obese subjects, expressed higher levels of fatty acid binding protein 4; thus, the conditioned media obtained from the wells contained HM-7 cells and adipocytes from obese subjects was significantly more efficient in promoting invasion of HM-7 cells. CONCLUSIONS: We conclude that interaction between adipocytes and colon cancer cells, especially the highly malignant cells, results in metabolic alterations in colon cancer cells and in highly hypertrophy phenotype which characterized by increasing adipokines secretion from the adipocytes. © 2019 The Authors

We have recently demonstrated that we could enhance glucan content in Pleurotus eryngii following cultivation of the mushrooms on a substrate containing different concentrations of olive mill solid waste (OMSW). These changes are directly related to the content of OMSW in the growing substrate. Using dextran sulfate sodium (DSS)-inflammatory bowel disease (IBD) mice model, we measured the colonic inflammatory response to the different glucan preparations. We found that the histology damaging score (HDS) resulting from DSS treatment reach a value of 11.8 ± 2.3 were efficiently downregulated by treatment with the fungal extracted glucans. Glucans extracted from stalks cultivated at 20% OMSW downregulated to a HDS value of 6.4 ± 0.5 whereas those cultivated at 80% OMSW showed the strongest effects (5.5 ± 0.6). Similar downregulatory effects were obtained for expression of various intestinal cytokines. All tested glucans were equally effective in regulating the number of CD14/CD16 monocytes from 18.2 ± 2.7% for DSS to 6.4 ± 2.0 for DSS + glucans extracted from stalks cultivated at 50% OMSW. We tested the effect of glucans on lipopolysaccharide- induced production of TNF-α, which demonstrated that stalk-derived glucans were more effective than caps-derived glucans. Isolated glucans competed with anti-Dectin-1 and anti-CR3 antibodies, indicating that they contain β-glucans recognized by these receptors. In conclusion, the most effective glucans in ameliorating IBD-associated symptoms induced by DSS treatment in mice were glucan extracts prepared from the stalk of P. eryngii grown at higher concentrations of OMSW. We conclude that these stress-induced growing conditions may be helpful in selecting more effective glucans derived from edible mushrooms. © 2019 by Begell House, Inc.