Phoenixin-14 stimulates differentiation of 3T3-L1 preadipocytes via cAMP/Epac-dependent mechanism

Phoenixin-14 (PNX) is a newly discovered peptide produced by proteolytic cleavage of the small integral membrane protein 20 (Smim20). Previous studies showed that PNX is involved in controlling reproduction, pain, anxiety and memory. Furthermore, in humans, PNX positively correlates with BMI suggesting a potential role of PNX in controlling fat accumulation in obesity. Since the influence of PNX on adipose tissue formation has not been so far demonstrated, we investigated the effects of PNX on proliferation and differentiation of preadipocytes using 3T3-L1 and rat primary preadipocytes. We detected Smim20 and Gpr173 mRNA in 3T3-L1 preadipocytes as well as in rat primary preadipocytes. Furthermore, we found that PNX peptide is produced and secreted from 3T3-L1 and rat primary adipocytes. PNX increased 3T3-L1 preadipocytes proliferation and viability. PNX stimulated the expression of adipogenic genes (Pparγ, C/ebpβ and Fabp4) in 3T3-L1 adipocytes. 3T3-L1 preadipocytes differentiated in the presence of PNX had increased lipid content. Stimulation of cell proliferation and differentiation by PNX was also confirmed in rat preadipocytes. PNX failed to induce AKT phosphorylation, however, PNX increased cAMP levels in 3T3-L1 cells. Suppression of Epac signalling attenuated PNX-induced Pparγ expression without affecting cell proliferation. Our data show that PNX stimulates differentiation of 3T3-L1 and rat primary preadipocytes into mature adipocytes via cAMP/Epac-dependent pathway. In conclusion our data shows that phoenixin promotes white adipogenesis, thereby may be involved in controlling body mass regulation.     

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well‐known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue‐resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix‐modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue‐resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high‐fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age‐related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age‐related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.     

Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis

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Metabolic reprogramming in colon cancer reversed by DHTS through regulating PTEN/AKT/HIF1α mediated signal pathway

Background

Metabolic reprogramming and hypoxia contribute to the resistance of conventional chemotherapeutic drugs in kinds of cancers. In this study, we investigated the effect of dihydrotanshinone I (DHTS) on reversing dysregulated metabolism of glucose and fatty acid in colon cancer and elucidated its mechanism of action.

Paradigm shift – Metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery

Fatty acid drug discovery (FADD) is defined as the identification of novel, specialized bioactive mediators that are derived from fatty acids and have precise pharmacological/therapeutic potential. A number of reports indicate that dietary intake of omega-3 fatty acids and limited intake of omega-6 promotes overall health benefits. In 1929, Burr and Burr indicated the significant role of essential fatty acids for survival and functional health of many organs. In reference to specific dietary benefits of differential omega-3 fatty acids, docosahexaenoic and eicosapentaenoic acids (DHA and EPA) are transformed to monohydroxy, dihydroxy, trihydroxy, and other complex mediators during infection, injury, and exercise to resolve inflammation. The presented FADD approach describes the metabolic transformation of DHA and EPA in response to injury, infection, and exercise to govern uncontrolled inflammation. Metabolic transformation of DHA and EPA into a number of pro-resolving molecules exemplifies a novel, inexpensive approach compared to traditional, expensive drug discovery. DHA and EPA have been recommended for prevention of cardiovascular disease since 1970. Therefore, the FADD approach is relevant to cardiovascular disease and resolution of inflammation in many injury models. Future research demands identification of novel action targets, receptors for biomolecules, mechanism(s), and drug-interactions with resolvins in order to maintain homeostasis.     

Seed Polyphenolic Profile,Antioxidative Activity,and Fatty Acids Composition of Wild and Cultivated Carthamus Species

Total flavonoid content (TFC) and cyanidin‐3‐glucoside (Cyd‐3‐glu) of seed and seed coat extract of 16 genotypes from five species of Carthamus were studied, and their major polyphenolic compounds and antioxidant activity of the seed coat extracts were determined using HPLC analysis and DPPH assay, respectively. Additionally, fatty acids composition of the seed oil was analyzed by GC. In general, TFC and Cyd‐3‐glu content of seed coat extracts were higher than those of seed extracts. A novel breeding line with black seed coat (named A82) depicted lower TFC (3.79 mg QUE/g DW) but higher Cyd‐3‐glu (24.64 mg/g DW) compared to the white and other seed‐pigmented genotypes. DPPH radical scavenging activity showed a strong association with Cyd‐3‐glu content (r = 0.84), but no correlation with TFC (r = ?0.32). HPLC analysis of seed coat extracts revealed that four compounds were dominant constituents including rutin (7.23 – 117.95 mg/100 g DW), apigenin (4.37 – 64.88 mg/100 g DW), quercetin (3.09 – 14.10 mg/100 g DW), and ferulic acid (4.49 – 30.41 mg/100 g DW). Interestingly, the genotype A82 with an appropriate polyunsaturated/saturated fatty acids index (5.46%) and a moderate linoleic fatty acid content (64.70%) had higher nutritional and pharmaceutical value than all the other genotypes.     

Bioactivity‐Guided Isolation of Anti‐Inflammatory Constituents of the Rare Mushroom Calvatia nipponica in LPS‐Stimulated RAW264.7 Macrophages

Calvatia species, generally known as puffball mushrooms, are used both as sources of food and as traditional medicine. Among the Calvatia genus, Calvatia nipponica (Agaricaceae) is one of the rarest species. Using bioassay‐guided fractionation based on anti‐inflammatory effects, five alkaloids ( 1 – 5 ), two phenolics ( 6 and 7 ), and a fatty acid methyl ester ( 8 ) were isolated from the fruiting bodies of C. nipponica. Compound 8 was identified from C. nipponica for the first time, and all isolates ( 1 – 8 ) were tested for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophages. Compound 7 showed mild inhibition while compound 8 significantly inhibited NO production with an IC₅₀ value of 27.50 ± 0.08 μm . The mechanism of NO inhibition of compound 7 was simulated by molecular docking analysis against nitric oxide synthase (iNOS), which revealed the interactions of 7 with the key amino acid residue and the heme in the active site. With the most potent inhibition against LPS‐induced inflammation, compound 8 was further investigated with respect to its mechanism of action, and the activity was found to be mediated through the inhibition of iNOS and COX‐2 expression.     

Effect of cellobiose supplementation and dietary soluble fibre content on in vitro caecal fermentation of carbohydrate-rich substrates in rabbits

The in vitro caecal fermentation of five substrates low in starch and protein content [d-(+)-glucose (GLU), d-cellobiose (CEL), sugar beet pectin (PEC), sugar beet pulp (SBP) and wheat straw (WS)] was investigated using soft faeces from rabbits receiving different levels of cellobiose and soluble fibre as inoculum. A total of 24 rabbits were supplemented 3 levels of cellobiose in the drinking water (0.0, 7.5, 15.0 g/l) and fed two experimental diets containing either low soluble fibre (LSF) or high soluble fibre (HSF) levels (84.0 and 130 g/kg dry matter). All substrates were subjected to a two-step pepsin/pancreatin in vitro pre-digestion, and the whole residue was used as substrate for the in vitro incubations. Gas production was measured until 144 h, and volatile fatty acid (VFA) production was determined at 24 h incubation. Experimental treatments did not affect SBP fermentation and had only a subtle influence on fermentation of WS and GLU. In contrast, cellobiose supplementation × donors’ diet interactions were detected for most gas production parameters for CEL. Both the fractional gas production (k) and maximal gas production rates were linearly increased (p ≤ 0.042) and the initial delay in the onset of gas production (Lag) linearly decreased (p < 0.001) by cellobiose supplementation with the HSF inoculum, with no differences between the 7.5 and 15.0 doses. In contrast, with the LSF inoculum cellobiose supplementation only affected k values, which were quadratically increased (p = 0.043) and had maximal values for the 7.5 dose. A quadratic effect (p ≤ 0.018) of cellobiose supplementation was observed for total VFA production at 24 h when CEL and PEC were fermented, obtaining the maximal VFA production for the 7.5 dose of cellobiose. Total VFA production for CEL was greater with LSF than with HSF inoculum (20.7 vs. 12.9 mmol/l; p = 0.014), but the opposite was found for WS (3.97 vs. 6.21 mmol/l; p = 0.005). The use of LSF inoculum for CEL fermentation sharply reduced acetate (p = 0.001) and increased butyrate proportions (p ≤ 0.001) compared with the HSF inoculum. A positive relationship between total VFA caecal concentrations in rabbits receiving the same experimental treatments and in vitro values was only observed when WS was used as substrate (r = 0.90; p = 0.015; n = 6). The results suggest that experimental factors influenced the fermentative activity of caecal digesta, but the observed response differed with the incubated substrate, being the CEL the most affected.