Daily Intake of Smallanthus sonchifolius (Yacon) Roots Reduces the Progression of Non-alcoholic Fatty Liver in Rats Fed a High Fructose Diet.

High-fructose diet is associated with an increased risk of dyslipidemia, metabolic syndrome, and the development of non-alcoholic fatty liver disease (NAFLD) through chronic inflammation. The present study aimed to elucidate the potential benefit of daily consumption of Smallanthus sonchifolius (yacon) roots, rich in fructooligosaccharides (FOS), on the progression to liver fibrosis, in a rat model of NAFLD induced by a high-fructose diet. Male Wistar rats were fed a standard diet (CD, n = 6) or a standard diet plus 10% fructose solution (FD; n = 18). After 20 weeks, FD rats were randomly separated into the following groups (n = 6, each): FD; FD treated with yacon flour (340 mg FOS/body weight; FD + Y) and FD treated with fenofibrate (30 mg/kg body weight; FD + F), for 16 weeks. Daily intake of yacon flour significantly reduced body weight gain, plasma lipid levels, transaminase activities, and improved systemic insulin response in FD rats. In the liver, yacon treatment decreased fructose-induced steatosis and inflammation, and reduced total collagen deposition (64%). Also, yacon decreased TGF-ß1 mRNA expression (78%), followed by decreased nuclear localization of p-Smad2/3 in liver tissue. Yacon significantly reduced the expression of α-smooth muscle actin (α-SMA), Col1α1, and Col3α1 mRNAs (85, 44, and 47%, respectively), inhibiting the activation of resident hepatic stellate cells (HSCs). These results suggested that yacon roots have the potential to ameliorate liver damage caused by long-term consumption of a high-fructose diet, being a promising nutritional strategy in NAFLD management.

Smallanthus sonchifolius (Yacon) Flour Improves Visceral Adiposity and Metabolic Parameters in High-Fat-Diet-Fed Rats.

Smallanthus sonchifolius (yacon), a native plant of South America, was observed to improve lipid profile in rodents and humans. This study aimed to investigate the antiobesity properties of yacon roots in a high-fat-diet (HFD) model and the underlying mechanisms. A total of 30 Wistar male rats were divided into five groups (n=6): the standard chow diet (SD) group was fed a SD; the HFD group was fed a HFD; and the HFD Y340 and HFD Y680 groups were fed a HFD plus yacon flour (340 and 680 mg FOS/kg b. w./day, respectively). HFD Y340 and HFD Y680 rats exhibited marked attenuation of weight gain, a decrease in visceral fat pad weight, a restoration of the serum lipid profile and atherogenic index in a dose-dependent manner, being the higher dose more effective (p < 0.05). In addition, we found that HFD Y680 rats showed lower glucose and insulin levels, improved glucose tolerance, and insulin sensitivity (p < 0.5). A downregulation of several adipocyte specific-transcription factors, including peroxisome proliferator-activated receptor gamma2 (PPAR-γ2), CCAAT/enhancer binding protein a (C/EBP-a) and activating protein (aP2) mRNA levels, was determined in the visceral adipose tissue of HFD Y680 rats (p < 0.05). An improvement of adipokine profile in HFD Y680 rats and decreased serum proinflammatory cytokine levels (p < 0.05) were determined by ELISA. Decreased macrophage infiltration and F4/80 and MCP-1 expression in the visceral adipose tissue of HFD Y680 rats (p < 0.5), together with a higher pAkt/Akt expression (p < 0.05) were also observed by immunofluorescence and immunoblotting. A significant increase in glucagon (Gcg) and PYY mRNA levels in distal ileum of HFD Y680 rats (p < 0.05) were also detected. In the second approach, we determined that yacon supplementation potentiates the effects of the HFD reversion to a standard diet. In conclusion, yacon showed antiobesity properties by inhibiting adipogenesis and improving the visceral adipose tissue function.

Paraxis is required for somite morphogenesis and differentiation in Xenopus laevis.

BACKGROUND: In most vertebrates, the segmentation of the paraxial mesoderm involves the formation of metameric units called somites through a mesenchymal-epithelial transition. However, this process is different in Xenopus laevis because it does not form an epithelial somite. Xenopus somitogenesis is characterized by a complex cells rearrangement that requires the coordinated regulation of cell shape, adhesion, and motility. The molecular mechanisms that control these cell behaviors underlying somite formation are little known. Although the Paraxis has been implicated in the epithelialization of somite in chick and mouse, its role in Xenopus somite morphogenesis has not been determined. RESULTS: Using a morpholino and hormone-inducible construction approaches, we showed that both gain and loss of function of paraxis affect somite elongation, rotation and alignment, causing a severe disorganization of somitic tissue. We further found that depletion or overexpression of paraxis in the somite led to the downregulation or upregulation, respectively, of cell adhesion expression markers. Finally, we demonstrated that paraxis is necessary for the proper expression of myotomal and sclerotomal differentiation markers. CONCLUSIONS: Our results demonstrate that paraxis regulates the cell rearrangements that take place during the somitogenesis of Xenopus by regulating cell adhesion. Furthermore, paraxis is also required for somite differentiation.

Xepac protein and IP3/Ca2+ pathway implication during Xenopus laevis vitellogenesis.

The objective of this study was to elucidate the signalling pathways initiated by cAMP once inside the Xenopus laevis oocyte, where it triggers and maintains vitellogenin endocytic uptake. Our results showed the presence of Xepac transcripts at all stages of oogenesis and we demonstrated that a cAMP analogue that exclusively activates Xepac, 8-CPT, was able to rescue the endocytic activity in oocytes with uncoupled gap junctions. Inhibition experiments for the IP3/Ca2+ signalling pathway showed either a complete inhibition or a significant reduction of the vitellogenic process. These results were confirmed with the rescue capability of the A-23187 ionophore in those oocyte batches in which the IP3/Ca2+ pathway was inhibited. Taking our findings into account, we propose that the cAMP molecule binds Xepac protein enabling it to activate the IP3/Ca2+ pathway, which is necessary to start and maintain X. laevis vitellogenin uptake.

Involvement of cAMP and calmodulin in endocytic yolk uptake during Xenopus laevis oogenesis.

The aim of the present study was to show the participation and physiological role of calmodulin (CaM) and cAMP during vitellogenin endocytic uptake in the amphibian Xenopus laevis. The results showed a differential distribution of CaM in the ovary follicles during oogenesis. The CaM intracellular localization was not affected by gap junction's downregulation and CaM inhibition did not completely abolished the endocytic activity of oocytes. We showed that cAMP was able to completely rescue the endocytic competence in follicles in which gap junctional communication had been disrupted by octanol. Moreover cAMP was capable of restoring oocyte endocytic capability in the presence of octanol and stelazine, a CaM inhibitor. We propose that, in Vtg uptake regulation, cAMP is upstream of CaM during the endocytic signalling pathway.

Safety assessment of aqueous extract from leaf Smallanthus sonchifolius and its main active lactone, enhydrin.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson (yacon) have been used since pre-Columbian times in the Andean region to prepare medicinal herbal tea with beneficial health properties. However, there are still disagreements about the safe use. This work was carried out to evaluate the toxicity profile of both, 10% decoction of yacon leaves and their major active lactone, enhydrin. MATERIALS AND METHODS: In vitro cytotoxicity assays were performed with Hep-G2, COS1, CHO-K1 and Vero cell lines using a test of metabolic competence based upon assessment of mitochondrial performance. In vivo toxicity study was performed in adult Wistar rats. In the acute oral toxicity each group of rats was orally given a single dose of 10% decoction or enhydrin. General condition, behavior and mortality were recorded for up to 14 days post treatment. In subchronic toxicity studies, both products were given orally for 90 days to rats. Body weight and food intakes were observed weekly. Hematological, clinical chemistry parameters and organ weight were determined in all animals at the end of the experimental period. RESULTS: Cell viability decreased in a concentration dependent fashion when cells were incubated with 2-200 µg of 10% decoction and 0.015-7.5 µg of enhydrin. In acute study in rats, there were no deaths or signs of toxicity observed after oral administration of single doses of 10% decoction or enhydrin at any dose level up to the highest dose tested (14.0 g/kg and 0.32 g/kg, respectively). In subchronic studies in rats, both products administered orally for 90 days at daily doses of 0.07, 0.14 and 0.28 g 10% decoction/kg and 0.4, 0.8 and 8.0 mg enhydrin/kg, did not caused haematological, biochemical and histological alterations. CONCLUSIONS: The results presented in this paper lead us to the conclusion that the use of 10% decoction and enhydrin is safe in rat at doses in which it is demonstrated the hypoglycaemic effect.

Evaluación de disfunción endotelial en pacientes con diabetes tipo 2 / Dysfunction endothelial evaluation in type 2 diabetes patients

El objetivo de este trabajo fue estudiar moléculas involucradas en la activación endotelial, tales como la molécula de adhesión sE-Selectina (sE-S) y el péptido vasoconstrictor Endotelina-1 (ET-1) en individuos diabéticos tipo 2 y su asociación con otros factores de riesgo cardiovascular. Se estudiaron 62 pacientes diabéticos que se compararon con un grupo control. Las concentraciones de sE-S y ET-1 fueron significativamente mayores en los diabéticos que en los controles (sE-S: 90,6±26,2 ng/mL vs. 49,5±9,2 ng/mL, p<0,00001; ET-1: 11,3±3,7 vs. 7,7±0,5 pg/mL, p<0,001, respectivamente). Estas moléculas, en pacientes con índice de masa corporal (IMC) normal y aumentado, mostraron diferencias significativas (sE-S: 75,5±22,4 vs. 97,1±32,9 ng/mL, p<0,05; ET-1: 8,4±2,4 vs. 14,1±4,9 pg/mL, p=0,001, respectivamente). No se encontraron diferencias entre individuos diabéticos normo e hipertensos, no fumadores y fumadores, ni normo e hipercolesterolémicos. El 81% de la población estudiada presentó un pobre control glucémico (HA1c>7%), siendo significativamente mayores los niveles de ET-1 en este grupo (p<0,01) no así para sE-S (p=0,74). Los resultados obtenidos muestran que los pacientes diabéticos presentan activación endotelial reflejada en los niveles elevados de sE-S y ET-1. El IMC aumentado y el pobre control glucémico incrementan la disfunción endotelial en estos pacientes.

The object of this work was to study molecules involved in endothelial activation, such as E-selectin (sE-S) and the vasoconstrictor peptide Endothelin-1 (ET-1) in Type 2 diabetes patients, and their relation with other cardiovascular risk factors. Sixty-two patients with diabetes were compared with matched controls. sE-S and ET-1 concentrations in diabetes patients were significantly elevated compared with controls (sE-S: 90.6±26.2 ng/mL vs 49.5±9.2 ng/mL, p<0.00001; ET-1: 11.3±3.7 vs 7.7±0.5 pg/mL, p<0.001, respectively). sE-S and ET-1 levels in diabetes patients with normal and increased body mass index showed significant differences (sE-S: 75.5±22.4 vs. 97.1±32.9 ng/mL, p<0.05; ET-1: 8.4±2.4 vs. 14.1±4.9 pg/mL, p=0.001 respectively). There were no significant differences in none of the molecules values between patients with or without hypertension, smokers or non-smokers, neither in diabetes patients with or without hypercholesterolemia. Eighty-one percent of the population with diabetes presented a poor glycemic control (HA1c>7%) and in these patients, ET-1 plasma levels were significantly increased (p<0.01), but not sE-S (p=0.74). These results show that obesity and a poor glycemic control increase the endothelial dysfunction in type 2 diabetes patients.