BackgroundMetabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent models employ high fat, high cholesterol, high fructose, methionine/choline deficient diets or combinations of these to induce NAFLD/NASH. The FATZO mice spontaneously develop the above metabolic disorders and type 2 diabetes (T2D) when fed with a normal chow diet. The aim of the present study was to determine if FATZO mice fed a high fat and fructose diet would exacerbate the progression of NAFLD/NASH.MethodsMale FATZO mice at the age of 8 weeks were fed with high fat Western diet (D12079B) supplemented with 5% fructose in the drinking water (WDF) for the duration of 20 weeks. The body weight, whole body fat content, serum lipid profiles and liver function markers were examined monthly along with the assessment of liver histology for the development of NASH. In addition, the effects of obeticholic acid (OCA, 30 mg/kg, QD) on improvement of NASH progression in the model were evaluated.ResultsCompared to normal control diet (CD), FATZO mice fed with WDF were heavier with higher body fat measured by qNMR, hypercholesterolemia and had progressive elevations in AST (~ 6 fold), ALT (~ 6 fold), liver over body weight (~ 2 fold) and liver triglyceride (TG) content (1.4–2.9 fold). Histological examination displayed evidence of NAFLD/NASH, including hepatic steatosis, lobular inflammation, ballooning and fibrosis in FATZO mice fed WDF. Treatment with OCA for 15 weeks in FATZO mice on WDF significantly alleviated hypercholesterolemia and elevation of AST/ALT, reduced liver weight and liver TG contents, attenuated hepatic ballooning, but did not affect body weight and blood TG levels.ConclusionWDF fed FATZO mice represent a new model for the study of progressive NAFLD/NASH with concurrent metabolic dysregulation.
The evolution of increased competitive ability (EICA) hypothesis states that, when introduced in a novel habitat, invasive species may reallocate resources from costly quantitative defense mechanisms against enemies to dispersal and reproduction; meanwhile, the refinement of EICA suggests that concentrations of toxins used for qualitative defense against generalist herbivores may increase. Previous studies considered that only few genotypes were introduced to the new range, whereas most studies to test the EICA (or the refinement of EICA) hypotheses did not consider founder effects.
In this study, genetic and phenotypic data of Chromolaena odorata populations sampled across native and introduced ranges were combined to investigate the role of postintroduction evolution in the successful invasion of C. odorata.
Compared with native populations, the introduced populations exhibited lower levels of genetic diversity. Moreover, different founder effects events were interpreted as the main cause of the genetic structure observed in introduced ranges. Three Florida, two Trinidad, and two Puerto Rico populations may have been the sources of the invasive C. odorata in Asia.
When in free of competition conditions, C. odorata plants from introduced ranges perform better than those from native ranges at high nutrient supply but not at low nutrient level. The differences in performance due to competition were significantly greater for C. odorata plants from the native range than those from the introduced range at both nutrient levels. Moreover, the differences in performance by competition were significantly greater for putative source populations than for invasive populations.
Quantities of three types of secondary compounds in leaves of invasive C. odorata populations were significantly higher than those in putative source populations. These results provide more accurate evidence that the competitive ability of the introduced C. odorata is increased with postintroduction evolution.
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