Inulin Effects On The High-fat-diet Induced Obesity——a Metabonomics Study

Obesity is now becoming an epidemic affecting billions of people’s health and well being in both the developed and developing countries. It is well-known that genetic and environmental factors are both involved in occurrence and development of obesity. High-fat-diet (HFD) induced obesity, which is similar with most human beings’adiposis, has been one of the most widely used models to better study obesity. Numerous studies have shown obvious changes of expression of genes involved in multiple metabolic pathways, implying great association between metabonomic alterations and pathogenesis of obesity.In consideration of the high morbidity and mortality caused by obesity and its complications, researches on treatment are also growing vigorously. Less people would choose operative therapy for possible risk and injury, though with ideal weight-reducing effect. While diet intervention with little side effect is always welcome, which may fulfill both prevention and treatment of obesity as well as associated diseases. Inulin, as one kind of fructan-type prebiotics, has revealed remarkable potential on obesity resistance.However, so far, limited work was focused on HFD-induced metabolic alterations and there is also little study involved in diet intervention with inulin. Given the above, NMR-based metabonomics research approach was applied to study the inulin effects on HFD-induced obesity.Firstly, we developed a useful high-throughput method based on multiple univariate data analysis (MUDA) to visualize and efficiently extract information on metabolites significantly affected by an intervention. The findings based on MUDA demonstrated this method to be a powerful alternative to traditionally used multivariate data analysis for metabonomics.Secondly, we built a model on the HFD-induced rat obesity and inulin intervention, and analysed dynamic metabolic changes in rat plasma, urine and feces as well as metabolic alterations in multiple organs (i.e. liver, kidney, heart, pancreas, skeletal muscle, testicle, brain and eyeball), intestines and intestinal contents.7-week HFD feeding did increase body weight gain and both perirenal and epididymal fat accumulation, though without significant differences, implying animals were at the preobesity stage. The findings also showed systematically upregulated levels of fatty acid P-oxidation and ketogenesis, inflammation resulting from adipose tissue accumulation and intestinal permeability dysfunction, and inflammation accompanied oxidative stress even before HFD induced significant body-weight increase. In addition, the HFD led to specific injury to multiple organs respectively as well. Inulin intakes not only markedly prevented body-weight-gain and fat accumulation, but mitigated or prevented most adverse effects caused by the HFD. It was thought the findings that inulin decreased food and energy intakes of rats, reduced intestinal absorption rate of carbohydrates, and promoted short chain fatty acids production by enteric bacteria in the colonic lumen were in connection with the inulin obesity-resisting effects. Besides, several rare metabolic changes were observed with inulin intervention, including significant level elevation of4-methyl-2-olefinates in small intestine, porphyrins in urine and kidney, and systematic scyllo-inositol (SI).And then thirdly, we comprehensively analyzed the systematically increased SI in rat body induced by inulin-intake. It was believed that inulin had promoted the growth of some bacteria in the colon who could produce SI utilizing the dietary inulin. And the sharp level elevations of SI in rat kidney, brain and eyeball revealed the SI de novo synthesis might be upregulated.Finally, preliminary identification and exploration was performed on the porphyrins in rat urine and kidney. Through NMR and HPLC-MS data, we could nearly affirm the unknown compounds to be porphyrins. In combination with the probable increases of stercobilin and glucuronate1-phosphate, inulin-intake might directly or indirectly influnce the porphyrin metabolism. Being a primary exploration, this work warrants further study, while the existing results have proved the integration of multiple detecting techniques to be efficient and indispensable in metabonomics researches.In summary, a metabonomics study was performed on inulin effects on the HFD-induced obesity. We established a new MUDA method for metabonomic data analysis, elucidated the possible mechanisms involved in the HFD inducing adverse metabolic alterations and in the inulin obesity-resisting effects, then carried out detailed analysis on systematically increased scyllo-inositol due to inulin-intake, and finally made preliminary identification and exploration on the porphyrins in rat urine and kidney. In addition to clarifying the law of development of obesity, this work also provided new ideas on prevention and treatment for obesity and its complications.