Influence de l'oligofructose sur le métabolisme glucidique et lipidique

Les fructanes sont des glucides, naturellement présents dans certains aliments, qui, de part leur structure chimique échappent à l'hydrolyse par les enzymes digestives mais sont largement fermentés dans le caeco-colon. L'oligofructose (OFS) est un fructane obtenu par hydrolyse enzymatique de l'inuline, extraite à partir de racines de chicorée. De précédentes études ont permis de démontrer un effet hypotriglycéridémiant de l'OFS, résultant d'une moindre capacité de synthèse et d'estérification des acides gras dans le foie de rats Wistar. Au cours de ce travail, nous avons progressé dans la connaissance des effets physiologiques et/ou thérapeutiques de l'OFS, en nous focalisant sur son impact sur le métabolisme glucidique et lipidique. Les études ont été réalisées sur différents modèles de rats présentants ou non des altérations du métabolisme glucidique et lipidique, mais également chez l'homme. Nous avons tenté d'élucider, chez le rat, la nature des médiateurs permettant à ces glucides non digérés d'exercer des effets systémiques. Les résultats obtenus chez le rat contrôle Wistar normoglycémique et chez le rat Zucker fa/fa insulino-résistant, présentant une hyperglycémie modérée,ne nous permettent pas de soupçonner un éventuel effet de l'OFS sur la sensibilité à l'insuline, et suggèrent que l'OFS doit être présent dans le repas pour permettre une diminution de la glycémie. Par ailleurs, chez les rats traités à la streptozotocine, hyperglycémiques et hyperphagiques, l'OFS réduit la prise alimentaire, la glycémie, et restaure partiellement la teneur en insuline pancréatique. Les concentrations en GLP-1, hormone intestinale sécrétée en réponse à l'ingestion de nutriments, sont augmentées suite à l'addition d'OFS dans le régime du rat. Le GLP-1, via son effet sur la satiété et sur la prolifération des cellules B pancréatiques pourrait constituer un médiateur des effets observés chez le rat traité à la streptozotocine. Chez le rat obèse, l'ajout de fructane dans la nourriture permet d'améliorer la stéatose hépatique, un phénomène qui serait majoritairement dépendant d'une réduction de l'apport calorique et du poids corporel engendré par le traitement. La fermentation et plus particulièrement le propionate issu de cette dernière, serait également impliqué dans cet effet anti-stéatogène de l'OFS. Une étude clinique a été réalisée en vue de tester l'influence d'une supplémentation en OFS chez des patients présentants une stéatose hépatique d'origine non alcoolique. Nous avons mis en évidence une diminution significative des taux en AST, reflet d'une moindre altération du tissu hépatique. Toutefois, aucune modification significative de la triglycéridémie, ni de la glycémie n'a pu être observée chez ces patients.Thèse de doctorat en sciences biomédicales (nutrition humaine) (SBIM 3) -- UCL, 200

Dietary fructans and lipid metabolism : building a bridge from the colon to the liver

Several non digestible but fermentable dietary carbohydrates, besides their effect on the gastrointestinal tract, are also able to exert systemic effect, namely by modifying the metabolism of lipids. The present review aims at illustrating how specific fermentable carbohydrates, namely dietary fructans, escaping the hydrolysis by amylases or disaccharidases, highly fermented in the caeco-colon by gramnegative bacteria, are susceptible to influence fatty acid metabolism and lipemia in experimental animal models, but also in humans. By focusing on the effect of oligofructose or inulin, which are dietary fructans obtained from chicorey roots, we illustrate here that the hepatic metabolism of fatty acids seems to be a relevant goal of fructans. The panel of the putative mediators of the systemic effects of fructans are presented and discussed, and consist in either 1) modifications in glucose/insulin homeostasis 2) the end-products of colonic fermentation of fructans, reaching the liver by the portal vein and /or 3) intestinal hormones and /or 4) other nutrients availability

Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese zucker rats

We studied the influence of oligofructose (OFS), a nondigestible fructan, on lipid metabolism in obese fa/fa Zucker rats. The addition of 10 g/100 g OFS to the diet slowed the increase in body weight without modifying serum triglycerides or glucose concentrations after 7 wk of treatment. However, an oral load of 2 g glucose and 5 g corn oil/kg body weight increased triglyceridemia more in OFS-fed rats than in control rats. After 10 wk, OFS decreased the hepatic concentration of triglycerides 57% relative to controls. The less severe steatosis was confirmed by histologic analysis. Among the key enzymes involved in fatty acid synthesis and esterification, only malic enzyme activity was significantly lower in OFS-fed rats than in controls. The epididymal fat mass was significantly lower in OFS-fed rats. In conclusion, dietary enrichment with OFS can counteract both the fat mass development and the hepatic steatosis that occur in obese Zucker rats. Future studies will be designed to clarify in obese animals the influence of dietary OFS on postprandial triglyceridemia, which is an important variable associated with the development of atherosclerosis in humans, and to analyze the biochemical mechanism underlying the "hepatoprotective" effect of OFS

Impact of inulin and oligofructose on gastrointestinal peptides

In the present paper, we summarise the data supporting the following hypothesis: dietary inulin-type fructans extracted from chicory root may modulate the production of peptides, such as incretins, by endocrine cells present in the intestinal mucosa, this phenomenon being involved in the regulation of food intake and/or systemic effects. To test this hypothesis, male Wistar rats received for 3 weeks either a standard diet or the same diet supplemented with 10 % inulin-type fructans with different degrees of polymerisation. All the effects were most pronounced with the diet containing oligofructose, and consisted of (i) a decrease in mean daily energy intake and in epididymal fat mass; (ii) a higher caecal pool of the anorexigenic glucagon-like peptide-1 (7-36) amide (GLP-1), and peptide YY (PYY), due to caecal tissue proliferation; (iii) an increase in GLP-1 and of its precursor - proglucagon mRNA - concentrations in the proximal colon; (iv) an increase in portal serum level of GLP-1 and PYY; (v) a decrease in serum orexigenic peptide ghrelin. Moreover, oligofructose supplementation improved glucose homeostasis (i.e. decreased glycaemia, increased pancreatic and serum insulin content) in diabetic rats previously treated with streptozotocin, a phenomenon that is partly linked to the reduction in food intake and that correlates with the increase in colic and portal GLP-1 content. Based on these results it appears justified to test, in human subjects, the hypothesis that dietary inulin-type fructans could play a role in the management of obesity and diabetes through their capacity to promote secretion of endogenous gastrointestinal peptides involved in appetite regulation

Inulin and oligofructose modulate lipid metabolism in animals : review of biochemical events and future prospects

Inulin and oligofructose, besides their effect on the gastro-intestinal tract, are also able to exert 'systemic' effect, namely by modifying the hepatic metabolism of lipids in several animal models. Feeding male Wistar rats on a carbohydrate-rich diet containing 10 % inulin or oligofructose significantly lowers serum triacylglycerol (TAG) and phospholipid concentrations. A lower hepatic lipogenesis, through a coordinate reduction of the activity and mRNA of lipogenic enzymes is a key event in the reduction of very low-density lipoprotein-TAG secretion by oligofructose. Oligofructose is also able to counteract triglyceride metabolism disorder occurring through dietary manipulation in animals, and sometimes independently on lipogenesis modulation: oligofructose reduces post-prandial triglyceridemia by 50 % and avoids the increase in serum free cholesterol level occurring in rats fed a Western-type high fat diet. Oligofructose protects rats against liver TAG accumulation (steatosis) induced by fructose, or occurring in obese Zucker fa/fa rats. The protective effect of dietary inulin and oligofructose on steatosis in animals, would be interesting, if confirmed in humans, since steatosis is one of the most frequent liver disorders, occurring together with the plurimetabolic syndrome, in overweight people. The panel of putative mediators of the systemic effects of inulin and oligofructose consists in either modifications in glucose/insulin homeostasis, the end-products of their colonic fermentation (i.e. propionate) reaching the liver by the portal vein, incretins and/or the availability of other nutrients. The identification of the key mediators of the systemic effects of inulin and oligofructose is the key to identify target function(s) (or dysfunction(s)), and finally individuals who would take an advantage of increasing their dietary intake

Involvement of endogenous glucagon-like peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats.

We have evaluated the influence of oligofructose (OFS), a fermentable dietary fibre, on glucose homeostasis, insulin production and intestinal glucagon-like peptide-1 (GLP-1) in streptozotocin-treated diabetic rats. Male Wistar rats received either i.v. streptozotocin (STZ; 40 mg/kg) or vehicle (CT); one week later, they were fed for 6 weeks with either the standard diet (STZ-CT), or with a diet containing 10% oligofructose (STZ-OFS); both diets were available ad libitum. In a second set of experiments (duration 4 weeks), a supplemental group of food-restricted rats (STZ-Res) receiving a similar intake as CT rats, was added. OFS improved glucose tolerance and reduced food intake as compared with STZ-CT rats in both the post-prandial state and after an oral glucose tolerance test. After 6 weeks, portal and pancreatic insulin concentrations were doubled in STZ-OFS rats. Food restriction improved these parameters when compared with STZ-CT rats, but to a lesser extent than in the STZ-OFS group. We have shown that OFS treatment increased portal and colonic GLP-1(7-36) amide levels and doubled colonic proglucagon and prohormone convertase 1 mRNA levels; both OFS and food restriction lowered ileal GLP-1(7-36) amide levels as compared with levels in STZ-CT rats. We propose that OFS, through its fermentation in the colon, promotes the expression and secretion of colonic peptides, namely GLP-1(7-36) amide, with beneficial consequences on glycaemia, insulin secretion and hyperphagia in diabetic rats

Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats

This study was designed to compare the effects of dietary supplementation with nondigestible carbohydrates, differing in fermentability by colonic bacteria, on hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were divided into three groups: a control group that received the basal diet, a fructan group that received 10 g highly fermented Synergy 1/100 g diet and a cellulose group that received 10 g poorly fermented Vivapur Microcrystalline cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower body weight and less triacylglycerol accumulation in the liver as assessed in vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical and histochemical analysis compared with the control and/or cellulose groups. The high fermentation of fructans compared with cellulose was reflected by greater cecal contents and by a twofold greater propionate concentration in the portal vein of rats fed fructan compared with those fed cellulose. By measuring the capacity of hepatocytes isolated from liver of Zucker rats to synthesize triglycerides or total lipids from different precursors, we showed that propionate, at the concentrations measured in the portal vein of rats treated with fructan, selectively decreased the incorporation of acetate into total lipids, a phenomenon that could contribute, along with the lower energy intake, to less triglyceride accumulation in the liver of obese Zucker rats fed dietary fructans

Study of the regulation by nutrients of the expression of genes involved in lipogenesis and obesity in humans and animals.

Dietary digestible carbohydrates are able to modulate lipogenesis, by modifying the expression of genes coding for key lipogenic enzymes, like fatty acid synthase. The overall objective of the Nutrigene project (FAIR-CT97-3011) was to study the efficiency of various carbohydrates to modulate the lipogenic capacity and relevant gene expression in rat and human species (control and obese subjects) and to understand the underlying molecular mechanisms involved in the regulation of lipogenic genes by carbohydrates. Key cellular mediators (namely SREBP-1c and 2, AMP activated protein kinase, cholesterol content) of the regulation of lipogenic gene expression by glucose and/or insulin were identified and constitute new putative targets in the development of plurimetabolic syndrome associated with obesity. In humans, hepatic lipogenesis and triglyceride synthesis, assessed in vivo by the use of stable isotopes, was promoted by a high-carbohydrate diet in non obese subjects, and in non alcoholic steatotic patients, but was not modified in the adipose tissue of obese subjects. Non digestible/fermentable carbohydrates, such as fructans, were shown to decrease hepatic lipogenesis in non obese rats, and to lessen hepatic steatosis and body weight in obese Zucker rats. If confirmed in obese humans, this would allow the development of functional food able to counteract the metabolic disturbances linked to obesity