Shimotoyodome A, Suzuki J, Fukuoka D, Tokimitsu I, Hase T. RS4-type resistant starch prevents high-fat diet-induced obesity via increased hepatic fatty acid oxidation and decreased postprandial GIP in C57BL/6J mice. Am J Physiol Endocrinol Metab 298: E652-E662, 2010. First published December 15, 2009 doi:10.1152/ajpendo.00468.2009.-Chemically modified starches (CMS) are RS4-type resistant starch, which shows a reduced availability, as well as high-amylose corn starch (HACS, RS2 type), compared with the corresponding unmodified starch. Previous studies have shown that RS4 increases fecal excretion of bile acids and reduces zinc and iron absorption in rats. The aim of this study was to investigate the effects of dietary RS4 supplementation on the development of diet-induced obesity in mice. Weight-and agematched male C57BL/6J mice were fed for 24 wk on a high-fat diet containing unmodified starch, hydroxypropylated distarch phosphate (RS4), or HACS (RS2). Those fed the RS4 diet had significantly lower body weight and visceral fat weight than those fed either unmodified starch or the RS2 diet. Those fed the RS4 diet for 4 wk had a significantly higher hepatic fatty acid oxidation capacity and related gene expression and lower blood insulin than those fed either unmodified starch or the RS2 diet. Indirect calorimetry showed that the RS4 group exhibited higher energy expenditure and fat utilization compared with the RS2 group. When gavaged with fat (trioleate), RS4 stimulated a lower postprandial glucose-dependent insulinotropic polypeptide (GIP; incretin) response than RS2. Higher blood GIP levels induced by chronic GIP administration reduced fat utilization in high-fat diet-fed mice. In conclusion, dietary supplementation with RS4-type resistant starch attenuates high-fat diet-induced obesity more effectively than RS2 in C57BL/6J mice, which may be attributable to lower postprandial GIP and increased fat catabolism in the liver.glucose-dependent insulinotropic polypeptide; insulin RESISTANT STARCH (RS) is defined as the sum of starch and the products of starch degradation not absorbed in the small intestine of healthy individuals (6). According to the standard method of the American Association of Cereal Chemists to determine dietary fiber (DF) levels (4), RS is an insoluble DF (48) that escapes hydrolysis in the small intestine and enters the large intestine (5). In this regard, RS possesses physiological properties similar to those of DF (10).RS is currently divided into four categories: physically inaccessible starch (RS1), resistant granules and high-amylose starches (RS2), retrograded starches (RS3), and chemically modified starches (CMS; RS4) (22). High-amylose corn starch (HACS) contains RS2, ungelatinized starch granules that are highly resistant to digestion by ␣-amylase until gelatinized. Several studies have shown that HACS (RS2) reduces serum cholesterol and triglyceride concentrations in rats (17,30,53) and hamsters (49).CMS are RS4-type resistant starch, which are more resistant to retrogradation, hav...

The precise role of fat in postprandial glycemia and insulinemia has not been thoroughly researched because postprandial blood glucose and concurrent insulin secretion are largely assumed to be proportional to carbohydrate intake. Recent studies have suggested that dietary fat differentially regulates the postprandial insulin response. To explore this, we examined the effects of coadministered fat on glucose-induced glycemia and insulinemia in C57BL/6J mice. The insulin response to glucose was augmented by the addition of glycerol trioleate (TO) in a dose-dependent manner, which was associated with enhanced glucose transport from the circulation to muscle and adipose tissues. To investigate the mechanism underlying fat-induced hyperinsulinemia, we examined the release of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1. TO increased GIP secretion, whereas glucagon-like peptide-1 secretion was unaffected. TO-induced hyperinsulinemia was significantly attenuated by the pretreatment of mice with a specific GIP antagonist. Diacylglycerol (DAG) promoted lower postprandial GIP and triglyceride responses and, when ingested with glucose, a lower insulin response compared with triacylglycerol of a similar fatty acid composition. Pluronic L-81, an inhibitor of chylomicron formation, reduced not only the triglyceride response but also TO-induced GIP secretion, indicating that the lower GIP response after DAG ingestion may be associated with retarded chylomicron formation in the small intestine. We conclude that dietary fat augments glucose-induced insulinemia via gut-derived GIP and, thereby, influences postprandial nutrient metabolism in mice. DAG promotes a lower GIP and thereby reduced insulin responses compared with triacylglycerol, which may differentially influence postprandial energy homeostasis.

Obesity is now a worldwide health problem. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone that is secreted following the ingestion of food and modulates energy metabolism. Previous studies reported that lowering diet-induced GIP secretion improved energy homeostasis in animals and humans, and attenuated diet-induced obesity in mice. Therefore, food-derived GIP regulators may be used in the development of foods that prevent obesity. Rice bran oil and its components are known to have beneficial effects on health. Therefore, the aim of the present study was to clarify the effects of the oil-soluble components of rice bran on postprandial GIP secretion and obesity in mice. Triterpene alcohols [cycloartenol (CA) and 24-methylene cycloartanol (24Me)], β-sitosterol, and campesterol decreased the diet-induced secretion of GIP in C57BL/6J mice. Mice fed a high-fat diet supplemented with a triterpene alcohol and sterol preparation (TASP) from rice bran for 23 wk gained less weight than control mice. Indirect calorimetry revealed that fat utilization was higher in TASP-fed mice than in control mice. Fatty acid oxidation-related gene expression in the muscles of mice fed a TASP-supplemented diet was enhanced, whereas fatty acid synthesis-related gene expression in the liver was suppressed. The treatment of HepG2 cells with CA and 24Me decreased the gene expression of sterol regulatory element-binding protein (SREBP)-1c. In conclusion, we clarified for the first time that triterpene alcohols and sterols from rice bran prevented diet-induced obesity by increasing fatty acid oxidation in muscles and decreasing fatty acid synthesis in the liver through GIP-dependent and GIP-independent mechanisms.

-Postprandial secretion of insulin and glucose-dependent insulinotropic polypeptide (GIP) is differentially regulated by not only dietary carbohydrate but also fat. Recent studies have shown that the ingestion of diacylglycerol (DAG) results in lower postprandial insulin and GIP release than that of triacylglycerol (TAG), suggesting a possible mechanism for the antiobesity effect of DAG. The structural and metabolic characteristics of DAG are believed to be responsible for its beneficial effects. This study was designed to clarify the effect of 1-monoacylglycerol [oleic acid-rich (1-MO)], the characteristic metabolite of DAG, on postprandial insulin and GIP secretion, and the underlying mechanism. Dietary 1-MO dose dependently stimulated whole body fat utilization, and reduced high-fat diet-induced body weight gain and visceral fat accumulation in mice, both of which are consistent with the physiological effect of dietary DAG. Although glucose-stimulated insulin and GIP release was augmented by the addition of fat, coingestion of 1-MO reduced the postprandial hormone release in a dose-dependent manner. Either glucose or fatty acid transport into the everted intestinal sacs and enteroendocrine HuTu-80 cells was also reduced by the addition of 1-MO. Reduction of either glucose or fatty acid transport or the nutrient-stimulated GIP release by 1-MO was nullified when the intestine was pretreated with sodium-glucose cotransporter-1 (SGLT-1) or fatty acid translocase (FAT)/CD36 inhibitor. We conclude that dietary 1-MO attenuates postprandial GIP and insulin secretion by reducing the intestinal transport of the GIP secretagogues, which may be mediated via SGLT-1 and FAT/CD36. Reduced secretion of these anabolic hormones by 1-MO may be related to the antiobesity effect of DAG.FAT/CD36; indirect calorimetry; insulin; intestinal transport; SGLT-1 THE WIDESPREAD PREVALENCE of obesity is now a worldwide health problem. Excess adiposity, especially excess abdominal fat accumulation, increases the risk of morbidity from a number of diseases, including diabetes, hypertension, and cardiovascular diseases and is also associated with a greater risk for certain cancers (25). Therefore, improvement of lifestyle, particularly dietary content, is often recommended for the primary prevention and treatment of these diseases. Diacylglycerol (DAG), which consists of 1,3-DAG and 1,2(2,3)-DAG is contained in natural edible oils at a level of 2-10% (8) and is consumed in the daily human diet. Prior studies in animals and humans have shown that dietary DAG oil composed mainly of 1,3-DAG leads to the suppression of body fat accumulation, body weight loss, improved glucose tolerance, and lower postprandial lipemia compared with that of triacylglycerol (TAG), which has a similar fatty acid composition (32, 39). Recent studies have shown that the ingestion of a 1,3-DAG-rich diet results in a lower postprandial insulin response than that of TAG oil in humans (33, 40). Since a high-level postprandial insulin response has been shown to be associate...

An RS4-type resistant starch is a chemically modified starch that shows reduced availability in comparison to the corresponding unmodified starch. Hydroxypropylated distarch phosphate (HDP) is an RS4-type resistant starch that increases energy expenditure and prevents high-fat diet-induced obesity through increased hepatic fatty acid oxidation. The aim of this study was to clarify the acute effects of HDP from tapioca starch (HPdTSP) on physical performance in mice. Male C57BL/6J mice were used to examine the effects of a single administration of 2 mg/g body weight HPdTSP or unmodified tapioca starch (TS) on postprandial responses in serum metabolic parameters, running endurance capacity on a treadmill, whole-body energy metabolism during exercise, activity of enzymes involved in fatty acid oxidation, liver and gastrocnemius muscle glycogen content, and serum glucose, insulin, non-esterified fatty acid, lactate, and triglyceride levels after exercise. Running time to fatigue was significantly greater in HPdTSP mice than in TS mice. Furthermore, HPdTSP maintained higher fat oxidation and this was associated with a greater activity of enzymes in fatty acid oxidation in the muscle during exercise. The blood lactate and serum insulin levels after exercise was significantly lower in HPdTSP mice than in TS mice. Liver glycogen was significantly higher in HPdTSP mice than in TS mice. These results suggest that acute oral administration of the RS4-type resistant starch, HPdTSP, maintained higher fat oxidation and reduced liver glycogen consumption during exercise and increased running endurance capacity in mice.