Kathleen L McCutcheon

Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents.

Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are anti-diabetes/obesity hormones secreted from the gut after meal ingestion. We have shown that dietary-resistant starch (RS) increased GLP-1 and PYY secretion, but the mechanism remains unknown. RS is a fermentable fiber that lowers the glycemic index of the diet and liberates short-chain fatty acids (SCFAs) through fermentation in the gut. This study investigates the two possible mechanisms by which RS stimulates GLP-1 and PYY secretion: the effect of a meal or glycemic index, and the effect of fermentation. Because GLP-1 and PYY secretions are stimulated by nutrient availability in the gut, the timing of blood sample collections could influence the outcome when two diets with different glycemic indexes are compared. Thus we examined GLP-1 and PYY plasma levels at various time points over a 24-h period in RS-fed rats. In addition, we tested proglucagon (a precursor to GLP-1) and PYY gene expression patterns in specific areas of the gut of RS-fed rats and in an enteroendocrine cell line following exposure to SCFAs in vitro. Our findings are as follows. 1) RS stimulates GLP-1 and PYY secretion in a substantial day-long manner, independent of meal effect or changes in dietary glycemia. 2) Fermentation and the liberation of SCFAs in the lower gut are associated with increased proglucagon and PYY gene expression. 3) Glucose tolerance, an indicator of increased active forms of GLP-1 and PYY, was improved in RS-fed diabetic mice. We conclude that fermentation of RS is most likely the primary mechanism for increased endogenous secretions of total GLP-1 and PYY in rodents. Thus any factor that affects fermentation should be considered when dietary fermentable fiber is used to stimulate GLP-1 and PYY secretion.

Failure to ferment dietary resistant starch in specific mouse models of obesity results in no body fat loss

UNLABELLED Resistant starch (RS) is a fermentable fiber that decreases dietary energy density and results in fermentation in the lower gut. The current studies examined the effect of RS on body fat loss in mice. In a 12 week study (study 1), the effect of two different types of RS on body fat was compared with two control diets (0% RS) in C57Bl/6J mice: regular control diet or the control diet that had energy density equal to that of the RS diet (EC). All testing diets had 7% (w/w) dietary fat. In a 16 week study (study 2), the effect of RS on body fat was compared with EC in C57BL/6J mice and two obese mouse models (NONcNZO10/LtJ or Non/ShiLtJ). All mice were fed control (0% RS) or 30% RS diet for 6 weeks with 7% dietary fat. On the seventh week, the dietary fat was increased to 11% for half of the mice and remained the same for the rest. Body weight, body fat, energy intake, energy expenditure, and oral glucose tolerance were measured during the study. At the end of the studies, the pH of cecal contents was measured as an indicator of RS fermentation. Compared with EC, dietary RS decreased body fat and improved glucose tolerance in C57BL/6J mice but not in obese mice. For other metabolic characteristics measured, the alterations by RS diet were similar for all three types of mice. The difference in dietary fat did not interfere with these results. The pH of cecal contents in RS fed mice was decreased for C57BL/6J mice but not for obese mice, implying the impaired RS fermentation in obese mice. CONCLUSIONS (1) decreased body fat by RS is not simply due to dietary energy dilution in C57Bl/6J mice, and (2) along with their inability to ferment RS, RS fed obese mice did not lose body fat. Thus, colonic fermentation of RS might play an important role in the effect of RS on fat loss.

High-amylose resistant starch increases hormones and improves structure and function of the gastrointestinal tract: a microarray study.

Background/Aims: Type 2 resistant starch from high-amylose maize (HAM-RS2) is associated with increased fermentation, increased expression of proglucagon (gene for GLP-1) and peptide YY (PYY) genes in the large intestine, and improved health. To determine what other genes are up- or downregulated with feeding of HAM-RS2, a microarray was performed. Methods: Adult, male Sprague Dawley rats were fed one of the following three diets for a 4-week study period: cornstarch control (CC, 3.74 kcal/g), dietary energy density control (EC, 3.27 kcal/g), and 30% HAM-RS2 (RS, 3.27 kcal/g). Rat microarray with ∼27,000 genes and validation of 94 representative genes with multiple qPCR were used to determine gene expression in total RNA extracts of cecal cells from rats. The RS versus EC comparison tested effects of fermentation as energy density of the diet was controlled. Results: For the RS versus EC comparison, 86% of the genes were validated from the microarray and the expression indicates promotion of cell growth, proliferation, differentiation, and apoptosis. Gut hormones GLP-1 and PYY were increased. Conclusions: Gene expression results predict improved structure and function of the GI tract. Production of gut hormones may promote healthy functions beyond the GI tract.

Dietary whey protein decreases food intake and body fat in rats

We investigated the effects of dietary whey protein on food intake, body fat, and body weight gain in rats. Adult (11–12 week) male Sprague‐Dawley rats were divided into three dietary treatment groups for a 10‐week study: control. Whey protein (HP‐W), or high‐protein content control (HP‐S). Albumin was used as the basic protein source for all three diets. HP‐W and HP‐S diets contained an additional 24% (wt/wt) whey or isoflavone‐free soy protein, respectively. Food intake, body weight, body fat, respiratory quotient (RQ), plasma cholecystokinin (CCK), glucagon like peptide‐1 (GLP‐1), peptide YY (PYY), and leptin were measured during and/or at the end of the study. The results showed that body fat and body weight gain were lower (P < 0.05) at the end of study in rats fed HP‐W or HP‐S vs. control diet. The cumulative food intake measured over the 10‐week study period was lower in the HP‐W vs. control and HP‐S groups (P < 0.01). Further, HP‐W fed rats exhibited lower N2 free RQ values than did control and HP‐S groups (P < 0.01). Plasma concentrations of total GLP‐1 were higher in HP‐W and HP‐S vs. control group (P < 0.05), whereas plasma CCK, PYY, and leptin did not differ among the three groups. In conclusion, although dietary HP‐W and HP‐S each decrease body fat accumulation and body weight gain, the mechanism(s) involved appear to be different. HP‐S fed rats exhibit increased fat oxidation, whereas HP‐W fed rats show decreased food intake and increased fat oxidation, which may contribute to the effects of whey protein on body fat.

Resistant starch from high amylose maize (HAM‐RS2) and Dietary butyrate reduce abdominal fat by a different apparent mechanism

Obesity is a health concern. Resistant starch (RS) type 2 from high‐amylose maize (HAM‐RS2) and dietary sodium butyrate (SB) reduce abdominal fat in rodents. RS treatment is associated with increased gut hormones peptide YY (PYY) and glucagon‐like peptide 1 (GLP‐1), but it is not known if SB increases these hormones.

High fat diet partially attenuates fermentation responses in rats fed resistant starch from high-amylose maize

The effects of type 2 resistant starch from high‐amylose maize (HAM‐RS2) in rodents fed with low‐fat diets were demonstrated in previous studies. Fish oil is also reported to reduce body fat. In the current study, the effects of high fat and fish oil on HAM‐RS2 feeding in rats were investigated.

Resistant starch from high amylose maize (HAM-RS2) reduces body fat and increases gut bacteria in ovariectomized (OVX) rats†‡

Obesity after menopause is a health concern for older females. Changes in the microbiota are likely to occur with this condition. Modifying the microbiota with a prebiotic is a plausible strategy for improving the health of menopausal females.

Improvement of Obesity Phenotype by Chinese Sweet Leaf Tea (Rubus suavissimus) Components in High-Fat Diet-Induced Obese Rats

Drinking an herbal tea to lose weight is a well-liked concept. This study was designed to examine the possible improvement of obesity phenotype by a new tea represented by its purified components, gallic acid, ellagic acid, and rubusoside (GER). Male obese-prone SD rats were given low-fat diet, high-fat diet, or high-fat diet plus GER at the dose of 0.22 g/kg of body weight for 9 weeks. GER significantly reduced body weight gain by 22% compared to the high-fat diet control group with 48% less abdominal fat gain. Food intake was not affected. Blood glucose was lowered in the GER-treated group, whereas serum triglycerides and cholesterol were significantly reduced by 50%. This improved obesity phenotype may be associated with the attenuated expression of vascular endothelial growth factor in preadipocyte 3T3-L1 cells. Although other underlying, possibly multiple, mechanisms behind the improved phenotype are largely unknown, the observed improvement of multiple obesity-related parameters by the new tea warrants further investigations.

Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents

Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast.