Lindsay K. Eller

Dairy protein attenuates weight gain in obese rats better than whey or casein alone.

Evidence suggests that dietary calcium (Ca) and particularly dairy foods may attenuate weight gain and improve symptoms of the metabolic syndrome. The purpose of this study was to determine the effect of different Ca‐enriched dairy protein sources on the prevention of weight gain in Sprague‐Dawley diet‐induced obese (DIO) rats. Twelve week‐old DIO rats were assigned to one of eight ad libitum diets that varied in protein source (casein, whey, or complete dairy), Ca content (0.67 or 2.4%) and energy level (high fat/high sucrose (HFHS); or normal calorie density (NC)). Body composition and response to a meal tolerance test (MTT) were measured. Average daily caloric intake did not differ within normal or high energy density groups. At the end of 8 weeks, the dairy/HFHS/0.67% and 2.4% groups had significantly lower body weight than all other HFHS groups. The dairy/HFHS/0.67% and 2.4% groups also had lower body fat and greater lean mass expressed as a percent (P < 0.05). Homeostatic model assessment of insulin resistance (HOMAIR) was lowest for dairy/HFHS/0.67% and significantly different from whey/HFHS/0.67% and 2.4%. Independent of protein source, high Ca decreased plasma insulin at 30 min in the MTT more so than low Ca (P < 0.05). Hepatic sterol regulatory element–binding protein (SREBP1c) and peroxisome proliferator–activated receptor‐γ (PPARγ) mRNA was downregulated by dairy and whey compared to casein in the HFHS/0.67% diets. Overall, these data suggest that complete dairy improves body composition and insulin sensitivity to a greater extent than whey or casein alone.

Consumption of diets high in prebiotic fiber or protein during growth influences the response to a high fat and sucrose diet in adulthood in rats

BackgroundEarly dietary exposure can influence susceptibility to obesity and type 2 diabetes later in life. We examined the lasting effects of a high protein or high prebiotic fiber weaning diet when followed by a high energy diet in adulthood.MethodsAt birth, litters of Wistar rats were culled to 10 pups. At 21 d pups were weaned onto control (C), high prebiotic fiber (HF) or high protein (HP) diet. Rats consumed the experimental diets until 14 wk when they were switched to a high fat/sucrose (HFHS) diet for 6 wk. Body composition and energy intake were measured and an oral glucose tolerance test (OGTT) performed. Blood was analyzed for satiety hormones and tissues collected for real-time PCR.ResultsWeight gain was attenuated in male rats fed HF from 12 wk until study completion. In females there were early reductions in body weight that moderated until the final two wk of HFHS diet wherein HF females weighed less than HP. Final body weight was significantly higher following the high fat challenge in male and female rats that consumed HP diet from weaning compared to HF. Lean mass was higher and fat mass lower with HF compared to HP and compared to C in males. Energy intake was highest in HP rats, particularly at the start of HFHS feeding. Plasma glucose was higher in HP rats compared to HF during an OGTT. Plasma amylin was higher in HF females compared to C and glucagon-like peptide-1 (GLP-1) was higher in HF rats during the OGTT. Leptin was higher in HP rats during the OGTT. HF upregulated GLUT 5 mRNA expression in the intestine and downregulated hepatic hydroxymethylglutaryl coenzyme A reductase. Male rats fed HP had higher hepatic triglyceride content than C or HF.ConclusionThese data suggest that while a long-term diet high in protein predisposes to an obese phenotype when rats are given a high energy diet in adulthood, consumption of a high fiber diet during growth may provide some protection.

Satiety Hormone and Metabolomic Response to an Intermittent High Energy Diet Differs in Rats Consuming Long-Term Diets High in Protein or Prebiotic Fiber

Large differences in the composition of diet between early development and adulthood can have detrimental effects on obesity risk. We examined the effects of an intermittent high fat/sucrose diet (HFS) on satiety hormone and serum metabolite response in disparate diets. Wistar rat pups were fed control (C), high prebiotic fiber (HF) or high protein (HP) diets (weaning to 16 weeks), HFS diet challenged (6 weeks), and finally reverted to their respective C, HF, or HP diet (4 weeks). At conclusion, measurement of body composition and satiety hormones was accompanied by 1H NMR metabolic profiles in fasted and postprandial states. Metabolomic profiling predicted dietary source with >90% accuracy. The HF group was characterized by lowest body weight and body fat (P < 0.05) and increased satiety hormone levels (glucagon-like peptide 1 and peptide-YY). Regularized modeling confirmed that the HF diet is associated with higher gut hormone secretion that could reflect the known effects of prebiotics on gut microbiota and their fementative end products, the short chain fatty acids. Rats reared on a HF diet appear to experience fewer adverse effects from an intermittent high fat diet in adulthood when rematched to their postnatal diet. Metabolite profiles associated with the diets provide a distinct biochemical signature of their effects.

The neutral cannabinoid CB1 receptor antagonist AM4113 regulates body weight through changes in energy intake in the rat

The aim of this study was to determine if the neutral cannabinoid CB₁ receptor antagonist, AM4113, regulates body weight in the rat via changes in food intake. We confirmed that the AM4113-induced reduction in food intake is mediated by CB₁ receptors using CB₁ receptor knockout mice. In rats, intraperitoneally administered AM4113 (2, 10 mg kg⁻¹) had a transient inhibitory effect on food intake, while body weight gain was suppressed for the duration of the study. AM4113-induced hypophagia was no longer observed once the inhibitory effect of AM4113 on body weight stabilized, at which time rats gained weight at a similar rate to vehicle-treated animals, yet at a lower magnitude. Pair-feeding produced similar effects to treatment with AM4113. Food intake and body weight gain were also inhibited in rats by oral administration of AM4113 (50 mg kg⁻¹). Dual energy x-ray absorptiometry (DEXA) was used to measure lean and fat mass. The AM4113 treated group had 29.3±11.4% lower fat mass than vehicle-treated rats; this trend did not reach statistical significance. There were no differences in circulating levels of the endogenous cannabinoid 2-arachidonoyl glycerol (2-AG), glucose, triglycerides, or cholesterol observed between treatment groups. Similarly, 2-AG hypothalamic levels were not modified by AM4113 treatment. These data suggest that blockade of an endocannabinoid tone acting at CB₁ receptors induces an initial, transient reduction in food intake which results in long-term reduction of body weight gain.

A High Calcium, Skim Milk Powder Diet Results in a Lower Fat Mass in Male, Energy-Restricted, Obese Rats More Than a Low Calcium, Casein, or Soy Protein Diet

The combination of dairy protein and dietary calcium (Ca) may enhance weight loss more effectively than either compound alone. Our purpose in this study was to determine the effect of various protein sources [skim milk powder (SMP), whey, casein, and soy protein isolate (SPI)] and 2 levels of Ca [low, 0.67% Ca (LC) or high, 2.4% Ca (HC)] on weight loss. Sixty-four 12-wk-old Sprague-Dawley, diet-induced obese rats were assigned to 1 of 8 energy-restricted (ER) diets for 4 wk with 1 of the 4 protein sources and either LC or HC concentrations. Rats were ER to 70% of the ad libitum food and energy intake of a reference group (n = 8) fed the AIN-93M diet. The interaction between dietary protein and Ca affected final body weight and fat mass (FM) (P < 0.05). FM was less in rats fed SMP-HC than in those fed casein-LC or SPI-LC. Lean body mass was greater in rats fed SMP than in those fed whey. Rats fed HC diets had a lower plasma glucagon area under the curve (AUC) than those fed LC diets. The blood glucose AUC, homeostatic model of insulin resistance, and the expression of certain hepatic genes involved in energy metabolism were affected by protein and Ca. These data suggest that consuming a diet containing SMP and HC is associated with a lower FM in obese, male, ER rats than in diets containing casein or SPI and LC; however, the role of SMP and Ca in glucose homeostasis remains to be determined.

Interactive effects of oligofructose and obesity predisposition on gut hormones and microbiota in diet-induced obese rats

Oligofructose (OFS) is a prebiotic that reduces energy intake and fat mass via changes in gut satiety hormones and microbiota. The effects of OFS may vary depending on predisposition to obesity. The aim of this study was to examine the effect of OFS in diet‐induced obese (DIO) and diet‐resistant (DR) rats.

Dietary leucine improves whole-body insulin sensitivity independent of body fat in diet-induced obese Sprague-Dawley rats.

Dairy foods and dietary calcium (Ca) are potential regulators of body weight and insulin sensitivity. The specific components of dairy responsible for these actions are not known but may include leucine. Our objective was to determine the effect of dietary protein (casein, skim milk or leucine) and Ca level [low, 0.67% (LC) or high, 2.4% (HC)] on adiposity and insulin sensitivity. Obesity was induced in Sprague-Dawley rats with a 6-week period of high-fat/high-sucrose (HFHS) diet intake. Rats were randomly assigned to one of six HFHS diets for 8 weeks where dietary protein was provided as casein, skim milk or casein enriched with leucine, and contained either LC or HC. Body composition via dual-energy x-ray absorptiometry and insulin sensitivity via euglycemic-hyperinsulinemic clamp were measured. Microarray was used to assess gene expression in liver and skeletal muscle. Rats fed leucine had greater insulin sensitivity than those fed casein or skim milk (P<.05). Dietary protein differentially regulated hepatic and skeletal muscle genes associated with insulin, peroxisome proliferator-activated receptor and mammalian target of rapamycin pathways. Specifically, two key genes responsible for insulin sensitivity, hepatic insulin receptor substrate (IRS) and protein kinase B (Akt), were altered in hepatic tissue in response to leucine. Rats fed skim milk and leucine diets had lower body weight compared to those fed casein (P<.05). HC reduced fat mass compared to LC (P<.05). While skim milk and leucine both reduced fat mass, only leucine improved insulin sensitivity compared to casein. Differential expression of genes such as IRS and Akt may be responsible for changes in insulin sensitivity in obese rats.

Yellow pea fiber improves glycemia and reduces Clostridium leptum in diet-induced obese rats.

Numerous studies have demonstrated the impact of functional fibers on gut microbiota and metabolic health, but some less well-studied fibers and/or fractions of foods known to be high in fiber still warrant examination. The aim of this study was to assess the effect of yellow pea-derived fractions varying in fiber and protein content on metabolic parameters and gut microbiota in diet-induced obese rats. We hypothesized that the yellow pea fiber (PF) fraction would improve glycemia and alter gut microbiota. Rats were randomized to 1 of 5 isoenergetic dietary treatments for 6 weeks: (1) control; (2) oligofructose (OFS); (3) yellow PF; (4) yellow pea flour (PFL); or (5) yellow pea starch (PS). Glycemia, plasma gut hormones, body composition, hepatic triglyceride content, gut microbiota, and messenger RNA expression of genes related to hepatic fat metabolism were examined. Pea flour attenuated weight gain compared with control, PF, and PS (P < .05). Pea flour, PS, and OFS had significantly lower final percent body fat compared with control. Oligofructose but not the pea fraction diets reduced food intake compared with control (P < .05). Pea fiber resulted in lower fasting glucose and glucose area under the curve compared with control. Changes in gut microbiota were fraction specific and included a decrease in Firmicutes (percent) for OFS, PF, and PFL compared with control (P < .05). The Firmicutes/Bacteroidetes ratio was reduced with OFS, PF, and PFL when compared with PS (P < .05). Taken together, this work suggests that yellow pea-derived fractions are able to distinctly modulate metabolic parameters and gut microbiota in obese rats.

Differential responses of circulating amylin to high-fat vs. high-carbohydrate meal in healthy men

Objective  The success of an amylin analogue in weight loss trials has generated interest in amylin as a physiological satiety signal. Little is known about how plasma amylin responds to macronutrients. This study examined the effects of a high‐carbohydrate meal (CHO), a high‐fat meal (FAT) or a continued fast (FAST) on amylin concentrations and correlations among other satiety hormones and measures of appetite.

Changes in visceral adiposity and serum cholesterol with a novel viscous polysaccharide in Japanese adults with abdominal obesity.

Objective: Evidence supports the role of dietary fiber in improving metabolic health. PolyGlycopleX® (PGX®), a viscous functional polysaccharide improves lipidemia and glycemia in healthy adults. Our objective was to examine the effects of PGX® on risk factors associated with the metabolic syndrome in Japanese adults with abdominal obesity.