Chronic high-fat diet affects intestinal fat absorption and postprandial triglyceride levels in the mouse

The effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive. It is unknown whether a fat-mediated adaptation to lipid absorption takes place. To address this issue, mice fed a high-fat diet (40%, w/w) were refed or not a control diet (3%, w/w) for 3 additive weeks. Despite daily lipid intake 7.7-fold higher than in controls, fecal lipid output remained unchanged in mice fed the triglyceride (TG)-rich diet. In situ isolated jejunal loops revealed greater [1-(14)C]linoleic acid uptake without TG accumulation in mucosa, suggesting an increase in lipid absorption capacity. Induction both in intestinal mitotic index and in the expression of genes involved in fatty acid uptake, trafficking, and lipoprotein synthesis was found in high-fat diet mice. These changes were lipid-mediated, in that they were fully abolished in mice refed the control diet. A lipid load test performed in the presence or absence of the LPL inhibitor tyloxapol showed a sustained blood TG clearance in fat-fed mice likely attributable to intestinal modulation of LPL regulators (apolipoproteins C-II and C-III). These data demonstrate that a chronic high-fat diet greatly affects intestinal physiology and body lipid use in the mouse.     

Importance of changes in gastric emptying for postprandial plasma glucose fluxes in healthy humans

Angiotensin II (Ang II) stimulation of the Ang type 1 receptor (AT(1)R) facilitates myocardial remodeling through NADPH oxidase-mediated generation of oxidative stress. Components of the renin-angiotensin system constitute an autocrine/paracrine unit in the myocardium, including renin, which is the rate-limiting step in the generation of Ang II. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo renin inhibition and/or AT(1)R blockade in a rodent model of chronically elevated tissue Ang II levels, the transgenic (mRen2)27 rat (Ren2). The Ren2 overexpresses the mouse renin transgene with resultant hypertension, insulin resistance, and cardiovascular damage. Young (6- to 7-wk-old) heterozygous (+/-) male Ren2 and age-matched Sprague-Dawley rats were treated with the renin inhibitor aliskiren, which has high preferential affinity for human and mouse renin, an AT(1)R blocker, irbesartan, or placebo for 3 wk. Myocardial NADPH oxidase activity and immunostaining for NADPH oxidase subunits and 3-nitrotyrosine were evaluated and remodeling changes assessed by light and transmission electron microscopy. Blood pressure, myocardial NADPH oxidase activity and subunit immunostaining, 3-nitrotyrosine, perivascular fibrosis, mitochondrial content, and markers of activity were significantly increased in Ren2 compared with SD littermates. Both renin inhibition and blockade of the AT(1)R significantly attenuated cardiac functional and structural alterations, although irbesartan treatment resulted in greater reductions of both blood pressure and markers of oxidative stress. Collectively, these data suggest that both reduce changes driven, in part, by Ang II-mediated increases in NADPH oxidase and, in part, increases in blood pressure.     

Association of serum adiponectin concentration to lipid and glucose metabolism in healthy humans.

BACKGROUND: Adiponectin is a recently discovered plasma protein with many associations to glucose and lipid metabolism. Due to its central role in cardiovascular diseases and insulin resistance, we studied the relationship between serum adiponectin and factors reflecting glucose and lipid metabolism. METHODS AND RESULTS: Thirty healthy participants (20M/10F, age 32.0 +/- 2.1 years, BMI 25.8 +/- 0.9 kg/m (2) and HbA (1c) 5.2 +/- 0.1 %) were studied four times at approximately one week intervals. The effects of a 4-hour euglycemic hyperinsulinemia (40 mU/m (2)/min), saline infusion (control), oral glucose, and oral fat load on serum adiponectin were studied. No significant correlation was found between serum adiponectin and insulin sensitivity before (r = 0.25) or after adjustment for age, BMI and gender (r = 0.04). Adiponectin concentration correlated inversely with HbA (1c) (r = - 0.43, p < 0.05), insulin concentration (r = - 0.38, p < 0.05) and triglyceride concentration (r = - 0.42, p < 0.05) but positively with HDL cholesterol (r = 0.38, p < 0.05). Metabolic procedures had no effect on serum adiponectin. CONCLUSIONS: Our findings favor the interpretation that adiponectin is not causally related to insulin sensitivity in healthy participants. The strongest associations of adiponectin in healthy participants are to be found to lipid metabolism. Serum levels of adiponectin are very stable and not acutely affected by hyperinsulinemia, oral glucose or fat load.     

Effect of small intestinal glucose load on plasma ghrelin in healthy men

Postprandial ghrelin suppression arises from the interaction of meal contents with the small intestine and may relate to elevations in blood glucose and/or plasma insulin. We sought to determine whether the suppression of ghrelin by small intestinal glucose is dependent on the glucose load and can be accounted for by changes in blood glucose and/or plasma insulin. Blood glucose, plasma insulin, and plasma ghrelin levels were measured in 10 healthy males (aged 32+/-4 yr; body mass index: 25.1+/-0.4 kg/m2) during intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2), and 4 kcal/min (G4), as well as intraduodenal hypertonic saline (control) for 120 min. There was a progressive decrease in ghrelin with all treatments, control at 45 min and between 90 and 120 min (P<0.05) and G1 (P<0.05), G2 (P<0.0001), and G4 (P<0.0001) between 30 and 120 min to reach a plateau at approximately 90 min. There was no difference in plasma ghrelin between G1, G2, or G4. Control suppressed ghrelin to a lesser extent than intraduodenal glucose (P<0.05). The suppression of ghrelin was not related to rises in blood glucose or plasma insulin. Suppression of ghrelin by intraduodenal glucose in healthy males is apparently independent of the glucose load and unrelated to blood glucose or insulin levels.     

Suppressive effects of dietary fiber in yogurt on the postprandial serum lipid levels in healthy adult male volunteers

This study assessed the effect of partially hydrolyzed guar gum (PHGG) in yogurt on the elevation of postprandial serum lipid levels. Eleven healthy adult male subjects were given yogurt with or without 6 g of PHGG in a fat tolerance test as a crossover study. Supplementation with 6 g of PHGG significantly suppressed the incremental peaks and areas under the incremental curve (AUIC) of postprandial serum remnant-like lipoprotein particle cholesterol (RLP-C) and triglyceride (TG). The results suggest the potential of PHGG to reduce the risk of hyperlipemia.     

Regional specificity of the gut-incretin response to small intestinal glucose infusion in healthy older subjects

The importance of the region, as opposed to the length, of small intestine exposed to glucose in determining the secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) remains unclear. We sought to compare the glycemic, insulinemic and incretin responses to glucose administered to the proximal (12–60 cm beyond the pylorus), or more distal ( > 70 cm beyond the pylorus) small intestine, or both. 10 healthy subjects (9M,1F; aged 70.3 ± 1.4 years) underwent infusion of glucose via a catheter into the proximal (glucose proximally; GP), or distal (glucose distally; GD) small intestine, or both (GPD), on three separate days in a randomised fashion. Blood glucose, serum insulin and plasma GLP-1, GIP and CCK responses were assessed. The iAUC for blood glucose was greater in response to GPD than GP (P < 0.05), with no difference between GD and GP. GP was associated with minimal GLP-1 response (P = 0.05), but substantial increases in GIP, CCK and insulin (P < 0.001 for all). GPD and GD both stimulated GLP-1, GIP, CCK and insulin (P < 0.001 for all). Compared to GP, GPD induced greater GLP-1, GIP and CCK responses (P < 0.05 for all). Compared with GPD, GD was associated with greater GLP-1 (P < 0.05), but reduced GIP and CCK (P < 0.05 for both), responses. We conclude that exposure of glucose to the distal small intestine appears necessary for substantial GLP-1 secretion, while exposure of both the proximal and distal small intestine result in substantial secretion of GIP.     

Effects of glucose ingestion on postprandial lipemia and triglyceride clearance in humans

To determine whether the metabolism of diet-derived triglycerides (TG) is acutely regulated by the consumption of insulinogenic carbohydrates, we measured the effects of glucose ingestion on oral and intravenous fat tolerance, and on serum triglyceride concentrations obtained during duodenal fat perfusion. Postprandial lipemia was diminished by the ingestion of 50 g (148 +/- 121 mg.dl-1 x 7 h-1 vs 192 +/- 124 mg.dl-1 x 7 h-1, P less than 0.05) and 100 g (104 +/- 106 mg.dl-1 x 7 h-1 vs 171 +/- 104 mg.dl-1 x 7 h-1, P less than 0.05) glucose. Peak postprandial TG concentrations occurred later after meals containing glucose and fat than after meals containing fat alone. This effect could be reproduced when an iso-osmotic quantity of urea was substituted for glucose in the test meal. Starch ingestion had no discernible effect on postprandial lipemia. Intravenous fat tolerance was similar before (4.9 +/- 1.2%.min-1) and 2 h (4.4 +/- 1.3%.min-1) and 4 h (4.8 +/- 1.5%.min-1) after 50 g glucose ingestion. During duodenal fat perfusion, glucose ingestion caused a progressive decrease in plasma triglyceride concentrations. These data suggest that glucose ingestion diminishes postprandial lipemia in a dose-dependent manner, but that this effect is not due to increased clearance of triglyceride from the circulation. The hypotriglyceridemic effects of glucose appear to reflect delayed gastric emptying and decreased hepatic secretion of triglyceride.     

Effect of ethanol on intestinal lipid absorption in the rat

The effect of ethanol infusion on intestinal lipid absorption was studied in rats with a duodenal cannula. Rats were infused with ethanol overnight and ethanol was included in a trioleoylglycerol emulsion infusion given for 3 hr the next day. These rats were compared to control animals infused with glucose (isocalorically). The ethanol-infused rats had a greatly impaired lipid absorptive capacity. The monoacylglycerol and free fatty acid contents in the intestinal lumen in the ethanol-infused rats were 4- and 7-fold greater, respectively, than controls. The inhibition of absorption was not due to an effect of ethanol on lipolytic activity. The lipase content of the ethanol-infused rats was greater than controls and the separate infusion of monoacylglycerol and fatty acids demonstrated impaired absorption of these end products of lipolysis as compared to controls. To observe if these changes were due to an effect of ethanol on the enterocyte brush border membrane, the membrane lipids were analyzed. The phosphatidylcholine, lysophosphatidylcholine, and phosphatidylethanolanine content was reduced but not the neutral lipids, sphingomyelin, or phosphatidylserine. The uptake of fatty acid into intestinal rings was also shown to be impaired by ethanol infusion. Lastly, the specific activity of the neutral lipids remaining in the intestinal lumen after [3H]glycerol-labeled trioleoylglycerol-infusion was similar to controls even though the mass was much greater. It is concluded that ethanol impairs neutral lipid absorption due to an effect on the enterocyte brush border membrane and by increasing the efflux of low specific activity lipid from the enterocyte back out into the intestinal lumen. A potential pathway for this efflux is the recently described increased porosity of the apical junctional complex in response to ethanol infusion.     

Ultrastructural localization of acid phosphatase activity in the small intestinal absorptive cells of adult rats

Summary Ultrastructural localization of acid phosphatase activity was investigated in ultrathin (0.05 m) and semithin (0.5 and 0.75 m) sections of the small intestinal epithelial cells of adult rats. The results showed that the enzyme activity was localized on the membrane of microvilli, lateral cell membranes, lysosomes, the Golgi complex, and the GERL of Novikoff (a part of the smooth-surfaced endoplasmic reticulum located in close proximity to the inner Golgi saccules) of duodenal absorptive cells. The lysosomes contained within the duodenal and jejunal absorptive cells appeared to be mainly heterolysosomes rather than autolysosomes. The enzyme activity of absorptive cells was lower in the jejunum than in the duodenum, and was barely detectable except in the GERL and lysosomes of the ileum. The average numbers of lysosomes having a diameter of 0.21.0 m, per cell profile in sections of 214 duodenal, 226 jejunal and 318 ileal epithelial cells were 8.9±0.189, 6.4±0.155 and 3.5±0.027 (mean±SE), respectively. From these results, it was assumed that both the Golgi apparatus and GERL produce some lysosomes in the duodenal and jejunal absorptive cells, but only GERL does so in the ileum. It was considered also that because of an unexpectedly high number of lysosomes contained within the epithelial absorptive cells of the proximal intestine of adult rats, these cells may possess the strong heterophagic, as well as absorptive capacity.     

Effect of bread containing resistant starch on postprandial blood glucose levels in humans

We examined the inhibitory effect of a single ingestion of bread containing resistant starch (bread containing about 6 g of resistant starch derived from tapioca per 2 slices) (test food) on the postprandial increase in blood glucose in male and female adults with a fasting blood glucose level between 100 and 140 mg/dl. Bread not containing resistant starch (placebo) was used as the control.The study was conducted in 20 subjects (9 men and 11 women with a mean age of 50.5+/-7.5 years) using the crossover method, with a single ingestion of either bread containing resistant starch or the placebo. Blood glucose and insulin were measured before ingestion, and at 0.5, 1, 1.5, and 2 h after ingestion. The blood glucose level before ingestion was stratified into a borderline group (blood glucose level >/= 111 mg/dl) and a normal group (blood glucose level 相似文献   

Relations of serum interleukin 18 levels to serum lipid and glucose concentrations in an apparently healthy adult population

AIM: To investigate the associations between serum interleukin (IL) 18 concentrations and indices of lipid and carbohydrate metabolism in healthy adults. METHODS: Fasting serum concentrations of IL-18, glucose, total cholesterol, triglyceride, and high- and low-density lipoprotein cholesterols were measured in 570 apparently healthy adults. RESULTS: Univariate linear and partial regression analyses showed that the serum IL-18 concentration was positively correlated with serum triglyceride and glucose concentrations in both obese and diabetic subjects after controlling for the confounding effects of age, sex, and body mass index. CONCLUSION: IL-18 may be associated with obesity and glucose intolerance.