Fat Bolus Research Articles

Comparison of a Standardized High-Fat Meal versus a High-Fat Meal Scaled to Body Mass for Measuring Postprandial Triglycerides: A Randomized Crossover Study.

Post-meal triglycerides are an independent cardiovascular disease (CVD) risk factor, but the ideal high-fat meal formulation has yet to be standardized and is one challenge prohibiting widespread clinical adoption of postprandial triglyceride assessment. Two general approaches often used are giving individuals a high-fat meal scaled to body weight or a standardized high-fat meal containing a set fat bolus. A recent expert panel statement has endorsed the latter, specifying 75 g of fat as an appropriate fat dosage. Despite this recommendation, no study to date has tested whether there is a difference in postprandial triglycerides or if risk classification is affected based on these different approaches. We recruited 16 generally healthy individuals with roughly equal distribution among body mass index (BMI)class (n = 5–6/per BMI category) and sex (n = 2–3 M/F) within each BMI class. Each participant underwent two abbreviated fat tolerance tests separated by ~1 week: one with a scaled to body weight high-fat meal (9 kcal/kg; 70% fat) and a standardized meal containing 75 g of fat (70% fat). Fasting, 4 h, and absolute change in triglycerides across the entire sample and within each BMI category were similar regardless of high-fat meal. Only one participant with obesity had discordant postprandial responses between the fat tolerance tests (i.e., different CVD risk classification). These findings suggest that, within a certain range of fat intake, generally healthy individuals will have a similar postprandial triglyceride response. Considering the greater convenience of utilizing standardized high-fat meals, our data suggest that a standardized high-fat meal may be acceptable for large-scale studies and clinical implementation.

VEGFR-3 Signaling Regulates Triglyceride Retention and Absorption in the Intestine.

The lymphatic system transports dietary lipids absorbed and packaged as chylomicrons by enterocytes, for delivery to the bloodstream. Once considered a passive drainage, chylomicron entry into intestinal lymphatic vessels, or lacteals, is now emerging to be an active process controlled by a dynamic and complex regulation. Vascular endothelial growth factor (VEGF)-C, a major lymphangiogenic factor, regulates lacteal maintenance and function. Little is known about the role of its cognate tyrosine kinase VEGF receptor 3 (VEGFR-3) during lipid absorption. Here we investigated role of VEGFR-3 signaling in triglyceride (TG) absorption and distribution into tissues using the Chy mouse model, which bears an inactivating mutation in the tyrosine kinase domain of VEGFR-3 (heterozygous A3157T mutation resulting in I1053F substitution). Our data show that inactivation of VEGFR-3 tyrosine kinase motif leads to retention of TGs in the enterocytes of the small intestine, decreased postprandial levels of TGs in the plasma and increased excretion of free fatty acids (FFAs) and TGs into their stools. We further show that levels of nitric oxide (NO), required for chylomicron mobilization into the bloodstream, are significantly reduced in the Chy intestine after a fat bolus suggesting a critical role for VEGFR-3 signaling in the generation of NO during lipid absorption. Our data support the hypothesis that VEGFR-3 signaling plays an important role in chylomicron-TG entry into lacteals, possibly affecting TG trafficking to peripheral tissues.

Out of the frying pan: dietary saturated fat influences nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess accumulation of fat in the liver. In some cases, NAFLD is also accompanied by insulin resistance, resulting in metabolic dysfunction. Dietary fat content probably influences both NAFLD and insulin resistance; however, the immediate effects of fat consumption have not been fully explored. In this issue of the JCI, Hernández et al. evaluated hepatic glucose and lipid metabolism in humans and mice following a single oral dose of saturated fat. This one bolus of fat resulted in a measurable increase in insulin resistance, hepatic triglycerides, and gluconeogenesis. In mice, the saturated fat bolus resulted in the induction of several NAFLD-associated genes. Together, the results of this study indicate that saturated fat intake has immediate effects on metabolic function.

Fat Bolus Impaction; a Rare Case Report

An impacted esophageal foreign body is most often an urgent, rather than a life-threatening, medical situation. Typically, two types of foreign bodies are encountered: true foreign bodies (buttons, coins, pieces of balloon etc) and food-related foreign bodies. Ingestion of true foreign bodies generally occurs in persons less than 40 years old, with the vast majority being children. The incidence of true foreign body ingestion is also high in incarcerated individuals and in persons with psychiatric disorders. Food-related foreign bodies are more prevalent in persons who are over 60 years of age, who have esophageal disease, anatomic narrowing, motility disorders or who have recently consumed central nervous system depressants, especially ethanol. This article describes the clinical presentation, radiological findings and management of impacted mutton fat bolus as foreign body in an adult male patient.

CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood

CD36 mediates the transfer of fatty acids (FAs) across the plasma membranes of muscle and adipose cells, thus playing an important role in regulating peripheral FA metabolism in vivo. In the proximal intestine, CD36 is localized in abundant quantities on the apical surface of epithelial cells, a pattern similar to that of other proteins implicated in the uptake of dietary FAs. To define the role of CD36 in the intestine, we examined FA utilization and lipoprotein secretion by WT and CD36-null mice in response to acute and chronic fat feeding. CD36-null mice given a fat bolus by gavage or fed a high-fat diet accumulated neutral lipid in the proximal intestine, which indicated abnormal lipid processing. Using a model in which mice were equipped with lymph fistulae, we obtained evidence of defective lipoprotein secretion by directly measuring lipid output. The secretion defect appeared to reflect an impaired ability of CD36-null enterocytes to efficiently synthesize triacylglycerols from dietary FAs in the endoplasmic reticulum. In the plasma of intact mice, the reduced intestinal lipid secretion was masked by slow clearance of intestine-derived lipoproteins. The impaired clearance occurred despite normal lipoprotein lipase activity and likely reflected feedback inhibition of the lipase by FAs due to their defective removal from the plasma. We conclude that CD36 is important for both secretion and clearance of intestinal lipoproteins. CD36 deficiency results in hypertriglyceridemia both in the postprandial and fasting states and in humans may constitute a risk factor for diet-induced type 2 diabetes and cardiovascular disease.

CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood

CD36 mediates the transfer of fatty acids (FAs) across the plasma membranes of muscle and adipose cells, thus playing an important role in regulating peripheral FA metabolism in vivo. In the proximal intestine, CD36 is localized in abundant quantities on the apical surface of epithelial cells, a pattern similar to that of other proteins implicated in the uptake of dietary FAs. To define the role of CD36 in the intestine, we examined FA utilization and lipoprotein secretion by WT and CD36-null mice in response to acute and chronic fat feeding. CD36-null mice given a fat bolus by gavage or fed a high-fat diet accumulated neutral lipid in the proximal intestine, which indicated abnormal lipid processing. Using a model in which mice were equipped with lymph fistulae, we obtained evidence of defective lipoprotein secretion by directly measuring lipid output. The secretion defect appeared to reflect an impaired ability of CD36-null enterocytes to efficiently synthesize triacylglycerols from dietary FAs in the endoplasmic reticulum. In the plasma of intact mice, the reduced intestinal lipid secretion was masked by slow clearance of intestine-derived lipoproteins. The impaired clearance occurred despite normal lipoprotein lipase activity and likely reflected feedback inhibition of the lipase by FAs due to their defective removal from the plasma. We conclude that CD36 is important for both secretion and clearance of intestinal lipoproteins. CD36 deficiency results in hypertriglyceridemia both in the postprandial and fasting states and in humans may constitute a risk factor for diet-induced type 2 diabetes and cardiovascular disease.

Screening of stimulatory effects of dietary risk factors on mouse intestinal cell kinetics.

Although epidemiological and experimental studies validate influence of genetic, environmental and dietary factors in the causation of various types of cancers including colon, results from all these sources are inconclusive. Hypothesizing that high fat diet and obesity are among the major predisposing factors in the incidence of colon cancer, we evaluated the role of diet constituted with food material derived from a tropical plant, Tamarindus indica Linn (TI). A two part randomized double-blind study was conducted employing inbred Swiss albino mice from a single generation for the whole investigation. One day-old neonates (n = 12) were subcutaneously administered with monosodium glutamate (MSG) to induce obesity (OB). At weaning these animals were maintained on modified AIN-76 diet supplemented with 10% TI and 10% fat bolus (w/w, TIFB) for 8 wk. Subsequently, in the second part of study, four groups of animals belonging to the same generation, age and gender (n = 12 per group), were maintained on: AIN-76 control diet (CD); AIN-76 mixed with 10% TI extract (TI); and, mixed with 10% TI and 10% FB (TIFB) for 8 wk, to determine intestinal crypt cell proliferation, functionally-specific enzyme activities, fermentation profile, and energy preferences. We observed a significant increase in the crypt cell production rate in distal colonic segment of experimental animals when compared with the controls. This segment also contained significantly low butyrate levels compared to control and TIFB groups. All the experimental groups showed a gross decrease in the enzyme activities viz., succinate dehydrogenase, acid-galactosidase and dipeptidyl amino peptidase IV demonstrating pathological stress caused by the test regimens, and an altered metabolic flux in the cellular environment. We have demonstrated a cumulative response to the three dietary factors, one of which (TI) is reported, herein, for the first time to modulate kinetics of large intestinal mucosa, contributing to total risk posed by these test agents.

Feeding Minipigs Fish Oil for Four Weeks Lowers Postprandial Triacylglycerolemia

We wanted to establish a minipig model for the study of postprandial lipemia and plasma lipid clearance after fish oil consumption. Seven minipigs were fed a fish oil-enriched nonpurified diet and a control diet for 4 wk in a randomized cross-over study. After each intervention period, each pig was challenged with a gastric fat load (2 g fat/kg body) and an intravenous fat bolus (0.1 g/kg body) on separate days. Frequent blood samples were collected for 6 h after the gastric fat load and for 40 min after the intravenous bolus. The fish oil-enriched diet was associated with lower triacylglycerol, glycerol and nonesterified fatty acid concentrations in the hours after the gastric fat load than the control diet (P < 0.05). In contrast, the triacylglycerol disappearance rate after the intravenous fat bolus was not affected by fish oil (P = 0.19). In conclusion, dietary fish oil supplementation attenuates postprandial lipemia in minipigs similarly to what occurs in humans. Minipigs could serve as a useful model for future studies of this phenomenon. We observed no significant effect of fish oil supplementation on plasma triacylglycerol clearance and thus were unable to identify the mechanism explaining the attenuated lipemia in minipigs.

Effects of growth hormone administration on the body composition and hormone levels of genetically fat sheep

AbstractCoopworth sheep selected for low (lean) or high (fat) backfat have large differences in plasma GH profiles. Fat genotype ram lambs (5 months old) were treated with growth hormone (GH) to simulate the plasma GH profiles of lean sheep and investigate whether exogenous GH could modify carcass fatness. For 77 days, bovine GH was administered at 25 Uglkg live weight per day either as a single, daily subcutaneous bolus (fat bolus) or via portable pulsatile infusion pumps (fat pump) which delivered GH solution at 90-min intervals into a jugular catheter. Measurements of body composition were made by computed tomography (CT) and ultrasonic scanning during the trial, with linear carcass measurements and proximate analysis undertaken at the end of the experiment.Before treatments began, mean plasma GH levels were lower (P &lt; 0·01) in fat control (0·34 ugll) than in lean lambs (1·1 μg/l). Several weeks after the start of the trial, mean plasma GH had increased in both fat bolus (1·2 μg/l) and fat pump (0·45 μg/l) treatment lambs with major changes in the pulsatility relative to the fat control lambs. Although these changes were maintained in the fat bolus lambs, by the end of the trial there was no significant difference in mean plasma GH between fat pump and fat control sheep. Throughout the trial, plasma 1GF-1 levels were higher in fat bolus, fat pump and lean lambs than in fat control lambs. Analysis of body composition data over the GH treatment period revealed that the slope of the allometric equation for total fat relative to empty body weight was lower in the fat bolus lambs (1·07) than in the lean lambs (1·50) with fat control and fat pump treatment lambs intermediate (1·30 and 1·36, respectively). Subcutaneous fat was later maturing in lean lambs than in fat control and bolus treatment lambs when regressed against total fat, with the fat pump treatment lambs being intermediate. Linear carcass measurements revealed changes due to GH administration in the distribution of subcutaneous fat and eye muscle dimensions.It is concluded that sheep from the fat genotype show physiological responses to exogenous GH. Increasing plasma GH levels of fat sheep increased plasma IGF-1 and had variable effects on carcass fatness. The change in body composition may be affected by the mode of administration of exogenous GH.

667 L-CARNITINE ON FAT UTILIZATION IN INFANTS

L-carnitine (LC), which is essential for fat utilization, acts by facilitating long chain fatty acid transport into the mitochondrial matrix where B-oxidation occurs. The purpose of this prospective study was to determine if LC supplementation given to carnitine deficient infants would results in improved utilization of exogenously administered IV fat. Seventeen infants (gestational age 35.8±3.7 wks, postnatal age 13.6±7.3 wks, weight 3.3±1.0 kg) requiring a minimum of 7 days of parenteral nutrition (PN) and able to tolerate small quantities of enteral feedings were randomized into treatment and control groups. All infants had received nutritional support devoid of LC. Plasma carnitine (PC) levels did not vary significantly between groups in the pre-study period (control: 10.0±6.3 nM/ml; treatment: 9.4±6.0 nM/ml). Infants received 7 days of continuous nasogastric or gastric tube LC (50uM/k/d) or placebo. Fat was withheld and glucose reduced to 10% for 16 hrs prior to the delivery of a 0.5 gm/k IntralipidR bolus administered over 2 hrs. LC supplementation continued until termination of the fat bolus. Serial blood samples for triglycerides (TGY), free fatty acids (FFA), acetoacetate (AA), B-hydroxybutyrate (BOB) and PC were observed at 0 (start of lipid infusion), 2,4,6 and 8 hrs. Infants receiving carnitine had significantly greater (p<0.05) concentrations of BOB, total ketones (BOB plus AA), and PC at times 0,2,4,6 and 8 hrs when compared to controls. Significantly lower (p<0.05) FFA/BOB ratios were observed in the treatment group at 2 and 4 hours indicating improved ketogenesis. No significant differences were found between groups for TGY or FFA at any observation period. This study demonstrated improved fatty acid oxidation as evidenced by increased ketogenesis with LC supplementation in carnitine deficient infants.

Changes in fat concentration of human milk during delivery by intermittent bolus and continuous mechanical pump infusion

The changes in fat concentration and cumulative fat losses that occur during the delivery of human milk using two different continuous infusion systems were compared with the changes in fat concentration during simulated intermittent gavage or bolus feedings. With both mechanical pumps the largest cumulative fat losses and the greatest decreases in fat concentrations occurred at the slowest infusion rates. State of homogenization of the milk generally made little difference in the changes in fat concentration using the syringe pump, whereas homogenizing the milk increased the fat concentration significantly with the roller pump. With the syringe pump the positioning of the syringe tip (horizontal or vertical) made no difference in fat concentration at an infusion rate of 1 ml/hr, whereas at 4 and 7 ml/hr the fat concentration was increased significantly by keeping the syringe tip vertical. With either mechanical pump a large fat bolus was delivered during the eighth and final hour of infusion if the milk remaining in the tubing was recovered by using air infusion at the same infusion rate. Intermittent bolus delivery of human milk resulted in no significant loss of human milk fat, no changes in fat concentration, and no terminal delivery of a large fat load. Thus intermittent bolus feedings are preferred over continuous mechanical pump infusion systems for the delivery of human milk to low-birth-weight infants.

CHANGES IN FAT CONCENTRATION OF HUMAN MILK WITH;' CONTINUOUS MECHANICAL PUMP INFUSION VERSUS INTERMITTENT BOLUS DELIVERY

We studied changes in fat conc. and fat loss in human milk during 8 hr continuous infusion with 2 mechanical pumps (Harvard syringe [HARV] and Holter roller [HOLT] with Buretrol) and for comparison intermittent bolus delivery. We varied rate of pump infusion (1,4 or 7 ml/hr), state of homogenization and syringe position (HARV, tip vert or horiz). For each set of variables, infusions were repeated x4. Hourly samples were analyzed for fat. Infusion apparatus held only enough milk for an 8 hr. infusion, milk in the tubing being recovered by air infusion at the same rate. At 1 ml/hr with HARV and HOLT, 26-39% of fat was lost regardless of conditions. Fat conc. during infusion decreased to 32% of baseline for HARV and to 2% for HOLT, regardless of syringe position (HARV) or homogenization. During the 8th hr of infusion a large fat bolus was delivered (240±74% HARV & 435±131% HOLT > baseline fat conc). At 4 and 7 ml/hr fat losses for HARV and HOLT were 1-23% & 5-31% respectively and fat conc. decreased to 30-70% of baseline for HARV and 5-40% for HOLT. A large fat bolus was delivered during the 8th hr of infusion (144-333% HARV, 277-567% HOLT > baseline fat conc). Homogenization made no difference. For HARV changes in fat conc. could be decreased 12-22% by keeping syringe tip vert. With intermittent bolus delivery of milk (1,4,7 ml) no loss of fat, change in fat conc., or fat bolus occurred. Thus, for NG delivery of human milk to LBW infants, intermittent bolus is preferred. Continuous NG pump infusion should not be used because of large changes in fat conc. and fat loss.