scholarly journals Is apolipoprotein A-IV rate limiting in the intestinal transport and absorption of triglyceride?

2013 ◽  
Vol 304 (12) ◽  
pp. G1128-G1135 ◽  
Author(s):  
Alison B. Kohan ◽  
Fei Wang ◽  
Xiaoming Li ◽  
Abbey E. Vandersall ◽  
Sarah Huesman ◽  
...  
Keyword(s):  
Intestinal Mucosa ◽  
Dietary Fat ◽  
Intestinal Transport ◽  
Dietary Lipid ◽  
Lipid Absorption ◽  
Lymphatic Transport ◽  
Apolipoprotein A ◽  
Rate Limiting

Apolipoprotein A-IV (apoA-IV) is synthesized by the intestine and secreted when dietary fat is absorbed and transported into lymph associated with chylomicrons. We have recently demonstrated that loss of apoA-IV increases chylomicron size and delays its clearance from the blood. There is still uncertainty, however, about the precise role of apoA-IV on the transport of dietary fat from the intestine into the lymph. ApoA-IV knockout (KO) mice do not have a gross defect in dietary lipid absorption, as measured by oral fat tolerance and fecal fat measurements. Here, using the in vivo lymph fistula mouse model, we show that the cumulative secretion of triglyceride (TG) into lymph in apoA-IV KO mice is very similar to that of wild-type (WT) mice. However, the apoA-IV KO mice do have subtle changes in TG accumulation in the intestinal mucosa during a 6-h continuous, but not bolus, infusion of lipid. There are no changes in the ratio of esterified to free fatty acids in the intestinal mucosa of the apoA-IV KO, however. When we extended these findings, by giving a higher dose of lipid (6 μmol/h) and for a longer infusion period (8 h), we found no effect of apoA-IV KO on intestinal TG absorption. This higher lipid infusion most certainly stresses the intestine, as we see a drastically lower absorption of TG (in both WT and KO mice); however, the loss of A-IV does not exacerbate this effect. This supports our hypothesis that apoA-IV is not required for TG absorption in the intestine. Our data suggest that the mechanisms by which the apoA-IV KO intestine responds to intestinal lipid may not be different from their WT counterparts. We conclude that apoA-IV is not required for normal lymphatic transport of TG.

scholarly journals Apolipoprotein A-IV regulates chylomicron metabolism–mechanism and function

2012 ◽  
Vol 302 (6) ◽  
pp. G628-G636 ◽  
Author(s):  
Alison B. Kohan ◽  
Fei Wang ◽  
Xiaoming Li ◽  
Suzanne Bradshaw ◽  
Qing Yang ◽  
...  
Keyword(s):  
Dietary Fat ◽  
Cholesterol Metabolism ◽  
Plasma Lipid ◽  
Physiological Role ◽  
Lipid Absorption ◽  
Fat Absorption ◽  
Apolipoprotein A ◽  
And Function ◽  
Dietary Fat Absorption

Dietary fat is an important mediator of atherosclerosis and obesity. Despite its importance in mediating metabolic disease, there is still much unknown about dietary fat absorption in the intestine and especially the detailed biological roles of intestinal apolipoproteins involved in that process. We were specifically interested in determining the physiological role of the intestinal apolipoprotein A-IV (A-IV) using A-IV knockout (KO) mice. A-IV is stimulated by fat absorption in the intestine and is secreted on nascent chylomicrons into intestinal lymph. We found that A-IV KO mice had reduced plasma triglyceride (TG) and cholesterol levels and that this hypolipidemia persisted on a high-fat diet. A-IV KO did not cause abnormal intestinal lipid absorption, food intake, or adiposity. Additionally, A-IV KO did not cause abnormal liver TG and cholesterol metabolism, as assessed by measuring hepatic lipid content, lipogenic and cholesterol synthetic gene expression, and in vivo VLDL secretion. Instead, A-IV KO resulted in the secretion of larger chylomicrons from the intestine into the lymph, and those chylomicrons were cleared from the plasma more slowly than wild-type chylomicrons. These data suggest that A-IV has a previously unknown role in mediating the metabolism of chylomicrons, and therefore may be important in regulating plasma lipid metabolism.

Fructose Phosphorylation and Dephosphorylation by the Intestinal Mucosa of the Rat During Fructose Absorption

1957 ◽  
Vol 189 (2) ◽  
pp. 301-306 ◽  
Author(s):  
Nicholas M. Papadopoulos ◽  
Joseph H. Roe
Keyword(s):  
Intestinal Mucosa ◽  
Phosphate Esters ◽  
Reduction Techniques ◽  
Mucosal Cells ◽  
Normal Metabolism ◽  
Fasted Rats

The role of phosphorylation in the absorption of fructose from the intestinal tract of the fasted rat by in vitro and in vivo techniques was studied. The authors' method for the determination of fructose phosphate esters was used and these esters were identified by paper chromatography and copper reduction techniques. Buffered homogenate of intestinal mucosa of a fasted rat, mixed with ATP, MgCl2, KF and fructose, when incubated at 30°, showed the formation of fructose-6-phosphate and fructose-1, 6-diphosphate at a rate that corresponded to the decrease in free fructose. The same homogenate, mixed with fructose-1, 6-diphosphate and incubated at 37°, showed the formation of fructose-6-phosphate and free fructose at a rate that corresponded to the decrease in the concentration of the diphosphate ester. Following intraduodenal injection of fructose solution into anesthetized fasted rats, homogenates of the intestinal mucosa showed the presence of fructose-6-phosphate and fructose-1, 6-diphosphate in average concentrations 14 and 5 times, respectively, those found in control muocsa, also concentrations of free fructose in the blood of the portal vein up to 24.6 mg % were observed. The large increase in fructose phosphate esters in the intestinal mucosa, observed after fructose administration, suggests that phosphorylation of sugars in absorption serves a more extensive function than to initiate glycolysis for the normal metabolism of the mucosal cells. The data obtained suggest that phosphorylation and dephosphorylation are functional steps in the absorption of fructose from the alimentary tract of the rat.

Influence of vascular and luminal hexoses on rat intestinal basolateral glucose transport

1994 ◽  
Vol 72 (4) ◽  
pp. 317-326 ◽  
Author(s):  
Raymond Tsang ◽  
Ziliang Ao ◽  
Chris Cheeseman
Keyword(s):  
Glucose Transport ◽  
Plasma Glucose ◽  
Intestinal Adaptation ◽  
Basolateral Membrane ◽  
Physiological Role ◽  
Intestinal Transport ◽  
Membrane Vesicles ◽  
Luminal Perfusion

The influence of luminal and vascular hexoses in rats on glucose transport across the jejunal basolateral membrane (BLM) was measured using isolated membrane vesicles prepared from infused animals. In vivo vascular infusions of glucose produced an increase in glucose transport across BLM vesicles. Sucrose, mannose, galactose, and fructose had no significant effect. Plasma glucose concentrations were unaffected by galactose and sucrose vascular infusions, while mannose and fructose produced a modest rise, and glucose increased plasma glucose to 20 mM. Insulin release was significantly increased by vascular infusion of glucose and fructose, while mannose produced only a small sustained rise. Sucrose and galactose had no effect. Perfusion through the lumen of the rat jejunum in vivo, for up to 4 h, with glucose, fructose, sucrose, or lactate (100 or 25 mM) produced a significant increase in the maximal rate of glucose transport (up to 4- to 5-fold) across BLMs. Galactose and mannose had no effect. Luminal glucose perfusion produced a small nonsignificant increase in glucose inhibitable cytochalasin B binding to BLM vesicles, and no change was seen in the microsomal pool of binding sites. The abundance of GLUT2 in the jejunal BLM, as determined by Western blotting, was unaffected by luminal perfusion of 100 mM glucose for 4 h. Fructose almost completely inhibited the carrier-mediated uptake of glucose in control and upregulated jejunal BLM vesicles. These results are discussed in relation to the physiological role of the upregulation of GLUT2 activity by luminal and vascular hexoses.Key words: intestinal transport, basolateral membrane, glucose transport, intestinal adaptation.

Development and Physiological Regulation of Intestinal Lipid Absorption. I. Development of intestinal lipid absorption: cellular events in chylomicron assembly and secretion

2007 ◽  
Vol 293 (3) ◽  
pp. G519-G524 ◽  
Author(s):  
Dennis D. Black
Keyword(s):  
Dietary Fat ◽  
Apolipoprotein B ◽  
Microsomal Triglyceride Transfer Protein ◽  
Lipid Absorption ◽  
Cellular Mechanisms ◽  
Peripheral Tissues ◽  
Physiological Regulation ◽  
Transfer Protein ◽  
Cellular Events ◽  
Apolipoprotein A

The newborn mammal must efficiently absorb dietary fat, predominantly as triacylglycerol, and produce chylomicrons to deliver this lipid to peripheral tissues. The cellular mechanisms involved in enterocyte chylomicron assembly have recently been elucidated, and data on their regulation in the immature gut are beginning to emerge. This review focuses on key proteins involved in chylomicron assembly: apolipoprotein B-48, microsomal triglyceride transfer protein, and apolipoproten A-IV. Recent studies support a role for apolipoprotein A-IV in enhancing chylomicron secretion by promoting production of larger particles. These proteins are regulated in a manner to maximize the lipid absorptive capacity of the newborn intestine.

scholarly journals Lipid Absorption in Adrenalectomized Rats: The Role of Altered Enzyme Activity in the Intestinal Mucosa

1967 ◽  
Vol 53 (4) ◽  
pp. 547-556 ◽  
Author(s):  
John B. Rodgers ◽  
Erla M. Riley ◽  
Gladys D. Drummey ◽  
Kurt J. Isselbacher
Keyword(s):  
Enzyme Activity ◽  
Intestinal Mucosa ◽  
Lipid Absorption ◽  
Adrenalectomized Rats

Vagal control of fluid transport, transmural potential difference, and motility in the ferret jejunum

1985 ◽  
Vol 249 (6) ◽  
pp. G651-G654 ◽  
Author(s):  
B. Greenwood ◽  
N. W. Read
Keyword(s):  
Fluid Transport ◽  
Vagal Stimulation ◽  
Contractile Activity ◽  
Intestinal Transport ◽  
Intestinal Secretion ◽  
Potential Difference ◽  
Intraluminal Pressure ◽  
Jejunal Loop

The role of the vagus nerve in the control of intestinal transport was investigated in the ferret jejunum in vivo. Fluid transport was measured in an isolated 10-cm segment of jejunum by means of a single-pass perfusion technique with radioactive markers introduced into the perfusion fluid and the bloodstream of the animal. Transmural potential difference (PD) and intraluminal pressure in the perfused jejunal loop were also monitored. Vagal stimulation (20 Hz, 20 V, and 0.5 ms for 1 min) resulted in jejunal fluid movement in the direction of secretion, a rise in transmural PD, and an increase in jejunal contractile activity. Similar changes were induced by close intra-arterial injection of acetylcholine (20 micrograms X kg-1). The contractile response to vagal stimulation was abolished by atropine. Moreover, atropine did not block the changes in fluid transport and transmural PD that were induced by vagal stimulation, although the transmural PD response was reduced. The results suggest that vagal stimulation induces intestinal secretion accompanied by a rise in transmural PD; the events are mediated at least in part by a noncholinergic transmitter as yet undetermined.

Intestinal aspects of lipid absorption: in review

1989 ◽  
Vol 67 (3) ◽  
pp. 179-191 ◽  
Author(s):  
A. B. R. Thomson ◽  
M. Keelan ◽  
M. L. Garg ◽  
M. T. Clandinin
Keyword(s):  
Dietary Fat ◽  
De Novo ◽  
Membrane Lipid ◽  
Dietary Fats ◽  
Lipid Absorption ◽  
Limiting Factor ◽  
Adaptive Responses ◽  
Phospholipid Biosynthesis ◽  
New Knowledge ◽  
Rate Limiting

The rapidly evolving field of lipid absorption is reviewed with the thrust of new knowledge focused on the interpendency of the luminal and cellular phases of absorption. To date little attention has been paid to factors that regulate the phospholipid biosynthesis in the enterocyte. The availability of 20:4ω6 may be the rate-limiting factor for phospholipid synthesis. The source of 20:4ω6 is unknown, whether it be synthesized de novo the enterocyte or entirely originating from degradation of bile phospholipid. It has been established that dietary fat can modulate the enterocyte membrane lipid composition and transport properties. Specified fats such as as fish oils rich in 20:5ω3 and 22:6ω3 have been implicated as protective against hypercholesterolemia. However, the effects of these dietary fats on the transport of nutrients across the enterocyte are not yet known, nor are the mechanisms responsible for the adaptive responses of the brush border identified.

Mechanisms responsible for increasing immunoreactivity of apolipoprotein A-I with storage: the role of oxidation.

1989 ◽  
Vol 35 (10) ◽  
pp. 2082-2086 ◽  
Author(s):  
X L Wang ◽  
N P Dudman ◽  
J Wang ◽  
D E Wilcken
Keyword(s):  
Density Lipoprotein ◽  
Polyclonal Antiserum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Carrier Protein ◽  
Nonspecific Binding ◽  
Apolipoprotein A ◽  
Low Concentrations ◽  
Peroxidase Conjugate

Abstract Atherogenesis has been linked to low concentrations of high-density lipoprotein and its principal carrier protein, apolipoprotein (apo) A-I, in serum. We measured apo A-I by enzyme-linked immunosorbent assay, using polyclonal antiserum raised against purified apo A-I and conjugated to peroxidase. During storage at 4 degrees C and above, the immunoreactivity of apo A-I increased so that measured values in stored serum were difficult to interpret. The immunoreactivity of serum apo A-I also increased substantially (up to 50-fold) during exposure to NaIO4. This increase was apo A-I concentration dependent, was linearly dependent on the concentration of NaIO4 up to 200 mmol/L at pH 7.4 and 25 degrees C, and was not ascribable to nonspecific binding of antibody-peroxidase conjugate to the reaction wells. Treatment with NaIO4 caused apo A-I immunoreactivity to increase to a peak or plateau, then gradually decline. In 100 mmol/L NaIO4 (pH 7.4, 25 degrees C), this plateau occurred 30-60 min after oxidation commenced. When frozen serum and stored nonfrozen serum were both oxidized with NaIO4 under the same conditions, the apo A-I from the frozen serum had a significantly (P = 0.0004) greater increase in immunoreactivity. Sera from different patients with different apo A-I concentrations did not have proportionately increased immunoreactivity after treatment with NaIO4. Our findings suggest that the increase in apo A-I immunoreactivity on storage at 4 degrees C or higher involves atmospheric oxidation, and they raise the possibility of in vivo oxidized and nonoxidized forms of apo A-I.

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