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.

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 Study of Antiobesity Effect through Inhibition of Pancreatic Lipase Activity ofDiospyros kakiFruit andCitrus unshiuPeel

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Gyo-Nam Kim ◽  
Mi-Rae Shin ◽  
Sung Ho Shin ◽  
Ah Reum Lee ◽  
Joo Young Lee ◽  
...  
Keyword(s):  
Pancreatic Lipase ◽  
Lipase Activity ◽  
Dietary Fat ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Diospyros Kaki ◽  
Fat Absorption ◽  
Dietary Fat Absorption

Pancreatic lipase is the enzyme responsible for digestion and absorption of triglycerides, being its inhibition one of the widest studied methods used to determine the potential activity of natural products to inhibit dietary fat absorption. Decrease of energy intake from dietary fat through inhibition of this enzyme may be an excellent strategy to prevent and treat obesity. The inhibitory activity on pancreatic lipase enzyme ofDiospyros kakifruit andCitrus unshiupeel mixture extract (PCM) was evaluatedin vitroand its antiobesity effects were studied based on the serum lipid parameters analysis from high-fat diet- (HFD-) fed micein vivo. PCM was orally administered at a dose of 50 and 200 mg/kg body weight for 6 weeks. In addition, the activity of pancreatic lipase was assessed using orlistat (positive control). PCM exhibited inhibitory effect on lipase activity with IC50value of 507.01 μg/mL. Moreover, serum triacylglycerol, total cholesterol levels, and visceral fat weight were significantly reduced compared to HFD control mice in PCM 200 mg/kg-treated mice (p<0.05). These results suggest that PCM administration may be a novel potential antiobesity agent for reduction of fat absorption via inhibition of pancreatic lipase.

Effect of diet on triolein absorption in weanling rats

1990 ◽  
Vol 258 (1) ◽  
pp. G38-G44 ◽  
Author(s):  
C. A. Flores ◽  
P. M. Brannon ◽  
M. A. Wells ◽  
M. Morrill ◽  
O. Koldovsky
Keyword(s):  
Dietary Fat ◽  
Intact Animal ◽  
Fat Intake ◽  
Fat Absorption ◽  
High Fat ◽  
High Carbohydrate ◽  
Weanling Rats ◽  
Low Carbohydrate ◽  
Triton Wr 1339

To determine the effect of altered dietary fat intake on the rate of fat absorption in the intact animal, we fed male weanling rats either a high fat-low carbohydrate (HF-LC) (calories: 67% fat, 10% carbohydrate, 20% protein) or low fat-high carbohydrate (LF-HC) (calories: 10% fat, 67% carbohydrate, 20% protein) diet for 8 days. Absorption of [14C]triolein was estimated by determining 1) 14CO2 expiration in breath, 2) intestinal triglyceride output using Triton WR-1339, an inhibitor of lipoprotein lipase, and 3) quantitating the disappearance of labeled triolein from the gastrointestinal tract. Changes in the activity of pancreatic lipase and amylase confirmed the adaptation to altered fat and carbohydrate intake. Animals fed the HF-LC diet exhibited approximately twofold greater triolein disappearance, oxidation, and intestinal triglyceride output compared with animals fed LF-HC. There was also a highly significant linear relationship between 14CO2 excretion and intestinal triglyceride output in both diet groups. These data show that high dietary fat content markedly enhances in vivo fat absorption in the weanling rat.

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.

Lymphatic chylomicron size is inversely related to biliary phospholipid secretion in mice

2006 ◽  
Vol 290 (6) ◽  
pp. G1177-G1185 ◽  
Author(s):  
Anniek Werner ◽  
Rick Havinga ◽  
Frank Perton ◽  
Folkert Kuipers ◽  
Henkjan J. Verkade
Keyword(s):  
Lipid Absorption ◽  
Fat Absorption ◽  
Very Low Density Lipoproteins ◽  
Deficient Diet ◽  
Lipoprotein Subfractions ◽  
Core Surface ◽  
Lymph Duct ◽  
The Difference ◽  
Dietary Fat Absorption ◽  
Deficient Mice

Biliary phospholipids (PL) stimulate dietary fat absorption by facilitating intraluminal lipid solubilization and by providing surface components for chylomicron (CM) assembly. Impaired hepatic PL availability induces secretion of large very-low-density lipoproteins, but it is unclear whether CM size depends on biliary PL availability. Biliary PL secretion is absent in multidrug resistance protein 2-deficient ( Mdr2−/−) mice, whereas it is strongly increased in essential fatty acid (EFA)-deficient mice. We investigated lymphatic CM size and composition in mice with absent ( Mdr2−/−) or enhanced (EFA deficient) biliary PL secretion and in their respective controls under basal conditions and during enteral lipid administration. EFA deficiency was induced by feeding mice a high-fat, EFA-deficient diet for 8 wk. Lymph was collected by mesenteric lymph duct cannulation with or without intraduodenal lipid administration. Lymph was collected in 30-min fractions for up to 4 h, and lymphatic lipoprotein size was determined by dynamic light-scattering techniques. Lymph lipoprotein subfractions were isolated by ultracentrifugation, and lipid composition was measured. Lymphatic CMs were significantly larger in Mdr2−/− mice than in Mdr2+/+ controls either without (+50%) or with (+25%) enteral lipid administration, and molar core-surface ratios were increased [triglyceride (TG)-to-PL ratio: 4.4 ± 1.4 in Mdr2−/− mice vs. 2.7 ± 0.8 in Mdr2+/+ mice, P < 0.001]. In contrast, EFA-deficient mice secreted lipoproteins into lymph that were significantly smaller than in EFA-sufficient controls (173 ± 32 vs. 236 ± 47 nm), with correspondingly decreased core-surface ratios (TG-to-PL ratio: 3.0 ± 1.0 in EFA-deficient mice vs. 6.0 ± 1.9 in EFA-sufficient mice, P < 0.001). CM size increased during fat absorption in both EFA-deficient and EFA-sufficient mice, but the difference between the groups persisted. In conclusion, the present results strongly suggest that the availability of biliary PL is a major determinant of the size of intestinally produced lipoproteins both under basal conditions and during lipid absorption. Altered CM size may have physiological consequences for postprandial CM processing.

The intestinal fatty acid binding protein is not essential for dietary fat absorption in mice

2000 ◽  
Vol 14 (13) ◽  
pp. 2040-2046 ◽  
Author(s):  
Galya Vassileva ◽  
Leslie Huwyler ◽  
Kevin Poirier ◽  
Luis B. Agellon ◽  
Matthew J. Toth
Keyword(s):  
Fatty Acid ◽  
Dietary Fat ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fat Absorption ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Dietary Fat Absorption
Sign in / Sign up

Export Citation Format

Share Document