Lack of endogenous cholecystokinin promotes cholelithogenesis in mice.

BACKGROUND: Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Cholecystokinin (CCK) release from the proximal small intestine and gallbladder emptying in response to a fatty meal are greatly reduced in celiac patients before they start the gluten-free diet, showing a genetic predisposition to gallstones. METHODS: To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous CCK on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days. KEY RESULTS: Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high-fat diet was impaired in CCK knockout (KO) mice compared to wild-type mice. Because of the absence of CCK, small intestinal transit time was prolonged and intestinal cholesterol absorption was increased. During 28 days of feeding, elevated biliary cholesterol concentrations and gallbladder stasis promoted the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. Thus, cholesterol crystallization and gallstone formation were accelerated in CCK KO mice. In contrast, daily intraperitoneal administration of CCK-8 reduced gallstone formation in CCK KO mice even on the lithogenic diet. CONCLUSIONS & INFERENCES: The lack of endogenous CCK enhances susceptibility to gallstones by impairing gallbladder contractile function and small intestinal motility function. These findings show that celiac disease is an important risk factor for gallstone formation and the gallbladder motility function should be routinely examined by ultrasonography and gallbladder stasis should be prevented in celiac patients.

Design and evaluation of a low-cost smartphone pulse oximeter.

Infectious diseases such as pneumonia take the lives of millions of children in low- and middle-income countries every year. Many of these deaths could be prevented with the availability of robust and low-cost diagnostic tools using integrated sensor technology. Pulse oximetry in particular, offers a unique non-invasive and specific test for an increase in the severity of many infectious diseases such as pneumonia. If pulse oximetry could be delivered on widely available mobile phones, it could become a compelling solution to global health challenges. Many lives could be saved if this technology was disseminated effectively in the affected regions of the world to rescue patients from the fatal consequences of these infectious diseases. We describe the implementation of such an oximeter that interfaces a conventional clinical oximeter finger sensor with a smartphone through the headset jack audio interface, and present a simulator-based systematic verification system to be used for automated validation of the sensor interface on different smartphones and media players. An excellent agreement was found between the simulator and the audio oximeter for both oxygen saturation and heart rate over a wide range of optical transmission levels on 4th and 5th generations of the iPod TouchTM and iPhoneTM devices.

With respect to elderly patients: finding kidneys in the context of new allocation concepts.

The elderly have benefited from increased access to renal transplantation in recent years. New allocation concepts would shift distribution of kidneys to younger recipients, making expanded criteria and living donor kidneys more relevant for seniors. Current issues impacting expanded criteria donor kidney availability and living donor transplant opportunities for the elderly are explored. It is hoped that the kidney donor profile index will improve risk assessment and utilization of marginal kidneys. The usefulness of procurement biopsy remains controversial. Dual kidney transplantation and machine perfusion appear to be effective mechanisms to increase organ availability. "Old-for-old" allocation systems, donation service area variation and regulatory and reimbursement issues highlight disparities and disincentives affecting expanded criteria donor organ utilization, and considerations for the way forward are discussed. Living donor transplantation, even with older donors, may provide the best option for elderly recipients, and careful expansion of the living donor pool appears appropriate. In light of new allocation concepts, it will be important to understand issues pertinent to seniors and develop effective strategies to maintain or improve their access to the benefits of transplantation.

The effect of olestra on the absorption, excretion and storage of 2,2',5,5' tetrachlorobiphenyl; 3,3',4,4' tetrachlorobiphenyl; and perfluorooctanoic acid.

Mice were gavaged with either (14)C-labeled 2,2'5,5' tetrachlorobiphenyl; 3,3',4,4' tetrachlorobiphenyl; or perfluorooctanoic acid. Absorption of these compounds was determined by assay of feces collected for 48 h after the gavage. Part of the animals received test diets containing olestra during this 48-hour period to determine its effect on absorption of the compounds. Mice that received the diet without olestra during this period were divided into groups that either continued the diet without olestra or changed to a diet containing olestra. These diets were continued for 7 days, and a second 48-hour fecal collection was made to measure the effect of olestra on enterohepatic circulation of the compounds and their metabolites. The animals were sacrificed, and blood, fat, and liver concentrations of (14)C were measured. Olestra decreased the absorption of 2,2',5,5' tetrachlorobiphenyl. It also reduced tissue and blood concentrations of this compound. Olestra also decreased the absorption of 3,3',4,4' tetrachlorobiphenyl, but it did not alter enterohepatic circulation or tissue concentrations. Olestra significantly increased the excretion of perfluorooctanoic acid in the second 48-hour collection, suggesting an effect on enterohepatic circulation. It did not, however, alter tissue concentrations of perfluorooctanoic acid. These data are consistent with previously observed effects of olestra on the absorption and storage of lipophilic compounds.

Involvement of apolipoprotein A-IV and cholecystokinin1 receptors in exogenous peptide YY3 36-induced stimulation of intestinal feedback.

Peptide YY (PYY)(3-36), released by intestinal lipid elicits functional effects that comprise the intestinal feedback response to luminal nutrients, but the pathway of action is not fully characterized. The aim of the present study was to determine the role of the apolipoprotein (apo) A-IV-cholecystokinin (CCK)(1) receptor (CCK(1)R) pathway in exogenous PYY(3-36)-induced activation of the gut-brain axis and inhibition of gastric emptying and food intake. PYY(3-36) (5 microg/100 g ip) significantly inhibited gastric emptying of a chow meal in wild-type but not A-IV(-/-) mice andCCK(1)R receptor blockade with devazepide (10 microg/100 g), abolished PYY(3-36)-induced inhibition of gastric emptying. PYY(3-36)-induced inhibition of food intake in both ad libitum-fed and 16-h fasted mice was unaltered in A-IV(-/-) mice, compared with wild-type controls, or by CCK(1)R receptor blockade with devazepide. PYY(3-36) activated neurons in the midregion of the nucleus of the solitary tract (bregma -7.32 to -7.76 mm) in A-IV(+/+) mice; this was measured by immunohistochemical localization of Fos protein. PYY(3-36)-induced Fos expression was significantly reduced by 65% in A-IV(+/+) mice pretreated systemically with the sensory neurotoxin capsaicin (5 mg/100 g), 78% by the CCK(1)R antagonist, devazepide (10 microg/100 g), and 39% by the Y2R antagonist, BIIE0246 (200 and 600 microg/100 g) and decreased by 67% in apo A-IV(-/-) mice, compared with A-IV(+/+) controls. The data suggest a role for apo A-IV and the CCK(1)R in PYY(3-36)-induced activation of the vagal afferent pathway and inhibition of gastric emptying, but this is likely not the pathway mediating the effects of PYY(3-36) on food intake.

Transplanting the highly sensitized patient: The emory algorithm.

Renal transplant patients sensitized to HLA antigens comprise nearly one-third of the UNOS wait-list and receive 14% of deceased donor (DD) transplants, a rate half that of unsensitized patients. Between 1999 and 2003, we performed 492 adult renal transplants from DD; 120 patients (approximately 25%) had a panel reactive antibody (PRA) of >30%, with nearly half (n = 58) having a PRA of >80%. Our approach is based upon high-resolution solid-phase HLA antibody analysis to identify class I/II antibodies and a 'virtual crossmatch' to predict compatible donor/recipient combinations. Recipients are excluded from the United Network for Organ Sharing match run if donors possess unacceptable antigens. Thus, when sensitized patients appear on the match run, they have a high probability of a negative final crossmatch. Here, we describe our 5-year experience with this approach. Five-year graft survival ranged from 66% to 70% among unsensitized (n = 272), moderately sensitized (PRA < 30%, n = 100) and highly sensitized (>30% PRA; n = 120) patients, equal to the average national graft survival (65.7%). The application of this approach (the Emory Algorithm) provides a logical and systematic approach to improve the access of sensitized patients to DD organs and promote more equitable allocation to a highly disadvantaged group of patients awaiting renal transplantation.

Micellar solubilisation of cholesterol is essential for absorption in humans.

BACKGROUND AND AIMS: Intralumenal bile acid (BA) concentrations have a profound effect on cholesterol absorption. We performed studies to assess the effects of markedly reduced lumenal BA on cholesterol absorption in children with inborn errors in BA synthesis and the role of micellar solubilisation of cholesterol on its absorption in an animal model using human intestinal contents. METHODS: We studied five subjects: two with 3beta hydroxy-C27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Delta(4)-3-oxosteroid 5beta reductase deficiency (5beta reductase), and one with 2-methylacyl CoA racemase deficiency (racemase). Subjects were studied on supplemental BA therapy and three weeks after withdrawal of supplements. During each treatment period a liquid meal was consumed. Duodenal samples were collected and analysed, and cholesterol absorption and cholesterol fractional synthetic rates were measured. Human intralumenal contents were infused in a bile diverted rat lymph fistula model to assess micellar versus vesicular absorption of cholesterol. RESULTS: Without BA supplementation, intralumenal BA concentrations were below the critical micellar concentration (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA supplementation. Lumenal cholesterol was carried primarily as vesicles in untreated subjects whereas it was carried as both micelles and vesicles in treated subjects. Cholesterol absorption increased approximately 55% in treated compared with untreated subjects (p=0.041), with a simultaneous 70% decrease in synthesis rates (p=0.029). In the rat lymph fistula model, minimal vesicular cholesterol was absorbed whereas vesicular and micellar fatty acid and phospholipid were comparably absorbed. CONCLUSIONS: Increasing micellar cholesterol solubilisation by supplemental BA in subjects with inborn errors of BA synthesis leads to an improvement in cholesterol absorption and reduction in cholesterol synthesis due to improved micellar solubilisation of cholesterol.

Apolipoprotein A-IV is involved in detection of lipid in the rat intestine.

Long chain triglyceride (>C12) in the intestinal lumen potently inhibits gastric emptying and acid secretion via the vagal afferent pathway. While the mechanism of inhibition involves the formation of chylomicrons, the essential role of the apolipoprotein apo A-IV is unclear. Using apo A-IV(-/-) mice, we tested the hypothesis that inhibition of gastric emptying and gastric acid secretion in response to dietary lipid is dependent upon apo A-IV. As measured by nuclear scintigraphy in awake mice, gastric emptying of an ingested whole-egg meal was significantly faster in apo A-IV(-/-) knockout versus A-IV(+/+) controls (34 +/- 1 versus 54 +/- 3 min, P < 0.0001). In anaesthetized A-IV(+/+) mice, meal-stimulated gastric acid secretion was 59% inhibited by intestinal lipid infusion; this was abolished in apo A-IV(-/-) mice. Oral gavage of lipid in awake mice activated neurones throughout the nucleus of the solitary tract (NTS) in A-IV(+/+) mice, measured by immunohistochemical localization of Fos protein expression. However, in the mid region of the NTS (bregma -7.32 to -7.76 mm), Fos expression in response to intestinal lipid was significantly decreased by 50% in apo A-IV(-/-) mice compared to A-IV(+/+) controls. We conclude that activation of the vagal afferent pathway and inhibition of gastric function in response to dietary lipid is partly dependent upon apo A-IV.

Apolipoprotein A-IV stimulates duodenal vagal afferent activity to inhibit gastric motility via a CCK1 pathway.

Apolipoprotein A-IV (apo A-IV), a peptide expressed by enterocytes in the mammalian small intestine and released in response to long-chain triglyceride absorption, may be involved in the regulation of gastric acid secretion and gastric motility. The specific aim of the present study was to determine the pathway involved in mediating inhibition of gastric motility produced by apo A-IV. Gastric motility was measured manometrically in response to injections of either recombinant purified apo A-IV (200 microg) or apo A-I, the structurally similar intestinal apolipoprotein not regulated by triglyceride absorption, close to the upper gastrointestinal tract in urethane-anesthetized rats. Injection of apo A-IV significantly inhibited gastric motility compared with apo A-I or vehicle injections. The response to exogenous apo A-IV injections was significantly reduced by 77 and 55%, respectively, in rats treated with the CCK(1) receptor blocker devazepide or after functional vagal deafferentation by perineural capsaicin treatment. In electrophysiological experiments, isolated proximal duodenal vagal afferent fibers were recorded in vitro in response to close-arterial injection of vehicle, apo A-IV (200 microg), or CCK (10 pmol). Apo A-IV stimulated the discharge of duodenal vagal afferent fibers, significantly increasing the discharge in 4/7 CCK-responsive units, and the response was abolished by CCK(1) receptor blockade with devazepide. These data suggest that apo A-IV released from the intestinal mucosa during lipid absorption stimulates the release of endogenous CCK that activates CCK(1) receptors on vagal afferent nerve terminals initiating feedback inhibition of gastric motility.

Enterocyte fatty acid uptake and intestinal fatty acid-binding protein.

This article reviews our current understanding of the uptake of fatty acids by the enterocytes of the intestine. The micellar solubilization of fatty acids by bile salts and the factors regulating that process are discussed. The mechanism of how micellar solubilization of fatty acids promotes the uptake of fatty acids by enterocytes and their relative importance is reviewed. Additionally, discussion of the various fatty acid transporters located at the brush border membrane of the enterocytes is included. Finally, a summary of our current understanding of the function of fatty-acid-binding proteins inside enterocytes is provided.

Role of extracellular signal-regulated kinases in opioid-induced adenylyl cyclase superactivation in human embryonic kidney 293 cells.

The mu-opioid receptor stimulates the activity of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in recombinant human embryonic kidney (HEK) 293 cells but this stimulatory response is abolished by prolonged opioid treatment. Chronic opioid treatment of the same cells has also been shown to induce adenylyl cyclase (AC) superactivation. This study examined the role of ERK1/2 activity in opioid-induced AC superactivation. Acute opioid treatment of HEK 293 cells expressing mu-opioid receptors resulted in the activation of ERK1/2, and this response was abolished in the presence of U0126, a MEK1/2 inhibitor. Despite a complete blockade of ERK1/2 phosphorylation, U0126 did not affect opioid-induced AC superactivation, indicating that ERK1/2 activity was not required for opioid-induced AC superactivation in HEK 293 cells.

From interaction of lipidic vehicles with intestinal epithelial cell membranes to the formation and secretion of chylomicrons.

Lipophilic drugs are carried by chylomicrons that are secreted by the small intestine and transported in lymph. This review discusses the digestion, uptake, and transport of dietary lipids and the impact that these processes have on the absorption of lipophilic drugs by the gastrointestinal tract. This chapter complements Dr. Chris Potter's chapter on the "pre-absorptive" events of drug processing and solubilization. This chapter reviews the digestion of lipids in the gastric and intestinal lumen and the role of bile salts in the solubilization of lipid digestion products for uptake by the gut. Both the passive and active uptake of lipid digestion products is discussed. How intestinal lipid transporters located at the brush border membrane may play a role in the uptake of lipids by the enterocytes is examined, as is the regulation of the absorption of cholesterol by the human ATP-binding cassette transporter-1 (ABC1). The intracellular trafficking and the resynthesis of complex lipids from lipid digestion products are explored, and the formation and secretion of chylomicrons are described.

Randomized structured triglycerides increase lymphatic absorption of tocopherol and retinol compared with the equivalent physical mixture in a rat model of fat malabsorption.

Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

An examination of the factors affecting intestinal lymphatic transport of dietary lipids.

Lipophilic drugs are carried by chylomicrons secreted by the small intestine and transported in lymph. The intent of this review is to update the reader on the digestion, uptake, and transport of dietary lipids and how these processes impact the absorption of lipophilic drugs by the gut. The digestion of lipids in the gastric and intestinal lumen is discussed as well as the role of bile salts in the solubilization of lipid digestion products for uptake by the gut. Both passive and active uptake of lipid digestion products is reviewed. Also examined is how intestinal lipid transporters located at the brush border membrane may play a role in the uptake of lipids by the enterocytes. The intracellular trafficking and the resynthesis of complex lipids from lipid digestion products are explored. Finally, the formation and secretion of chylomicrons and their potential clinical disorders are described.

Effect of leptin on intestinal apolipoprotein AIV in response to lipid feeding.

We determined apolipoprotein AIV (apo AIV) content in intestinal epithelial cells using immunohistochemistry when leptin was administered intravenously. Most of the apo AIV immunoreactivity in the untreated intestine was located in the villous cells as opposed to the crypt cells. Regional distribution of apo AIV immunostaining revealed low apo AIV content in the duodenum and high content in the jejunum that gradually decreases caudally toward the ileum. Intraduodenal infusion of lipid (4 h) significantly increased apo AIV immunoreactivity in the jejunum and ileum. Simultaneous intravenous leptin infusion plus duodenal lipid infusion markedly suppressed apo AIV immunoreactivity. Duodenal lipid infusion increased plasma apo AIV significantly (measured by ELISA), whereas simultaneous leptin infusion attenuated the increase. These findings suggest that leptin may regulate circulating apo AIV by suppressing apo AIV synthesis in the small intestine.

The role of apolipoprotein A-IV in the regulation of food intake.

Apolipoprotein A-IV (apo A-IV) is a glycoprotein synthesized by the human intestine. In rodents, both the small intestine and liver secrete apo A-IV, but the small intestine is the major organ responsible for the circulating apo A-IV. Intestinal apo A-IV synthesis is markedly stimulated by fat absorption and appears not to be mediated by the uptake or reesterification of fatty acids to form triglycerides. Rather, the formation of chylomicrons acts as a signal for the induction of intestinal apo A-IV synthesis. Intestinal apo A-IV synthesis is also enhanced by a factor from the ileum, probably peptide tyrosine-tyrosine. The inhibition of food intake by apo A-IV is mediated centrally. The stimulation of intestinal synthesis and the secretion of apo A-IV by lipid absorption are rapid; thus, apo A-IV likely plays a role in the short-term regulation of food intake. Other evidence suggests that apo A-IV may also be involved in the long-term regulation of food intake and body weight. Chronic ingestion of a high-fat diet blunts the intestinal apo A-IV response to lipid feeding and may explain why the chronic ingestion of a high-fat diet predisposes both animals and humans to obesity.

Epithelial permeability is not increased in rats following small bowel resection.

BACKGROUND: Increased intestinal permeability and translocation of bacteria and/or bacterial products may cause infection and liver dysfunction in patients with the short bowel syndrome. In previous studies, serum from mice undergoing small bowel resection (SBR) enhanced growth of cultured rat intestinal epithelial cells (RIEC-6), implicating a role for a serum factor(s) in the enterocyte response to SBR. These experiments tested the hypothesis that epithelial cell permeability is increased following SBR. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent a 75% SBR or sham operation. Intestinal permeability in the remnant ileum was determined by Ussing chambers on Postoperative Day (POD) 3. Additionally, serum was collected on POD 1, 3, and 7 and mesenteric lymph was harvested on POD 3. Once confluent, RIEC-6 cells were incubated for 3 days in media supplemented with 10% fetal bovine serum (FBS; control), 1% FBS, 1% FBS plus 9% Sham serum, or 1% FBS plus 9% SBR serum or exposed to media with varied concentrations of SBR or Sham lymph. Monolayer permeability was determined by measuring the passage of dextran-rhodamine. RESULTS: Intestinal permeability was reduced in rats undergoing SBR. Sham serum-treated monolayers demonstrated the greatest permeability. Incubation with SBR serum reduced permeability to near control media. There were no permeability differences between SBR and Sham lymph-treated monolayers. CONCLUSION: The early adaptive response of the remnant intestine after SBR is associated with reduced permeability. These results suggest an alternative mechanism for the increased bacterial translocation that has been described following SBR.

Intestinal satiety protein apolipoprotein AIV is synthesized and regulated in rat hypothalamus.

Apolipoprotein AIV (apo AIV) is a satiety protein secreted by the small intestine. We demonstrate for the first time that apo AIV protein and apo AIV mRNA are present in rat hypothalamus, a site intimately involved in the integration of signals for regulation of food intake and energy metabolism. We further characterized the regulation of hypothalamic apo AIV mRNA levels. Food-deprived animals showed a pronounced decrease in gene expression of apo AIV in the hypothalamus, with a concomitant decrease in the jejunum. Refeeding fasted rats with standard laboratory chow for 4 h evokes a significant increase of apo AIV mRNA in jejunum but not in hypothalamus. However, lipid refeeding to the fasted animals restored apo AIV mRNA levels both in hypothalamus and jejunum. Intracerebroventricular administration of apo AIV antiserum not only stimulated feeding, but also decreased apo AIV mRNA level in the hypothalamus. These data further confirm the central role of apo AIV in the regulation of food intake.

Compensatory phospholipid digestion is required for cholesterol absorption in pancreatic phospholipase A(2)-deficient mice.

BACKGROUND AND AIMS: Numerous studies have suggested phospholipid inhibition of dietary cholesterol absorption through the gastrointestinal tract. This study addressed the importance of luminal phospholipid hydrolysis in this process. METHODS: The effect of phospholipase inhibition on cholesterol transport from intestinal lumen to the lymphatics was evaluated in lymph fistula rats. Cholesterol and phospholipid absorption efficiency in intact animals was evaluated in control and phospholipase A(2) (PLA2) gene-targeted mice. RESULTS: The PLA2 inhibitor FPL 67047XX retarded cholesterol absorption in a lymph fistula rat model. Under basal chow-fed dietary conditions, cholesterol absorption efficiency from a single bolus meal, and plasma lipid levels, were similar among PLA2+/+, PLA2+/-, and PLA2-/- mice. Interestingly, the nonhydrolyzable phospholipid dioleoyl ether phosphatidylcholine suppressed cholesterol absorption by 10% to 18% in mice without regard to their PLA2 genotype. When 1-palmitoyl-2-[(14)C]oleoyl-phosphatidylcholine was used as the substrate, the radiolabeled phospholipid was found to be hydrolyzed and absorbed with equal efficiency in PLA2+/+, PLA2+/-, and PLA2-/- mice. CONCLUSIONS: These results suggested that although phospholipid digestion in the intestinal lumen is a prerequisite for efficient cholesterol absorption, additional enzyme(s) can compensate for pancreatic PLA2 in catalyzing phospholipid digestion and facilitating cholesterol absorption in PLA2 knockout mice.

Intestinal lipid absorption and transport.

The purpose of this review is to update the reader on our current knowledge of the digestion, uptake, and transport of dietary lipid. In particular, it discusses how intestinal lipid transporters may play a role in the uptake of lipids by the enterocytes, and how chylomicrons are formed in the enterocytes and packaged for export into the lymphatic system through exocytosis. The classification and properties of lipids is first described followed by a discussion of structured lipids and their role in human nutrition. Digestion of triacylglycerols takes place in the stomach aided by the enzyme gastric lipase. The origin and properties of lingual and gastric lipase are reviewed. Most digestion of triacylglycerols by pancreatic lipase occurs in the intestinal lumen. Similarly, digestion of cholesteryl ester and phospholipids also takes place in the intestinal lumen. This review describes in considerable detail the uptake of lipid digestion products by the enterocytes, particularly the role of recently identified lipid transporters. The intracellular trafficking and the resynthesis of complex lipids from the lipid digestion products are talked about, particularly within the context of the recently generated knockout mouse that lacks the key lipid reesterification enzymes. Finally, the mechanisms of the formation and secretion of chylomicrons is described and clinical disorders discussed.