Triacylglycerol Absorption Research Articles

Garcinia mangostana Suppresses Triacylglycerol Synthesis in Hepatocytes and Enterocytes.

Regulation of diacylglycerol acyltransferase (DGAT) and pancreatic lipase (PL) activities is important in the treatment of triacylglycerol (TG)-related metabolic diseases. Garcinia mangostana, also known as mangosteen, is a traditional medicine ingredient used in the treatment of inflammation in Southeast Asia. In this study, The ethanolic extract of G. mangostana peel inhibited human recombinant DGAT1 and DGAT2, and PL enzyme activities in vitro. The inhibitory activity of DGAT1 and DGAT2 enzymes of four representative bioactive substances in mangosteen was confirmed. In addition, G. mangostana was confirmed to suppress the serum TG levels in C57 mice by inhibiting the absorption and synthesis of TG in the gastrointestinal tract. Through this study, it was revealed that G. mangostana extract could be useful for the prevention and amelioration of TG-related metabolic diseases such as obesity and fatty liver.

Mechanisms of intestinal triacylglycerol synthesis

Triacylglycerols are a major source of stored energy that are obtained either from the diet or can be synthesized to some extent by most tissues. Alterations in pathways of triacylglycerol metabolism can result in their excessive accumulation leading to obesity, insulin resistance, cardiovascular disease and nonalcoholic fatty liver disease. Most tissues in mammals synthesize triacylglycerols via the glycerol 3-phosphate pathway. However, in the small intestine the monoacylglycerol acyltransferase pathway is the predominant pathway for triacylglycerol biosynthesis where it participates in the absorption of dietary triacylglycerol. In this review, the enzymes that are part of both the glycerol 3-phosphate and monoacylglycerol acyltransferase pathways and their contributions to intestinal triacylglycerol metabolism are reviewed. The potential of some of the enzymes involved in triacylglycerol synthesis in the small intestine as possible therapeutic targets for treating metabolic disorders associated with elevated triacylglycerol is briefly discussed.

Dairy-Derived Emulsifiers in Infant Formula Show Marginal Effects on the Plasma Lipid Profile and Brain Structure in Preterm Piglets Relative to Soy Lecithin.

Breastfed infants have higher intestinal lipid absorption and neurodevelopmental outcomes compared to formula-fed infants, which may relate to a different surface layer structure of fat globules in infant formula. This study investigated if dairy-derived emulsifiers increased lipid absorption and neurodevelopment relative to soy lecithin in newborn preterm piglets. Piglets received a formula diet containing soy lecithin (SL) or whey protein concentrate enriched in extracellular vesicles (WPC-A-EV) or phospholipids (WPC-PL) for 19 days. Both WPC-A-EV and WPC-PL emulsions, but not the intact diets, increased in vitro lipolysis compared to SL. The main differences of plasma lipidomics analysis were increased levels of some sphingolipids, and lipid molecules with odd-chain (17:1, 19:1, 19:3) as well as mono- and polyunsaturated fatty acyl chains (16:1, 20:1, 20:3) in the WPC-A-EV and WPC-PL groups and increased 18:2 fatty acyls in the SL group. Indirect monitoring of intestinal triacylglycerol absorption showed no differences between groups. Diffusor tensor imaging measurements of mean diffusivity in the hippocampus were lower for WPC-A-EV and WPC-PL groups compared to SL indicating improved hippocampal maturation. No differences in hippocampal lipid composition or short-term memory were observed between groups. In conclusion, emulsification of fat globules in infant formula with dairy-derived emulsifiers altered the plasma lipid profile and hippocampal tissue diffusivity but had limited effects on other absorptive and learning abilities relative to SL in preterm piglets.

Do Flavonoids from Durum Wheat Contribute to Its Bioactive Properties? A Prospective Study.

A clear gap with respect to the potential biological properties of wheat flavonoids exists in the available literature. This information is crucial for breeding programs aiming to produce new varieties presenting improved health benefits. Accordingly, advanced breeding lines of whole durum wheat were evaluated in this contribution. The highest recovery of phenolics was achieved using aqueous acetone (50:50, v/v), as verified by multi-response optimization, thus showing that phenolics could be largely underestimated by employing an inappropriate extraction. The concentration of derivatives of apigenin, the main phenolics present, ranged from 63.5 to 80.7%, as evaluated by LC–ESI-QTOF-MS. Phenolics from the breeding line 98 exhibited the highest ability in scavenging peroxyl radicals, reducing power as well as in terms of inhibition of pancreatic lipase activity, a key enzyme regulating the absorption of triacylglycerols. In contrast, none of the samples exhibited a significant anti-diabetic potential. Despite their high concentration compared to that of phenolic acids, results of this work do not support a significant antioxidant and pancreatic lipase inhibitory effect of durum wheat flavonoids. Therefore, breeding programs and animal and/or human trials related to the effect of durum wheat flavonoids on oxidative stress and absorption of triacylglycerols are discouraged at this point.

Post-oral fat-induced satiation is mediated by endogenous CCK and GLP-1 in a fat self-administration mouse model

Triacylglycerol is the most abundant dietary lipid, and a strong stimulator of satiation. Absorption of triacylglycerol in the small intestine occurs in the form of free fatty acids and 2-monoacylglycerol, a process known to trigger not only the release of cholecystokinin (CCK) but also glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). It remains controversial, however, whether endogenously released GLP-1 and PYY are required for fat-induced satiation. Using a self-administration model where mice are trained to self-administer Intralipid 30% intragastrically, we show that blocking the CCK1 receptors with intraperitoneal devazepide diminishes the post-oral satiation effect of ingested fat. Similarly, s.c. administration of a GLP-1 receptor antagonist with a prolonged half-life (Jant4-C16) also reduced the post-oral satiation effect of ingested fat. Importantly, coadministration of the GLP-1 antagonist together with devazepide increased fat self-infusions to a level equal to the combined blockade of each individual peptide action alone, indicating an additive effect of endogenous CCK and GLP-1 in fat satiation signaling. Blocking the PYY Y2 receptor did not further enhance the fat intake in devazepide-treated mice. Consistent with the above, we show that voluntary post-oral ingestion of fat increases CCK and GLP-1 plasma levels and is correlated positively with CCK and GLP-1 plasma concentrations. Taken together, our results support the role of endogenous GLP-1 in the regulation of fat intake and suggest that both CCK and GLP-1 are required for the fat satiation signaling.

Modulation of Lipid Transport and Adipose Tissue Deposition by Small Lipophilic Compounds.

Small lipophilic molecules present in foods of plant origin have relevant biological activities at rather low concentrations. Evidence suggests that phytosterols, carotenoids, terpenoids, and tocopherols can interact with different metabolic pathways, exerting beneficial effects against a number of metabolic diseases. These small molecules can modulate triacylglycerol absorption in the intestine and the biosynthesis of chylomicrons, the lipid carriers in the blood. Once in the bloodstream, they can impact lipoprotein clearance from blood, thereby affecting fatty acid release, incorporation into adipocytes and triglyceride reassembling and deposit. Consequently, some of these molecules can regulate pathophysiological processes associated to obesity and its related conditions, such as insulin resistance, metabolic syndrome and type-2 diabetes. The protective capacity of some lipophilic small molecules on oxidative and chemotoxic stress, can modify the expression of key genes in the adaptive cellular response, such as transcription factors, contributing to prevent the inflammatory status of adipose tissue. These small lipophilic compounds can be incorporated into diet as natural parts of food but they can also be employed to supplement other dietary and pharmacologic products as nutraceuticals, exerting protective effects against the development of metabolic diseases in which inflammation is involved. The aim of this review is to summarize the current knowledge of the influence of dietary lipophilic small biomolecules (phytosterols, carotenoids, tocopherols, and triterpenes) on lipid transport, as well as on the effects they may have on pathophysiological metabolic states, related to obesity, insulin resistance and inflammation, providing an evidence-based summary of their main beneficial effects on human health.

Addition of high load of lysophosphatidic acid to standard and high-fat chows causes no significant changes of its circulating and peripheral tissue levels but affects body weight and visceral fat mass of mice.

Oral administration of lysophosphatidic acid (LPA), a critical intercellular lipid mediator, exerts wound healing and antiulcer effects on gastrointestinal system. To evaluate effects of food-derived LPA on body homeostasis, we measured LPA levels by liquid chromatography-tandem mass spectrometry in chows, feces, plasma, liver, and visceral fat of mice fed a normal or high-fat chow supplemented with or without LPA-rich soybean phospholipids for 30 days. Reductions in daily body weight gains and visceral fat mass were mainly related to lower chow intake by mice fed the LPA-rich high-fat chow, whereas reduced body weight gains and fat mass were mainly related to decreased intestinal triacylglycerol absorption in mice fed LPA-rich chow. Our results showed no significant increase in plasma, liver, or adipose LPA levels, even if a quite high LPA concentration (2.0%) in chows was ingested daily, suggesting limited effects of food-derived LPA on the lumen side of the digestive tract. © 2018 BioFactors, 44(6):548-557, 2018.

Phenolic Profile of Peanut By‐products: Antioxidant Potential and Inhibition of Alpha‐Glucosidase and Lipase Activities

AbstractFree, esterified, etherified and insoluble‐bound phenolics from three samples, namely meal from whole peanuts (MWP), meal from dry‐blanched peanuts (MDBP) and peanut skin (PS) were evaluated for their total phenolic content (TPC), and phenolic profile using HPLC–DAD–ESI–MSn. The TPC was in the order of PS > MWP > MDBP. Among 37 compounds identified 10 were reported for peanuts for the first time. Proanthocyanidins were detected in peanut skin and MWP, but not in MDBP. The presence of peanut skin in MWP rendered up to 9.8‐fold higher scavenging activity towards the DPPH radical as compared with MDBP. Phenolics from all samples and fractions showed inhibition of alpha‐glucosidase and lipase activities, which are key enzymes involved in the absorption of glucose and triacylglycerols, respectively. Therefore, their antioxidant properties as well as their potential role in the management of diabetes and obesity makes them worthy of further consideration as functional food ingredients.

Su2089 - Hepatocyte PPARγ May Regulate Intestinal Absorption and/or Hepatic Clearance of Triacylglycerols, to Prevent Postprandial Dyslipidemia

Su2089 - Hepatocyte PPARγ May Regulate Intestinal Absorption and/or Hepatic Clearance of Triacylglycerols, to Prevent Postprandial Dyslipidemia

An LC-MRM method for measuring intestinal triglyceride assembly using an oral stable isotope-labeled fat challenge.

A traditional oral fatty acid challenge assesses absorption of triacylglycerol (TG) into the periphery through the intestines, but cannot distinguish the composition or source of fatty acid in the TG. Stable isotope-labeled tracers combined with LC-MRM can be used to identify and distinguish TG synthesized with dietary and stored fatty acids. Concentrations of three abundant TGs (52:2, 54:3 and 54:4) were monitored for incorporation of one or two (2)H11-oleate molecules per TG. This method was subjected to routine assay validation and meets typical requirements for an assay to be used to support clinical studies. Calculations for the fractional appearance rate of TG in plasma are presented along with the intracellular enterocyte precursor pool for 12 study participants.

ABCG5/G8 deficiency in mice reduces dietary triacylglycerol and cholesterol transport into the lymph.

The adenosine triphosphate-binding cassette (ABC) transporter G5/G8 is critical in protecting the body from accumulating dietary plant sterols. Expressed in the liver and small intestine, it transports plant sterols into the biliary and intestinal lumens, thus promoting their excretion. The extent to which G5/G8 regulates cholesterol absorption remains unclear. G5/G8 is also implicated in reducing the absorption of dietary triacylglycerols (TAG) by unknown mechanisms. We hypothesized that G5/G8 suppresses the production of chylomicrons, and its deficiency would enhance the absorption of both dietary TAG and cholesterol. The aim of this study was to investigate the effects of G5/G8 deficiency on lipid uptake and secretion into the lymph under steady-state conditions. Surprisingly, compared with wild-type mice (WT) (n=9), G5/G8 KO (n=13) lymph fistula mice given a continuous intraduodenal infusion of [3H]-TAG and [14C]-cholesterol showed a significant (P<0.05) reduction in lymphatic transport of both [(3)H]-TAG and [(14)C]-cholesterol, concomitant with a significant (P<0.05) increase of [(3)H]-TAG and [(14)C]-cholesterol accumulated in the intestinal lumen. There was no difference in the total amount of radiolabeled lipids retained in the intestinal mucosa between the two groups. G5/G8 KO mice given a bolus of TAG showed reduced intestinal TAG secretion compared with WT, suggesting an independent role for G5/G8 in facilitating intestinal TAG transport. Our data demonstrate that G5/G8 deficiency reduces the uptake and secretion of both dietary TAG and cholesterol by the intestine, suggesting a novel role for the sterol transporter in the formation and secretion of chylomicrons.

Effects of Heat-KilledLactobacillus pentosusS-PT84 on Postprandial Hypertriacylglycerolemia in Rats

The effect of Lactobacillus pentosus strain S-PT84 (S-PT84) on postprandial hypertriacylglycerolemia was investigated in rats. S-PT84 dose-dependently inhibited the hydrolysis of triacylglycerols by pancreatic lipase in vitro. Intragastric administration of S-PT84 significantly reduced the lymphatic recovery of (3)H-trioleoylglycerol up to 8 h. The oral administration of a fat emulsion, with or without S-PT84, resulted in the concentration of plasma triacylglycerol 2 h and 3 h after administration being significantly lower in the S-PT84 group than in the group without S-PT84 (control group). These results suggest that S-PT84 alleviated postprandial hypertriacylglycerolemia by delaying triacylglycerol absorption in the intestine through the inhibition of pancreatic lipase.

Sesamol Treatment Reduces Plasma Cholesterol and Triacylglycerol Levels in Mouse Models of Acute and Chronic Hyperlipidemia

The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200mg/kg) significantly (P<0.05) decreased triacylglycerol absorption in the fat tolerance test by showing a dose-dependent decrease in triacylglycerol levels. The hypolipidemic effect of sesamol at 200mg/kg was equivalent to 10mg/kg of orlistat. In the tyloxapol-induced hyperlipidemia model, Sesamol at 200mg/kg reversed the elevated levels of cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2% w/w), cholic acid (1% w/w) and coconut oil 30% (v/w) with standard powdered standard animal chow (up to 100g). Niacin (100mg/kg) and sesamol (100mg/kg) significantly (P<0.05) reduced the elevated body weight compared with the high fat diet control group. Elevated levels of cholesterol and triacylglycerol were significantly (P<0.05) reversed by the sesamol (50 and 100mg/kg), implying that it might reduce the absorption and increase the excretion of cholesterol as well.

Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice

Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid.

Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine

Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats

BackgroundDietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats.MethodsIn Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3.ResultsNo observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration.ConclusionsThese results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.

Black-Tea Polyphenols Suppress Postprandial Hypertriacylglycerolemia by Suppressing Lymphatic Transport of Dietary Fat in Rats

Administration of black-tea polyphenols (BTP) at 100 and 200 mg/kg of body weight in rats suppressed postprandial hypertriacylglycerolemia in a dose-dependent manner. Administration of BTP also suppressed lymphatic recovery of (14)C-trioleoylglycerol in rats that were cannulated in the thoracic duct. BTP dose-dependently inhibited the activity of pancreatic lipase in vitro with an IC50 of 0.254 mg/mL. When purified theaflavins, which are components of BTP, were used, theaflavins with galloyl moieties, but not those without galloyl moiety, inhibited the activity of pancreatic lipase. Theaflavin-3,3'-digallate (TFDG) was more effective in inhibiting the activity of pancreatic lipase than epigallocatechin gallate (EGCG), epicatechin gallate (ECG), and a mixture of EGCG and ECG. BTP and TFDG had a similar effect in inhibiting the activity of pancreatic lipase when the total polyphenol amount was adjusted to the same. BTP had no effect on micellar solubility of hydrolysis products of triacylglycerol. These results suggest that BTP suppressed postprandial hypertriacylglycerolemia by reducing triacylglycerol absorption via the inhibition of pancreatic lipase activity.

Multifunctional effects of green tea catechins on prevention of the metabolic syndrome.

Tea catechins reduce serum cholesterol concentrations and suppress postprandial hypertriacylglycerolemia in experimental animals and humans. These effects are mainly ascribed to the gallate esters of catechins, (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG). During pasteurization of tea drinks, tea catechins are epimerized to so-called heat-treated tea catechins such as (-)-catechin gallate (CG) and (-)-gallocatechin gallate (GCG). We showed that both tea catechins and heat-treated tea catechins with the galloyl moiety lowered intestinal absorption of cholesterol by inhibiting micellar solubility of cholesterol. Since they inhibited pancreatic lipase in vitro and slowed down lymphatic absorption of triacylglycerols, it is suggested that delayed intestinal absorption of triacylglycerols after the feeding of catechin preparations causes suppression of postprandial hypertriacylglycerolemia. It has been reported that tea catechins and heat-treated tea catechins with the galloyl moiety suppress deposition of visceral fat in experimental animals and humans. Some studies suggest that the stimulation of hepatic beta-oxidation might be a cause for reduced deposition of visceral fat. However, our study did not show any acceleration of beta-oxidation in rat livers. Although there are some controversial observations, results obtained suggest a possibility that tea catechins and heat-treated tea catechins with the galloyl moiety improve lipid metabolism and contribute to the prevention of the metabolic syndrome.

Pre-hydrolysis improves absorption of neutral lipids in Atlantic halibut (Hippoglossus hippoglossus, L.) larvae

To investigate if digestion is limiting for absorption of dietary neutral lipids in Atlantic halibut (Hippoglossus hippoglossus, L.) larvae, absorption of triacylglycerol (TAG), diacylglycerol, (DAG), and monoacylglycerol, (MAG) as well as phosphatidylcholine (PC) was studied by tube-feeding larvae with radio-labelled lipids and tracing the radioactivity. PC was included to evaluate any difference in absorption of neutral versus polar lipids. The labelled lipids where deposited by tube-feeding before larvae were incubated individually for 18 h with collection of expired CO2. At sampling, the gut was separated from the body carcass and radioactivity traced in four different compartments, namely body carcass, gut, incubation water and CO2 expired from larvae. The relative (%) isotope distribution of each compartment was calculated and the dose size effect analysed by regression analysis.The results show that there is an increasing amount of evacuated unabsorbed neutral lipids as the complexity of the lipid increases (TAG>DAG>MAG). The larval faecal evacuation ranged from 66±20% of TAG to 9±6% of MAG. DAG was intermediate with 52±21% evacuated. Of the labelled PC, 37±16% was absorbed, but this can not be directly compared to the neutral lipids due to the different digestive enzymes that specifically hydrolyse neutral and polar lipids. Increasing the administered amount of lipids only slightly increased the total amount of labelled TAG and DAG that were actually absorbed, while there was a linear correlation between fed and absorbed MAG. The absorption of PC was also linearly related to the administered amount. The difference in net absorption of labelled TAG, DAG and MAG diets indicates that digestion is a limiting factor for absorption of neutral lipids in Atlantic halibut larvae.

Carboxyl Ester Lipase Deficiency Exacerbates Dietary Lipid Absorption Abnormalities and Resistance to Diet-induced Obesity in Pancreatic Triglyceride Lipase Knockout Mice

This study evaluated the contributions of carboxyl ester lipase (CEL) and pancreatic triglyceride lipase (PTL) in lipid nutrient absorption. Results showed PTL deficiency has minimal effect on triacylglycerol (TAG) absorption under low fat dietary conditions. Interestingly, PTL(-)(/)(-) mice displayed significantly reduced TAG absorption compared with wild type mice under high fat/high cholesterol dietary conditions (80.1 +/- 3.7 versus 91.5 +/- 0.7%, p < 0.05). Net TAG absorption was reduced further to 61.1 +/- 3.8% in mice lacking both PTL and CEL. Cholesterol absorption was 41% lower in PTL(-/-) mice compared with control mice (p < 0.05), but this difference was not exaggerated in PTL(-/-), CEL(-/-) mice. Retinyl palmitate absorption was reduced by 45 and 60% in PTL(-/-) mice (p < 0.05) and PTL(-/-), CEL(-/-) mice (p < 0.01), respectively. After 15 weeks of feeding, the high fat/high cholesterol diet, wild type, and CEL(-/-) mice gained approximately 24 g of body weight. However, body weight gain was 6.2 and 8.6 g less (p < 0.01) in PTL(-/-) and PTL(-/-), CEL(-/-) mice, respectively, despite their consumption of comparable amounts of the high fat/high cholesterol diet. The decrease body weight gain in PTL(-/-) and PTL(-/-), CEL(-/-) mice was attributed to their absorption of fewer calories from the high fat/high cholesterol diet, thereby resulting in less fat mass accumulation than that observed in wild type and CEL(-/-) mice. Thus, this study documents that PTL and CEL serve complementary functions, working together to mediate the absorption of a major portion of dietary fat and fat-soluble vitamin esters. The reduced lipid absorption efficiency due to PTL and CEL inactivation also resulted in protection against diet-induced obesity.