Lipid Absorption And Transport In Ruminants
Lipid Absorption and Transport in RuminantsD. BAUCHARTEquipe de Recherches MBtaboiisrnes Energetique et LipidiqueLaboratoire Croissance et Metabolisrnes des Herbivoreslnstitut National de la Recherche AgronomiqueCentre de Recherches de Clermont-Ferrand-Theix63122 Saint-Genes-Champanelle, FranceABSTRACTYThe objective of this paper is to review new insights on the biologicalmechanisms of absorption and transportof lipid in ruminants, especially the modem concepts and analytical methods usedin studies on structural properties andintravascular and tissue metabolism oflipoproteins and their factors of variation. The intestinal absorption of lipids(including long-chain fatty acids) isdetailed, and variations in the qualitativeand the quantitative aspects of absorptionwith diet composition, especially forhigh fat diets, are presented. Also, structural properties and distribution characteristics of lipoprotein classes in differentlymphatic and blood vessels are compared across several animal species.Physicochemical and hydrodynamicproperties of the lipoprotein particles andtheir apolipoprotein moieties are givenfor the main classes of lipoproteins. Finally, lipoprotein metabolism is discussed in relation to development andphysiological, nutritional, and hormonalstatus. Intravascular metabolism of lipoproteins, including the role of lipolyticenzymes and lipid transfer proteins, ispresented. Characteristics of the intestinal and hepatic synthesis of lipoproteinsand apolipoprotein fractions are compared, especially through experimentsstimulating the hepatic secretion oftriglyceride-rich lipoproteins. Differentmethods of measurement of lipoproteintissue uptake or secretion in ruminantsare discussed.(Key words: lipids, intestinal absorption,Received June 23, 1992.Accepted November 13, 1992.1993 J Dairy Sci 76:3864-3881lipoprotein metabolism, nutritional andphysiological status)Abbreviation key: ACAT acy1:cholesterolacyltransferase, apo apolipoprotein (usedwith A, B, C, D, and E), CE cholesterylesters, FA fatty acids, HDL high densitylipoproteins, IDL intermediate densitylipoproteins, LCAT 1ecithin:cholesterolacyltransferase, LDL low density lipoproteins, LPL lipoprotein lipase, M, molecular weight, PC phosphatidylcholine,PL phospholipids, TG triglycerides,VLDL very low density lipoproteins.DIGESTION AND ABSORPTION OF LIPIDSIN THE SMALL INTESTINEComposition of Lipids Entering the DuodenumIn adult ruminants, lipid digestion begins inthe enlarged forestomach (reticulorumen), but,in nonruminants, little digestion occurs beforelipids enter the small intestine. The initialstages of ruminant digestion are characterizedby intense lipolysis, fatty acid (FA) hydrogenation, and de novo lipid cellular synthesis bymicroorganisms [see the review by Jenkins(63)]. Very little absorption of the waterinsoluble long-chain FA takes place in theforestomach and the abomasum (89).Thus, lipids of postruminal digesta aremainly composed of saturated NEFA (fromdietary and microbial origin; 70%) and smalland variable amounts of microbial phospholipids (PL) (10 to 20%); all are adsorbedpredominantly on particulate matter (75, 87,89). Similarly, triglycerides (TG) of protectedfat diets also may be present in the postruminaldigesta, associated with solid material. In theparticularly acid conditions of abomasal andduodenal digesta @H 2.0 to 2.5), NEFA arefully protonated (no ionic form is present),which maintains lipid absorption onto the surface of particulate matter (89).3864
SYMPOSIUM: RUMINANT LIPID METABOLISMLipid Digestion in the Small IntestineLipid digestion occurs in a biphasicmedium that consists of an insoluble particulate phase to which free FA (and PL) areattached and a soluble micellar phase containing dissolved FA. Transfer of free FA to themicellar phase occurs gradually as digesta gothrough the intestinal tract; 5% of the totaltransfer occurs in the duodenum, 20% in theupper jejunum, 25% in the mid and lowerjejunum, and 50% in the ileum (75). The process by which FA are released from particulatematter involves polar detergency. Bile secretion in the duodenum favors the interaction ofFA with bile PL and water which leads to theformation of a liquid crystalline phase. Withincreasing pH, this phase then is dispersed inthe presence of bile salts to form the micellarsolution. Conversion of bile PL tolysophospholipids by pancreatic phospholipaseA2 stimulated micellar solubilization of FA (aspossibly did PL) and thus improved the FApassage through the unstirred water layer adjacent to the microvilli of the small intestine andthe subsequent absorption by the intestinalmucosal cells (78).With conventional diets, 15 to 25% of totalFA are absorbed readily in the upper jejunum(pH2.8 to 4.2); 55 to 65% of digesta FA areabsorbed in the middle and the lower jejunum@H 4.2 to 7.6) (75, 87, 89).With diets containing protected lipids, lipiddigestion by ruminants occurs, as it does inmonogastric animals, in a biphasic system consisting of an oil phase and a micellar phase.Pancreatic lipase and colipase systems convertTG into free FA and 2-monoacylglycerols,which constitute an important factor in themicellar solubilization of free FA (87). Underthose dietary conditions and because of theoptimal pH @H 7.5) of lipase activity, TGhydrolysis and, thus, FA absorption do nottake place before the midjejunum (75).Quantitative Aspects of IntestinalLipid AbsorptionUsing a wide variety of techniques, such asFA flow measurements in the digestive tract ofduodenally cannulated ruminants, numerousauthors demonstrated the higher efficiency ofruminants to absorb FA compared with nonruminants (8,24,49, 58, 59,75, 87, 88, 89,98,120).3865Generally, the intestinal absorption coeffcient of individual FA ranges from 80% (forsaturated FA) to 92% (for polyunsaturated FA)in conventional diets with low fat content (2 to3% DM). The particularly high efficiency ofruminants to absorb saturated FA can be explained by two factors: 1) the great capacity ofthe bile salt and lysophospholipid micellar system to solubilize FA and 2) the acid conditions(pH 3.0 to 6.0) of duodenal and jejunal contents. This low pH is due to a low concentration of pancreatic bicarbonate (73, whichprobably limits strongly the formation of insoluble Ca soaps with saturated FA.Use of fat-supplemented diets has been developed during the past decade to meet theenergy needs of high yielding dairy cows innegative energy balance (98). Fat addition increases energy density of diets and, thus, allows maximal fat intake but may alter rumenmicrobial metabolism. Consequently, numerous products have been tested and comparedfor rumen inertness and digestibility (8,49, 64,88, 97, 120, 131).Increasing the dietary fats generally resultsin higher apparent intestinal FA digestibilitybecause of dilution of bile FA and of bacterialFA produced in the large intestine. True FAdigestibility of dauy cows seems to decreaseprogressively from 95 to 78% when FA intakeincreases from 200 g/d (1% DM) to 1400 g/d(8% DM) (97).This decrease suggests limitedsecretion and activity of pancreatic lipase andbiliary lipids (bile salts, PL), which may affectlipid absorption in ruminants at high fat intakes. The role of PL in micelle formation isgreater in ruminants than in monogastrics because of the absence of 2-monoglycerides.However, in the case of oil infusion in theproximal duodenum of dairy caws in earlylactation, similar FA digestibilities (75 to 78%)were calculated with high amounts of FA infused (1250 to 1700 gld) with or without addition of lecithin in the diet (24).The intestinal digestibility of FA may beaffected by the source and type of presentationof dietary fats. The FA digestibility was lowerin dairy cows fed diets containing 1 to 2 kg offull fat crushed rapeseed (76.4 and 84.2 vs91.4%) (88). Among other hypotheses, alimited capacity of FA digestion relative to FAintake has been suggested (88). Moreover, incomplete availability of FA when associatedwith the cellular structure of feeds for micelleformation also could be considered.Journal of Dairy Science Vol. 76, No. 12, 1993
3866BAUCHARTDigestibility of total or individual FA washigher in dairy cows fed diets containing Casoaps of palm FA compared with diets containing animal-vegetable blend fat (3 and 6%of DM) (131). These results could be explainedby the higher proportion of unsaturated FA induodenal digesta with the Ca soap diets. Indeed, Ca soaps are very stable in rumen contents and could provide more effective protection against rumen biohydrogenation. However, compared with a low fat control diet,these high fat diets lowered intestinal digestibility, which emphasizes difficulties in micellar solubilization and absorption processes ofFA in these cows. By contrast, intestinal digestibility of total FA in cows fed a dietcontaining emulsified fat (from milk; 10%DM) was higher (86 vs 80%) than with the lowfat control diet (8).LIPID TRANSPORT SYSTEM IN RUMINANTSThe main function of plasma lipoproteins isto transport lipids from secreting organs (intestine and liver) to peripheral tissues. In farmanimals, especially ruminants, the chemicalcomposition and the rate of secretion oflipoproteins are among the main factors thatcontrol lipid utilization by tissues and, thereby,the qualitative and quantitative characteristicsof meat production and milk yield. Research inthis area in the last two decades has improvedknowledge of the influence of lipoproteins inthe partition of lipids among skeletal muscles,liver, and adipose tissues in meat animals [seethe review by Kris-Etherton and Etherton (69)]and in the contribution of lipids to milk fatsynthesis [see the review by Palmquist (%)Iand steroidogenesis by sexual tissues [see thereview by Grummer and Carroll (51)] in cows.More recently, significant progress has beenmade concerning the mechanisms involved inthe intravascular or tissue metabolism oflipoproteins, partly because of the acquisitionof more specific analytical methods and newconcepts developed in humans and rodents.Several reviews (21, 22, 23, 106, 107) werepublished in this area during the past decade.Purification and Characterizationof Ruminant LipoproteinsLipoproteins are macromolecular complexescontaining different lipids and specialized proJournal of Dairy Science Vol. 76, No. 12. 1993teins (called apolipoproteins) that are soluble inthe fluids of the vascular systems (plasma andlymph) and in the intestinal or follicular fluids.These lipoprotein particles can be comparedwith pseudomicelles because they are all composed of hydrophilic components [PL, freecholesterol (FC),and apo] located at the surface of the particles in a unilamellar membraneand of hydrophobic lipids [TG and cholesterylesters (CE)]located in the inner core of theparticles.Differences in buoyant density, size, andapo moieties allow lipoproteins of ruminants tobe isolated and characterized. These steps arecarried out either by sequential ultracentrifugalflotation between solvent density limits proposed for human plasma (11, 19, 35, 41, 44,62, 65, 108, 113, 123, 125, 129)-completedor not by selective precipitation using sulfateddextran (19, 84) or other reagents (13, 18, 46,60,lOO)--Or by electrophoresis (19, 86, 114,122) and immunoelectrophoresis (124). Bythese methods, plasma lipoproteins ofruminants have been divided into five majordensity classes that reflect their relative lipidprotein content (Table 1): chylomicrons, verylow density lipoproteins (VLDL), intermediatedensity lipoproteins (IDL), low densitylipoproteins QDL), and high densitylipoproteins (HDL).Large variations in the metabolism of ruminant lipoproteins and in the complexity ofdistribution of their subfractions, especially inthe interval of LDL density (1.006 to 1.063 g/ml), have justified the development of highresolution methodologies.Isopycnic density gradient ultracentrifugation, which allowed subfractionation of 20lipoprotein fractions in one step according totheir hydrated density, has been used for determination of lipoprotein profiles in plasma andlymph in the preruminant calf (9, 72) and forthe separation of TG-rich lipoproteins (99, 110)and of HDL (109, 127) in the dairy cow.Filtration on agarose gel column was alsoused to isolate and to characterize plasmalipoprotein subfractions in the dairy cow bymolecular size (2, 42, 43, 47, 52, 53, 54, 83).However, immunological and electrophoreticaltechniques clearly showed that both methods,density gradient ultracentrifugation and gelfiltration, failed to separate LDL completelyfrom very light HDL particles of bovine
SYMPOSIUM:RUMINANT LIPID METABOLISM3867plasma and lymph in the density range of1.039 to 1.076 g/ml (4, 9, 43, 53, 72, 107).Occurrence of some HDL particles of sizeand buoyant density similar to that of LDLparticles is specific to the bovine and appearsduring early postnatal development (IO). Complete resolution of homogenous LDL and HDLwas finally achieved by heparin-sepharosechromatography from calf and cow plasma (29,31,70) and from calf lymph (70). Bovine HDL,devoid in apolipoprotein (apo) E, are notretarded by heparin-sepharosegel, but the LDLrich in apo B undergo selective and reversibleabsorption with the resin.Moreover, the very high saturation of thecore lipid FA of ruminant VLDL (reflectinghydrogenation processes occurring in the rumen) limited the efficiency of recovery ofVLDL particles in plasma by ultracentrifugation at temperatures c2O'C (55, 109).STRUCTURE AND FUNCTIONOF LIPOPROTEINS AND THEIRAPOLIPOPROTEIN MOIETIESChylomicronsChylomicrons are the largest (500 to 2500A) and the least dense (flotation coefficient, Sf, 400) lipoprotein particles (72) that are synthesized and secreted by the intestine after a mealcontaining fat in preruminant calves (1 1, 72)and in other ruminants (42, 59). The main roleof these TG-rich lipoproteins is to transportdietary FA (as TG) to tissues for fat storage,milk fat production, or for oxidation to produce energy (Figure 1). Chylomicron production by ruminants has long been the subject ofa controversy, probably because of the low fatcontent of ruminant diets; however,chylomicron particles clearly are synthesizedby the bovine intestine (72). Chylomicronsecretion is stimulated by increasing dietary fat(3) or dietary polyunsaturated FA (59) compared with saturated FA, which, in sheep as inrats and in humans (21), leads to secretion of amajority of VLDL particles by intestinalmucosal cells (59). Thus, in sheep under normal low fat dietary conditions ( lo g/d of TG),72.6% of the lymph lipids (577 mgh) werelocated in the VLDL fraction and 27.4% in thechylomicron fraction. After 24 h of infusion ofmaize oil (52.6% linoleic acid; 48 g/d of TG)through a duodenal cannula, 38.5% of thelymph lipids (1550 m a ) were present in theVLDL and 61.5% in the chylomicrons (59).Journal of Dairy Science Vol. 76, No. 12, 1993
3868BAUCHARTA comparison of the lipid content of bovinechylomicrons in lymph (72) and in plasma (42)(Table 1) showed that the exposure of lymphchylomicrons to serum led to a gain of freecholesterol and a loss of PL, which are probably recovered in HDL particles (3).Apolipoproteins of chylomicrons, determinedby electrophoretical and immunologicalmethods (4,9, 80, 81), are characterized by theprevalence of apo B48. This unique highapolipoprotein is presmolecular weight @fr)ent in these particles (MI 265,000 to 320,000)(72) with minor peptides of the apo C family(Mr lO,OOO), and with variable amounts of apoAI [M,28,000 (70)].VLDLBovine VLDL particles (flotation coefficient 400;density 1 . 0 0 6g/d)represent thealternative form of TG transfer in lymphaticand blood vessels from the intestine (72). Indairy cows, VLDL are probably less synthesized by the liver (9, 68) (Figure 1) than VLDLin humans.Simultaneous measurements of VLDL andchylomicron fluxes in the intestinal lymphduct, portal vein, and mesenteric artery haverecently provided evidence that the portal veinis a major export pathway of intestinal TG-richlipoproteins in the calf (36, 71). Similarly,arteriovenous measurements of TG fluxes inthe intestine of lactating dairy cows fed a highfat diet indicated a direct secretion of intestinalTG in the portal vein (25). Slow intestinal lipidabsorption in ruminants, as in rats, can lead topreferential transport of dietary FA in the portal system (79). This effect occurs inpreruminant calves that are fed milk diets thatcoagulate in the abomasum and in otherD I P O S E TISSUES/I/PERIPHERAL TISSUESsteroid synthesisFigure 1. The tissue origins and postsecretory metabolic transformation of lipoproteins within the plasma compaxtment in ruminants. HDL High density lipoproteins, LDL low density lipoproteins, TG triglyceride, CE cholesterol ester, cetp CE transfer protein, lcat 1ecithin:cholesterolacyltransferase. CHYLO chylomicron, VLDL very low density lipoproteins, Ipl lipoprotein lipase, hl hepatic lipase, FA fatty acid, FC free cholesterol.Journal of Dairy Science Vol. 76, No. 12, 1993
SYMPOSIUM: RUMINANT LIPID METABOLISMruminants that are fed diets characterized bylong rumen retention time.Plasma VLDL, lacking in fetal calves (10,44), are generally low in the bovine comparedwith VLDL in human plasma (21) becauseVLDL represent 5 % of the total lipoproteins inpreruminant calves (9, 11, 112) and .5% indairy cows (46, 52, 112). Although VLDLsecretion by the intestine can be enhanced bybiliary PL (73) and by high fat diets (125),VLDL concentrations are relatively low indairy cows, probably because of the rapid turnover of the VLDL pool (46, W),especiallyafter milking (47).Lipid Composition. Lipid VLDL are characterized by an abundance of TG in the bovine,as in other mammals, and by elevated PLcontent (Table 1). But, as in rats, VLDL inbovines are deficient in CE (9, 52, 112, 123),especially those in calf lymph (72). As forchylomicrons, FA composition of VLDL TG ishighly influenced by dietary FA at peak lipidabsorption in preruminant calves (1 1) but is notmodified by dietary source of FA in dairycows (52), probably because of the intensehydrogenation of dietary FA by rumenmicroorganisms.In preruminant calves, FA composition ofplasma VLDL TG (and chylomicron TG) ismodified during the postprandial period (11).The intense hydrolysis of plasma TG by LPLduring postprandial hyperinsulinemia led to theappearance of more saturated TG in the remaining particles and seemed to indicate selective utilization of dietary unsaturated FA byextrahepatic tissues.The FA composition of VLDL CE varies indeveloping calves (62). The low store of essential FA (mainly C18:2n-6)in calves and lambs atbirth (74, 92) is due to a very low placentatransfer of essential FA from the NEFA inmaternal plasma. Because ruminant placenta isimpermeable to other plasma lipids, CE synthesized by the intestinal and hepatic acyl:cholesterol acyltransferase (ACAT) (90) werenaturally poor in essential FA and did notcontribute to CE in LDL and HDL. As the calfgrows, selective incorporation of absorbed essential FA (mainly C18:2n-6) into plasma lecithin in @ position and specific transfer toplasma CE by 1ecithin:cholesterol acyltransferases (LCAT) (91) were hypothesized in theTG-rich lipoproteins (62). However, the rela-3 869tively lower concentrations of c1812n-6 in CEof these particles compared with those of LDLand HDL can be partially explained by ACATactivity, which is nonspecific for the essentialFA, as demonstrated in sheep (90).Apolipoprotein Content. Like other mammals, ruminants synthesize two major molecular mass forms of apo B VLDL: the large form(Mr 520,000) is referred to as apo B100, and asmaller form (M,265,000) is designed as apoB48 (9) (Table 2). These forms play a majorrole in the formation and receptor-binding ofthe particles. Details of the molecular mechanisms of apo B biosynthesis in mammals havebeen recently reviewed by Gibbons (45). Asingle gene is coded for both forms of apo B inmammals. In humans and rats,
Lipid Absorption and Transport in Ruminants ABSTRACT The objective of this paper is to re- view new insights on the biological mechanisms of absorption and transport of lipid in ruminants, especially the mod- em concepts and analytical methods used in studies on structural properties and intravascular and tissue metabolism of
Lipid nanoparticles (LNPs) are a safe vehicle for drug delivery, made of physiological or physiologically related lipids. Many different types of LNPs have been engineered, the most important being solid lipid nanoparticles (SLNs), nanostrucured lipid carriers (NLCs), lipid-- drug conjugates (LDCs) and lipid nanocapsules (LNCs).
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Toxicity from lipid peroxidation affect the liver lipid metabolism where cytochrome P-450s is an efficient catalyst in the oxidative transformation of lipid derived aldehydes to carboxylic acids adding a new facet to the biological activity of lipid oxidation metabolites. Cytochrome P-450-mediated
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distribution of lipid-based medicine. during which lipoid will use as a carrier fir delivery of poorly water soluble medicine. during this review, we have a tendency to discuss the consequences and role of lipoids and lipid digestion on drug delivery.[1] Fig. 1: Solid lipid nanoparticle. Solid Lipid Base Nano Particles
FINANCIAL ACCOUNTING : MEANING, NATURE AND ROLE OF ACCOUNTING STRUCTURE 1.0 Objective 1.1 Introduction 1.2 Origin and Growth of Accounting 1.3 Meaning of Accounting 1.4 Distinction between Book-Keeping and Accounting 1.5 Distinction between Accounting and Accountancy 1.6 Nature of Accounting 1.7 Objectives of Accounting 1.8 Users of Accounting Information 1.9 Branches of Accounting 1.10 Role .
