Intraluminal and intracellular phases of fat absorption are impaired in essential fatty acid deficiency

Lévy, Émile; Garofalo, Carole; Thibault, Louise; Dionne, Serge; D'Aoust, Louise; Lepage, Guy; Roy, Claude

doi:10.1152/ajpgi.1992.262.2.g319

Cited by 28 publications

(47 citation statements)

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“…The discrepancy regarding in vivo studies on lipoprotein clearance in EFAD rats (10,27) and our EFAD mouse model may be explained by species specificity. Previous studies have demonstrated that EFA deficiency has different effects on bile formation in rats and in mice (24,25,48).…”

Section: Discussionmentioning

confidence: 99%

Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles

Werner¹,

Havinga²,

Bos³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles. Am J Physiol Gastrointest Liver Physiol 288: G1150 -G1158, 2005. First published January 20, 2005 doi:10.1152/ajpgi.00456.2004.-Essential fatty acid (EFA) deficiency in mice decreases plasma triglyceride (TG) concentrations and increases hepatic TG content. We evaluated in vivo and in vitro whether decreased hepatic secretion of TG-rich very low-density lipoprotein (VLDL) contributes to this consequence of EFA deficiency. EFA deficiency was induced in mice by feeding an EFAdeficient (EFAD) diet for 8 wk. Hepatic VLDL secretion was quantified in fasted EFAD and EFA-sufficient (EFAS) mice using the Triton WR-1339 method. In cultured hepatocytes from EFAD and EFAS mice, VLDL secretion into medium was measured by quantifying [3 H]-labeled glycerol incorporation into TG and phospholipids. Hepatic expression of genes involved in VLDL synthesis and clearance was measured, as were plasma activities of lipolytic enzymes. TG secretion rates were quantitatively similar in EFAD and EFAS mice in vivo and in primary hepatocytes from EFAD and EFAS mice in vitro. However, EFA deficiency increased the size of secreted VLDL particles, as determined by calculation of particle diameter, particle sizing by light scattering, and evaluation of the TG-to-apoB ratio. EFA deficiency did not inhibit hepatic lipase and lipoprotein lipase activities in plasma, but increased hepatic mRNA levels of apoAV and apoCII, both involved in control of lipolytic degradation of TG-rich lipoproteins. EFA deficiency does not affect hepatic TG secretion rate in mice, but increases the size of secreted VLDL particles. Present data suggest that hypotriglyceridemia during EFA deficiency is related to enhanced clearance of altered VLDL particles. hepatic lipoprotein secretion; lipoprotein clearance; hypotriglyceridemia DEVELOPMENT OF HEPATIC STEATOSIS is a well-established manifestation of essential fatty acid (EFA) deficiency in animal models. It was first described in 1958 in rats by Alfin-Slater and Bernick (3) and in 1970 by Fukazawa et al. (12) and Sinclair and Collins (43). The excess lipid deposited in the liver during EFA deficiency can theoretically result from increased uptake of circulating lipids, enhanced de novo lipogenesis, decreased fatty acid oxidation, or decreased hepatic lipoprotein secretion, or from a combination of these. Increased hepatic lipogenesis and decreased fatty acid oxidation could indeed contribute, because polyunsaturated fatty acids are physiological suppressors of fatty acid synthesis (4, 31) through downregulation of SREBP1c (16, 42, 51) and inducers of hepatic fatty acid oxidation through activation of PPAR␣, respectively. The quantitative contribution of increased lipogenesis and decreased oxidation to EFA deficiency-induced hepatic steatosis has not been established. Whereas the effects of EFA deficiency on induction of hepatic steatosis are fairly consistent in the literature, the consequences for he...

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Section: Discussionmentioning

confidence: 99%

Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles

Werner¹,

Havinga²,

Bos³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Indeed, as previously demonstrated for the oxidative status [15], pulmonary dysfunction seems to be more important than nutritional disorders in controlling the plasma FA profile, except for EFA deficiency, because the BMI affects linoleic acid positively and palmitoleic acid negatively. This point deserves careful investigation because diet is the only source of EFAs and because fat malabsorption is commonly thought to cause EFA deficiency, while EFA deficiency is also a known cause of fat malabsorption [33,34]. Furthermore, the transition from pulmonary inflammation to systemic inflammation should also be considered.…”

Section: Discussionmentioning

confidence: 99%

Plasma fatty acids and lipid hydroperoxides increase after antibiotic therapy in cystic fibrosis

Durieu¹,

Abbas‐Chorfa²,

Drai³

et al. 2007

European Respiratory Journal

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The present authors investigated whether cystic fibrosis is linked to a defect in fatty acids and assessed the impact of the main patients' characteristics on the levels of several fatty acids, mostly during respiratory exacerbation and after antibiotic therapy.Fatty acid phospholipid and cholesteryl ester levels were measured in stable-state patients and controls. No differences were found concerning either the fractions of palmitic and oleic acids or the cholesteryl esters of a-linolenic and arachidonic acids. However, phospholipids of a-linolenic and arachidonic acids, as well as cholesteryl esters and phospholipids of stearic and linoleic acids, were lower in patients than in controls, but fractions of dihomo-c-linolenic, docosatetraenoic, docosapentaenoic, palmitoleic and eicosatrienoic acids were higher.Fatty acid levels, oxidative stress markers, nutrients, body mass index and forced expiratory volume in one second (FEV1) were measured in patients before and after antibiotic courses for bronchial exacerbation. After adjustments, palmitic, stearic, a-linolenic, linoleic, arachidonic, palmitoleic and oleic acids generally decreased during exacerbation but almost all increased after antibiotic courses. Nearly all fractions increased along with FEV1 and a positive relationship linked fatty acids to lipid hydroperoxides.There was no general drop in fatty acids. Patients' fatty acid profiles depended on the pulmonary function and the inflammation state.

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“…In Vitro Experiments with BMS-200150 -ApoB synthesis was assessed in everted rat intestine, as described previously (44). Then, 300 Ci of […”

Section: Methodsmentioning

confidence: 99%

Localization of Microsomal Triglyceride Transfer Protein in the Golgi

Lévy¹,

Stan²,

Delvin³

et al. 2002

Journal of Biological Chemistry

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Although a critical role of microsomal transfer protein (MTP) has been recognized in the assembly of nascent apolipoprotein B (apoB)-containing lipoproteins, it remains unclear where and how MTP transfers lipids in the secretory pathway during the maturational process of apoB lipidation. The aims of this study were to determine whether MTP functions in the secretory pathway as well as in the endoplasmic reticulum and whether its large 97-kDa subunit interacts with the small 58-kDa protein disulfide isomerase (PDI) subunit and apoB, particularly in the Golgi apparatus. Using a high resolution immunogold approach combined with specific polyclonal antibodies, the large and small subunits of MTP were observed over the rough endoplasmic reticulum and the Golgi. Double immunocytochemical detection unraveled the colocalization of MTP and PDI as well as MTP and apoB in these same subcellular compartments. To confirm the spatial contact of these proteins, Golgi fractions were isolated, homogenized, and incubated with an anti-MTP large subunit antibody. Immunoprecipitates were applied on SDS-PAGE and then transferred on to nitrocellulose. Immunoblotting the membrane with PDI and apoB antibodies confirmed the colocalization of these proteins with MTP. Furthermore, MTP activity assay disclosed a substantial triglyceride transfer in the Golgi fractions. The occurrence of membrane-associated apoB in the Golgi, coupled with its interaction with active MTP, suggests an important role for the Golgi in the biogenesis of apoB-containing lipoproteins.Lipids constitute the most calorically dense dietary nutrients. They must undergo emulsification within the intestinal lumen, cell membrane permeation, intracellular esterification, and incorporation into chylomicrons before reaching the circulatory system (for reviews, see Refs. 1-4). Despite significant progress, our understanding of the complex biosynthetic process involved in the formation and secretion of triglyceride-rich lipoprotein particles remains rather fragmentary. In particular, we know little about the sequential multistep assembly of apolipoproteins and lipids or the topology of the proteins in intracellular organelles implicated in lipoprotein production.The study of naturally occurring mutations and genetic variations in humans has greatly contributed to the identification of the proteins essential to the synthetic pathway and to the delineation of key metabolic mechanisms (5-11). Inherited disorders of apolipoprotein B (apoB) 1 and microsomal transfer protein (MTP) deficiency have provided a unique source for delineating, at least partially, the role of these specific proteins as well as elucidating the intracellular mechanisms that result in lipid absorption and transport (5-11). The addition of core lipid to the nascent lipoprotein particle is thought to occur in conjunction with the translation and translocation of apoB in the ER (12)(13)(14)(15). During this process, apoB remains tightly bound to the ER membrane, where it is folded. The initial complement of lipid...

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Intraluminal and intracellular phases of fat absorption are impaired in essential fatty acid deficiency

Cited by 28 publications

References 0 publications

Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles

Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles

Plasma fatty acids and lipid hydroperoxides increase after antibiotic therapy in cystic fibrosis

Localization of Microsomal Triglyceride Transfer Protein in the Golgi

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