Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation

Werner, Anniek; Minich, Deanna M.; Havinga, Rick; Bloks, Vincent W.; Goor, Harry van; Kuipers, Folkert; Verkade, Henkjan J.

doi:10.1152/ajpgi.00094.2002

Cited by 27 publications

(58 citation statements)

References 34 publications

(23 reference statements)

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“…No obstante, en todas las dietas la absorción aparente fue muy elevada y la diferencia entre los grupos no condujo a modificaciones en el peso corporal de los diferentes animales. Otros autores (48,49) reportaron que los animales con dietas DAGE presentaron una menor absorción de grasa, y consecuentemente una menor ganancia de peso corporal. Es probable que las diferencias sean atribuidas a los diseños experimentales, dado que en nuestro modelo las ratas fueron sometidas a una deficiencia marginal de AGE y no a una profunda deficiencia como en otros trabajos.…”

Section: Discussionunclassified

Efectos de los conjugados del ácido linoleico sobre la incorporación tisular de ácidos grasos y metabolismo lipídico en ratas deficientes en ácidos grasos esenciales

Fariña¹,

González²,

Latorre³

et al. 2014

FABICIB

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Section: Discussionunclassified

Efectos de los conjugados del ácido linoleico sobre la incorporación tisular de ácidos grasos y metabolismo lipídico en ratas deficientes en ácidos grasos esenciales

Fariña¹,

González²,

Latorre³

et al. 2014

FABICIB

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“…Total bile salt concentrations were measured using the 3a-hydroxysteroid dehydrogenase method (18). Biliary bile acid and phospholipid fatty acid compositions were determined by capillary gas chromatography after their conversion into methyl ester-trimethylsilyl ether derivatives or methyl esters, respectively, exactly as described (19,20). To determine bile flow, the gallbladder of the mice was cannulated under isoflurane anesthesia after distal ligation of the common bile duct.…”

Section: Plasma and Bile Lipid Analysismentioning

confidence: 99%

“…The superior hypocholesterolemic properties of dietary PUFAs relative to dietary MUFAs suggests that endogenous MUFA production affects the dietary requirement of PUFAs. Although treatment of SCD1 1/1 mice with an essential fatty acid-deficient diet for 8 weeks does not cause hypercholesterolemia or cholestasis (20), the effect of an essential fatty acid-deficient diet in SCD1 2/2 mice has not been explored previously. Future research will be necessary to further elucidate the mechanism of hepatic dysfunction and dyslipidemia observed in this model as well as to identify the PUFA species essential for the prevention of this phenotype.…”

Section: In Vlf Scd1mentioning

confidence: 99%

Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet

Flowers

Groen

Oler

et al. 2006

Journal of Lipid Research

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Stearoyl-coenzyme A desaturase 1-deficient (SCD1 2/2 ) mice have impaired MUFA synthesis. When maintained on a very low-fat (VLF) diet, SCD12/2 mice developed severe hypercholesterolemia, characterized by an increase in apolipoprotein B (apoB)-containing lipoproteins and the appearance of lipoprotein X. The rate of LDL clearance was decreased in VLF SCD1 2/2 mice relative to VLF SCD11/1 mice, indicating that reduced apoB-containing lipoprotein clearance contributed to the hypercholesterolemia. Additionally, HDL-cholesterol was dramatically reduced in these mice. The presence of increased plasma bile acids, bilirubin, and aminotransferases in the VLF SCD1 2/2 mice is indicative of cholestasis. Supplementation of the VLF diet with MUFA-and PUFA-rich canola oil, but not saturated fat-rich hydrogenated coconut oil, prevented these plasma phenotypes. However, dietary oleate was not as effective as canola oil in reducing LDL-cholesterol, signifying a role for dietary PUFA deficiency in the development of this phenotype. These results indicate that the lack of SCD1 results in an increased requirement for dietary unsaturated fat to compensate for impaired MUFA synthesis and to prevent hypercholesterolemia and hepatic dysfunction. Therefore, endogenous MUFA synthesis is essential during dietary unsaturated fat insufficiency and influences the dietary requirement of PUFA. Although dietary saturated fat is generally regarded as hypercholesterolemic, the roles of de novo synthesized saturated fatty acids and MUFAs in the regulation of plasma cholesterol levels have not been thoroughly investigated (1-3). Stearoyl-coenzyme A desaturase 1 (SCD1) is a central enzyme in lipid metabolism that catalyzes the desaturation of palmitoyl-CoA and stearoyl-CoA to palmitoleoyl-CoA and oleoyl-CoA, respectively (4). The dietary requirement for MUFA, if any, is confounded by the capacity for endogenous MUFA synthesis. Furthermore, under certain metabolic conditions, both dietary and endogenously synthesized MUFAs have been hypothesized to influence the dietary requirement for certain PUFAs (5). SCD1-deficient (SCD1 2/2 ) mice have impaired MUFA synthesis and are a useful animal model to study the influence of de novo synthesized MUFAs on lipoprotein metabolism and the requirement for dietary unsaturated fat.Four SCD isoforms (SCD1-SCD4), encoded by different genes, have been identified in the mouse (4). However, SCD1 is the most abundant isoform expressed in lipogenic tissues, such as liver and adipose tissue (4). SCD1 gene expression is regulated by both hormones (insulin, leptin) and by a variety of nutrients such as cholesterol, glucose, fructose, and PUFAs (4, 6-11). This transcriptional regulation involves several transcription factors, including carbohydrate response element binding protein, sterolregulatory element binding protein-1c (SREBP-1c), and liver X receptor, highlighting the importance of SCD1 activity for the adaptation to different metabolic demands (12, 13). SCD1 activity influences the fatty acid composi-

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“…Fatty acid methyl esters were separated and quantified by gasliquid chromatography (GLC) on a Hewlett Packard gas chromatograph model 6890, equipped with a 50 m ϫ 0.2 mm Ultra 1 capillary column (Hewlett Packard, Palo Alto, CA) and a flame ionization detector as described previously (24). We verified the purity of AA and DHA peaks as separated by GLC, using a gas chromatography-mass spectrometer (GC-MS; Finnigan MAT SSQ7000), equipped with either a 50 m ϫ 0.2 mm Ultra 1 capillary column or a 50 m ϫ 0.22 mm BPX70 capillary column (SGE, Weiterstadt, Germany).…”

Section: Analytical Techniquesmentioning

confidence: 99%

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

Werner¹,

Bongers²,

Bijvelds

et al. 2004

Journal of Lipid Research

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A deficiency of essential fatty acids (EFA) is frequently described in cystic fibrosis (CF), but whether this is a primary consequence of altered EFA metabolism or a secondary phenomenon is unclear. It was suggested that defective long-chain polyunsaturated fatty acid (LCPUFA) synthesis contributes to the CF phenotype. To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects LCPUFA synthesis, we quantified EFA metabolism in cftr ؊ / ؊ CAM and cftr ؉ / ؉ CAM mice. Effects of intestinal phenotype, diet, age, and genetic background on EFA status were evaluated in cftr ؊ / ؊ CAM mice, ⌬ F508/ ⌬ F508 mice, and littermate controls. EFA metabolism was measured by 13 C stable isotope methodology in vivo. EFA status was determined by gas chromatography in tissues of cftr ؊ / ؊ CAM mice, ⌬ F508/ ⌬ F508 mice, littermate controls, and C57Bl/6 wild types fed chow or liquid diet. After enteral administration of [ 13 C]EFA, arachidonic acid (AA) and docosahexaenoic acid (DHA) were equally 13 C-enriched in cftr ؊ / ؊ CAM and cftr ؉ / ؉ CAM mice, indicating similar EFA elongation/desaturation rates. LA, ALA, AA, and DHA concentrations were equal in pancreas, lung, and jejunum of chow-fed cftr ؊ / ؊ CAM and ⌬ F508/ ⌬ F508 mice and controls. LCPUFA levels were also equal in liquid diet-weaned cftr ؊ / ؊ CAM mice and littermate controls, but consistently higher than in age-and diet-matched C57Bl/6 wild types. We conclude that cftr ؊ / ؊ CAM mice adequately absorb and metabolize EFA, indicating that CFTR dysfunction does not impair LCPUFA synthesis. A membrane EFA imbalance is not inextricably linked to the CF genotype. EFA status in murine CF models is strongly determined by genetic background. -Werner, A., M. E. J. Bongers, M. J. Bijvelds, H. R. de Jonge, and H. J. Verkade. No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis.

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Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation

Cited by 27 publications

References 34 publications

Efectos de los conjugados del ácido linoleico sobre la incorporación tisular de ácidos grasos y metabolismo lipídico en ratas deficientes en ácidos grasos esenciales

Efectos de los conjugados del ácido linoleico sobre la incorporación tisular de ácidos grasos y metabolismo lipídico en ratas deficientes en ácidos grasos esenciales

Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high-carbohydrate diet

No indications for altered essential fatty acid metabolism in two murine models for cystic fibrosis

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