scholarly journals Gastrointestinal morphology and absorption of monosaccharides in fowls conditioned to different types and levels of dietary fibre

1992 ◽  
Vol 67 (1) ◽  
pp. 77-89 ◽  
Author(s):  
C. J. Savory
Keyword(s):  
Dietary Fibre ◽  
Dietary Treatment ◽  
Basal Diet ◽  
Sugar Uptake ◽  
Fluid Loss ◽  
Standard Diet ◽  
Sugar Absorption ◽  
Body Tissues ◽  
Intestine Length

To test a possible influence of dietary fibre on intestinal sugar uptake, rates of absorption of 10 mm-d[U-14C] glucose and 10 mm-d-[U-14C] xylose were measured in either jejunum or (distal) caecum, by in vivo lumen perfusion, in immature female fowls preconditioned to a standard diet containing (g/kg) either 0, 100, 200 or 400 added dried grass, 200 powdered cellulose, or 200 grass with a polysaccharidase enzyme supplement. When birds were killed after perfusion, dimensions of (unperfused) parts of their alimentary tracts were determined, and recoveries of 14C radioactivity in some body tissues were compared with measured activities absorbed. On average, absorption of glucose was 1·9 and 1·2 times faster than xylose in jejunum and caecum respectively, although these differences varied with dietary treatment and order of perfusion. Increasing grass in the diet caused significant changes in xylose absorption rate in both jejunum and caecum, but only when it was perfused before glucose. With any one sugar and intestinal segment, mean rates of absorption were correlated positively with corresponding mean rates of fluid loss from perfusate. Although their influence on sugar absorption was not well defined, the dietary fibre treatments had more pronounced effects on gross dimensions of parts of the alimentary tract and, hence, potentially on total rates of absorption. Compared with the basal diet, addition of 100, 200 or 400 g grass/kg or 200 g cellulose/kg caused significant increases in small intestine length while 200 g grass/kg with supplementary enzyme did not, and combined caecal length increased with the 400 g grass/kg and the supplementary enzyme treatments. Absorbed 14C activity was recovered in plasma after jejunal perfusions but not caecal ones, whereas it was recovered in liver and in the flushed perfused segment after both types of perfusion. Since there was overlap in absorption rates between jejunum and caecum, this result suggests that the liver may be able to distinguish and treat differently compounds absorbed in the two regions.

scholarly journals Effects of Thymol and Thymol α-D-Glucopyranoside on Intestinal Function and Microbiota of Weaned Pigs

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 329
Author(s):  
Noémie Van Noten ◽  
Jeroen Degroote ◽  
Elout Van Liefferinge ◽  
Bernard Taminiau ◽  
Stefaan De Smet ◽  
...  
Keyword(s):  
Small Intestine ◽  
Biological Effects ◽  
Intestinal Barrier ◽  
Stomach Contents ◽  
Dietary Treatment ◽  
Basal Diet ◽  
Intestinal Barrier Function ◽  
Distal Small Intestine ◽  
Great Relative Abundance

The present study evaluated gluco-conjugation as a measure to delay thymol absorption and enhance its antimicrobial activity in the gut of weaned piglets. The three dietary treatments consisted of a basal diet without additives (TCON), supplemented with thymol at 3.7 mmol/kg dry matter (TTHY), or with an equimolar amount of thymol α-D-glucopyranoside (TTαG). Each dietary treatment was replicated in 6 pens with 2 piglets per pen (n = 12 for analytical parameters) and was supplemented for 14 days. The total (free plus gluco-conjugated) thymol concentrations in the stomach contents were 14% lower in TTαG as compared to TTHY piglets. Neither of the additives could be detected further down the gut. E.coli counts in the proximal small intestine were significantly lower in TTHY than in TTαG pigs (3.35 vs. 4.29 log10 CFU/g); however, other bacterial counts and their metabolites were unaffected by treatment. A metagenomic bacterial analysis revealed a great relative abundance of Lactobacillus spp. in the distal small intestine (range 88.4–99.9%), irrespective of treatment. The intestinal barrier function was improved by TTHY, but not TTαG, compared to TCON. In conclusion, gluco-conjugation did not result in higher thymol concentrations in the gut, but conversely, it seemed to diminish the biological effects of thymol in vivo.

scholarly journals Determination of digestible energy values and fermentabilities of dietary fibre supplements: a European interlaboratory study in vivo

1995 ◽  
Vol 74 (3) ◽  
pp. 289-302 ◽  
Author(s):  
G. Livesey ◽  
T. Smith ◽  
B. O. Eggum ◽  
I. H. Tetens ◽  
M. Nyman ◽  
...  
Keyword(s):  
Sugar Beet ◽  
Dietary Fibre ◽  
Direct Determination ◽  
Basal Diet ◽  
Metabolizable Energy ◽  
Digestible Energy ◽  
Maize Bran ◽  
Heats Of Combustion

The performance of methods to determine energy conversion factors for dietary fibre (DF) supplements and fermentability (D) values of their non-starch polysaccharides (NSP) was investigated. Heats of combustion, digestible energy (DE) and D values were determined on five DF supplements in five European laboratories on five separate occasions. In each instance the DF supplements were fed to juvenile male VVistar rats at two doses, 50 and 100 g/kg basal diet, for 3 weeks with food and faeces collected in the 3rd week. Among-laboratory variations in heats of combustion (DHC<) were <2%. DE values (kJ/g dry weight) at the upper and lower doses respectively were: 10·4 and 9·9 for a high-methoxyl apple pectin, 9·5 and 9·4 for a sugar-beet DF supplement, 12·2 and 12·7 for soyabean DF supplement, 38 and 4·0 for maize bran, and 0·3 and 0·3 for Solka-floc cellulose. Variations among laboratories, among occasions and among animals were <1, <2 and <2·5 kJ/g respectively. The among-occasion: among-laboratory variance ratio for DE was 0·5, suggesting the method performed equally well in all laboratories. There was no evidence of learning or fatigue in the performance of the method. D values were also independent of dose and at the high and lower doses were: pectin 0·92 and 0·95, sugar-beet NSP 0·68 and 0·68, soyabean NSP 0·86 and 0·88, maize bran 0·17 and 0·18, cellulose 0·07 and 0·06. Among-laboratory variance tended to increase with decreasing fermentability and ranged from 0·03 to 0·18. The DE and D data were not significantly different from a previously proposed relationship DE = 0·7 × DHc × D, where DHc is the heat of combustion of the supplement. We conclude that while the among-laboratory variation in the D of difficult-to-ferment NSP is too large for the reliable prediction of energy value the method for the direct determination of DE is both reproducible and repeatable, that DE is independent of dosage of DF supplement up to 100 g/kg diet, and that it is safe to discriminate between energy values with a precision of 3 kJ/g. The conversion of both DE and D to net metabolizable energy for the purpose of food labelling, tables and databases is described.

scholarly journals Utilization of α-amylase (EC 3.2.1.1) resistant maize and pea (Pisum sativum) starch in the rat

1989 ◽  
Vol 61 (2) ◽  
pp. 291-300 ◽  
Author(s):  
R. M. Faulks ◽  
Susan Southon ◽  
G. Livesey
Keyword(s):  
Pisum Sativum ◽  
Adaptive Response ◽  
Dietary Treatment ◽  
Basal Diet ◽  
Experimental Period ◽  
Food Ration ◽  
Carbohydrate Source ◽  
Intestinal Length ◽  
Resistant Starches

1. The extent of utilization of α-amylase (EC 3.2.1.1)-resistant retrograded starches in vivo was assessed in male Wistar rats (about 100 g body-weight). All animals were given a fibre-free semi-synthetic basal diet (SS) containing sucrose as the only carbohydrate source, ad lib., for 13 d. On day 14, after an overnight fast, rats were allocated to one of five dietary treatments (n 30):1, fibre-free basal SS diet; 2-5, basal SS diet supplemented with 100 g sucrose, Solka floc (cellulose), resistant maize starch (RCS) or resistant pea (Pisum sativum) starch (RPS)/kg diet. Animals allocated to each dietary treatment were divided into three groups of ten rats which were given the appropriate diet for 8 or 9, 17 or 18 and 29 or 30 d (8/9, 17/18 or 29/30 d groups respectively). Rats were fed on 12 g diet/d (treatment 1) or 13.2 g diet/d (treatments 2-5) for the first 20 d, and 14 or 15.4 g/d respectively until the end of the experiment. Rats fed on the supplemented basal diets were thus given 10% more food to allow for the addition of the test carbohydrate. Faecal carbohydrate excretion was determined at intervals in the 17/18 d groups. At the end of each experimental period animals were killed after consuming their daily food ration and small intestinal length, weight of caecal and ileal contents and tissue, and pH of caecal contents measured. The amount of carbohydrate in the caecal and ileal contents from the 8/9 and 17/18 d groups was determined.2. Weights of ileal and caecal contents, caecal tissue and faecal output were significantly greater at all time points for rats fed on the resistant starches compared with those fed on basal and sucrose-supplemented diets. Values were higher for RPS-fed rats than for RCS-fed rats.3. The quantity of carbohydrate recovered from ileal and caecal contents showed that both RCS and RPS were partially digested and absorbed as carbohydrate, but that RPS was digested to a lesser extent.4. The concentration of carbohydrate decreased between the ileal and caecal sites when RPS and RCS were given but was essentially unchanged when cellulose was given. This is consistent with rapid fermentation of a fraction of these starches.5. Faecal carbohydrate elimination in the 17/18 d groups fed on RCS and RPS declined with time, which suggested an adaptive response resulting in increased utilization of the starches. This adaptive response was slower in the RPS-fed rats than the RCS-fed rats.6. The present study indicates that, in the rat, there are significant differences in the utilization of resistant starches from different sources.

MONOCYTE-MACROPHAGE PROCOAGULANT ACTIVITY AND ENDOTHELIAL THROMBOMODULIN IN RABBITS FED AN ATHEROGENIC DIET

1987 ◽  
Author(s):  
P Montemuro ◽  
N Pasquetto ◽  
E Curci ◽  
M Colucci ◽  
A Semeraro
Keyword(s):  
Dietary Treatment ◽  
Atherogenic Diet ◽  
Mononuclear Phagocytes ◽  
Procoagulant Activity ◽  
Dietary Fats ◽  
Standard Diet ◽  
Functional Changes ◽  
Atherosclerotic Lesions

Mononuclear phagocytes (M) and vascular cellsmay participate in the events that lead tothe development of atherosclerotic lesions. We have studied the procoagulant activity (PCA) of M and thrombomodulin (TM)-like activityofendothelial cells in 15 rabbits fed an atherogenic diet for 4-5 weeks and in 15 rabbits fed a standard diet. Peripheral blood and spleen M were tested for PCA immediately after isolation (basal PCA) and following in vitro stimulation by bacterial endotoxin, using a one-stage clotting assay. TM-like activity was measured by the rate of (bovine) protein C activation induced by catalytic concentrations of thrombin in the presence of aortic rings (1cm long) and CaCl2 Blood M expressed negligible basal PCA (< 1 U/105 M) both in hyperlipaemic and controlrabbits. Endotoxin-induced PCA was not significantly different in the two groups. In contrast, dietary treatment resulted in a significant increase in the basal PCA of spleen M (67.6 ± 13.5 vs 26.5 ± 5.4 U/105 M, pcO.Ol). Moreover, spleen M fromtreated animals produced significantly more PCA than controls (p<0.01) in response to endotoxin. When rabbits were given a single injection of endotoxin, spleen M harvested 60 min after the injection from hyperlipaemicanimals expressed 3 times more PCA (p<0.05, n=6) than did cells from controls. In all instances PCA was identified as tissue factor. TM activity associated with the endothelium was not different in the two groups of animals notwithstanding the presence of fatty streaks on the aortic endothelium of treated rabbits. It is suggested that dietary fats maycause early functional changes in M that leadto increased PCA production both in vivo and in vitro.These data may be relevant to an understanding of the role of M in the pathogenesis of atherosclerosis.

Interactions of insulin-like growth factor (IGF)-II and growth hormone in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice

1997 ◽  
pp. 701-708 ◽  
Author(s):  
A Blackburn ◽  
RA Dressendorfer ◽  
WF Blum ◽  
M Erhard ◽  
G Brem ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Transgene Expression ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
Igf I ◽  
Igf Binding ◽  
B Mice

To study interactions between insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo, we crossed hemizygous transgenic mice carrying phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II fusion genes with hemizygous PEPCK-bovine GH (bGH) transgenic mice. Offspring harbouring both transgenes (IB), the IGF-II transgene (I) or the bGH transgene (B), and non-transgenic littermates (C) were obtained. Blood samples were taken before (end of week 12) and after (end of week 14) the mice had received a diet high in protein and low in carbohydrates to stimulate PEPCK promoter-controlled transgene expression. Mean serum GH concentrations of both B and IB mice corresponded to 900 ng/ml and increased more than twofold (P < 0.001) after 1 week of the high-protein diet. GH concentrations in controls and I mice were less than 20 ng/ml. Serum IGF-II concentrations in I and IB mice were three-to fourfold higher than those in C and B mice. Whereas IGF-II concentrations were not changed by the high-protein diet in the last two groups, serum IGF-II increased significantly in I (P < 0.001) and IB mice (P < 0.05). This increase was significantly (P < 0.05) less pronounced in IB than in C and I mice. Circulating IGF-I concentrations were about twofold (P < 0.001) higher in B and IB than in C and I mice, and showed a tendency to be lower in I than in C and in IB than in B mice when animals were maintained on the standard diet. The high-protein diet did not change circulating IGF-I concentrations in controls and B mice, but resulted in a significant reduction of serum IGF-I concentrations in I (P < 0.05) and IB mice (P < 0.001). Consequently, after PEPCK-IGF-II transgene expression was stimulated, serum IGF-I concentrations were significantly (P < 0.05) lower in I than in C and in IB than in B mice. Serum IGF-binding protein (IGFBP)-2 concentrations were significantly (P < 0.05) higher in I mice than in all other groups when mice were maintained on the standard diet, with a tendency to reduced IGFBP-2 concentrations in B mice. After the high-protein diet, serum IGFBP-2 concentrations did not change in C and I mice, but increased by two- to threefold in B and IB mice (P < 0.001). Serum IGFBP-3 concentrations tended to be greater in B and IB than in C and I mice, but these differences were mostly not significant. IGFBP-4 concentrations were significantly (P < 0.001) increased by GH overproduction in B and IB mice. Our data suggest that the reduction in circulating IGF-I concentrations by increased IGF-II is most probably due to the limited serum IGF binding capacity and the short half-life of free IGFs, rather than to a reduction in GH-dependent IGF-I production. Effects of GH overproduction on serum IGFBP-2 concentrations depend on dietary factors and may be both inhibitory and stimulatory.

scholarly journals Dietary sodium requirement determined for juvenile hybrid tilapia (Oreochromis niloticus × O. aureus) reared in fresh water and seawater

2004 ◽  
Vol 91 (4) ◽  
pp. 585-590 ◽  
Author(s):  
Shi-Yen Shiau ◽  
Li-Shan Lu
Keyword(s):  
Weight Gain ◽  
Atpase Activity ◽  
Fresh Water ◽  
Oreochromis Niloticus ◽  
Polynomial Regression ◽  
Control Diet ◽  
Dietary Treatment ◽  
Basal Diet ◽  
Dietary Sodium ◽  
Whole Body

Two 8-week feeding trials were conducted to determine the dietary Na requirement for juvenile hybrid tilapia (Oreochromis niloticus × O. aureus) reared in fresh water and seawater. In each experiment, NaCl was added to the basal diet at 0, 0·5, 1, 2, 3, 5, or 7g Na/kg diet (fresh water) and at 0, 0·2, 0·5, 0·8, 1·2, 1·5, 2, or 3g Na/kg diet (seawater). Each diet was fed to three replicate groups of fish, individual fish initially weighing 0·69 (se 0·01) g, in a closed, recirculating rearing system. In fresh water, the tilapia fed the diet supplemented with 2g Na/kg diet had significantly (P<0·05) greater weight gain than the fish fed the diets supplemented with ≥3 and ≤0·5g Na/kg diet. Feed efficiency (FE) in fish generally followed the weight-gain pattern. Gill Na+–K+ ATPase activity was highest in the fish fed the diets supplemented with 1–3g Na/kg diet, followed by the fish fed the diet with 7g Na/kg diet and lowest in the fish fed the unsupplemented control diet. In seawater, the weight gain, FE and gill Na+–K+ ATPase activity in fish were not affected by the dietary treatment. Analysis by polynomial regression of weight gain, by broken-line regression of gill Na+–K+ ATPase activity and by linear regression of whole-body Na retention of the fish reared in fresh water, indicated that the adequate dietary Na concentration for tilapia is about 1·5g/kg diet. The present study also suggests that no dietary Na is required for tilapia reared in seawater.

scholarly journals Experimental model for in vivo determination of dietary fibre and its effect on the absorption of nutrients in the small intestine

1981 ◽  
Vol 45 (2) ◽  
pp. 283-294 ◽  
Author(s):  
Ann-Sofie Sandberg ◽  
H. Andersson ◽  
B. Hallgren ◽  
Kristina Hasselblad ◽  
B. Isaksson ◽  
...  
Keyword(s):  
Small Intestine ◽  
Wheat Bran ◽  
Dietary Fibre ◽  
Dry Weight ◽  
Direct Analysis ◽  
Fresh Weight ◽  
Wet Weight ◽  
Definition Of

1. An experimental model for the determination of dietary fibre according to the definition of Trowell et al. (1976) is described. Food was subjected to in vivo digestion in ileostomy patients, and the ileostomy contents were collected quantitatively, the polysaccharide components of which were analysed by gas–liquid chromatography and the Klason lignin by gravimetric determination. The model was used for the determination of dietary fibre in AACC (American Association of Cereal Chemists), wheat bran and for studies on the extent of hydrolysis of wheat-bran fibre in the stomach and small intestine. The effect of wheat bran on ileostomy losses of nitrogen, starch and electrolytes was also investigated.2. Nine patients with established ileostomies were studied during two periods while on a constant low-fibre diet. In the second period 16 g AACC wheat bran/d was added to the diet. The ileostomy contents and duplicate portions of the diet were subjected to determinations of wet weight, dry weight, water content, fibre components, starch, N, sodium and potassium.3. The wet weight of ileostomy contents increased by 94 g/24 h and dry weight by 10 g/24 h after consumption of bran. The dietary fibre of AACC bran, determined as the increase in polysaccharides and lignin of ileostomy contents after consumption of bran, was 280 g/kg fresh weight (310 g/kg dry matter). Direct analysis of polysaccharides and lignin in bran gave a value of 306 g/kg fresh weight. Of the added bran hemicellulose and cellulose 80–100% and 75–100% respectively were recovered in ileostomy contents. There was no significant difference between the two periods in amount of N, starch and K found in the ileostomy contents. The Na excretion increased during the ‘bran’ period and correlated well with the wet weight of ileostomy contents.4. In conclusion, it seems probable that determination of dietary fibre by in vivo digestion in ileostomy patients comes very close to the theoretical definition of dietary fibre, as the influence of bacteria in the ileum seems small. Bacterial growth should be avoided by using a technique involving the change of ileostomy bags every 2 h and immediate deep-freezing of the ileostomy contents. True dietary fibre can be determined by direct analysis of polysaccharides and lignin in the food, at least in bran. Very little digestion of hemicellulose and cellulose from bran occurs in the stomach and small bowel. The 10–20% loss in some patients may be due to digestion by the gastric juice or to bacterial fermentation in the ileum, or both. The extra amount of faecal N after consumption of bran, reported by others, is probably produced in the large bowel.

Serological biomarkers of zearalenone exposure in beef heifers receiving anti-mycotoxin additive

2020 ◽  
pp. 1-10
Author(s):  
C. Tonini ◽  
M.S. Oliveira ◽  
E.B. Parmeggiani ◽  
D.A.F. Sturza ◽  
A.O. Mallmann ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Biological Fluids ◽  
Basal Diet ◽  
Beef Heifers ◽  
Efficacy Evaluation ◽  
Limit Of Quantification ◽  
In Vivo Measurement ◽  
Significant Difference ◽  
Serological Biomarkers

The inclusion of anti-mycotoxin additives (AMA) in the diet of production animals has been widely used to avoid mycotoxin exposure. In order to confirm the efficacy of such products in vivo, measurement of mycotoxins and/or their metabolites in biological fluids is preconized. This study aimed at determining the serological biomarkers of zearalenone (ZEN), α-zearalenol, β-zearalenol, α-zearalanol, β-zearalanol (β-ZAL) and zearalanone, to evaluate the efficacy of an AMA in beef heifers. The trial lasted 37 days: 11 days of adaptation, 21 days of actual experiment, and 5 days of regression. Twenty-four heifers were randomly assigned to receive one of the following treatments (n=6/group): (T1) basal diet (control); (T2) basal diet + 5 mg/kg of ZEN; (T3) basal diet + 5 mg/kg of ZEN + 2.5 kg/t of AMA; and (T4) basal diet + 5 mg/kg of ZEN + 5.0 kg/t of AMA. Blood sampling was performed on different days after the diet was given. The samples were centrifuged to obtain the blood serum, and then analysed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). β-ZAL was detected above the limit of quantification both in the unconjugated (>0.60 ng/ml) and conjugated (>0.90 ng/ml) forms. The remaining metabolites presented concentrations under the limit of detection. In the efficacy evaluation of the AMA, there was no significant difference (P>0.05) between the treatments with and without additive at the tested levels of inclusion. Thus, β-ZAL may be employed as a biomarker of ZEN exposure via diet to evaluate the efficacy of an AMA through serological parameters. The technique applied in this study proved to be an adequate alternative for in vivo confirmation of the efficacy of products in adsorbing the toxin.

Equilibrium distribution of radioxenon in tissue: xenon-hemoglobin association curve

1961 ◽  
Vol 16 (6) ◽  
pp. 1065-1070 ◽  
Author(s):  
Hadley L. Conn
Keyword(s):  
Partition Coefficients ◽  
Equilibrium Distribution ◽  
Hemoglobin Concentration ◽  
Gas Diffusion ◽  
In Vivo Studies ◽  
Diffusion Method ◽  
Body Tissues ◽  
Gas Diffusion Method

In vitro and in vivo studies were made of the equilibrium distribution of radioxenon in various organs and tissues of the dog and the xenon uptake compared with a water standard. Tissue-blood partition coefficients were calculated. The radioxenon-hemoglobin association curve was determined for dog and human hemoglobin and methemoglobin. The uptake of radioxenon by blood, due in particular to xenon-hemoglobin affinity, was appreciably greater than uptake either by water or by most other body tissues. Fat and brain were notable exceptions. Consequently, tissue-blood partition coefficients were about eight for fat, one for brain, and significantly less than one for other tissues studied. Acceptable accuracy for blood flow determinations with a radioxenon inert gas diffusion method would seem to depend on the use of a partition coefficient correction in turn corrected at least for the existing hemoglobin concentration. The uptake of xenon by hemoglobin had the characteristics of a solubility or a quasi-solubility phenomenon. The problem of the nature of the interaction is apparently not resolved. Submitted on June 19, 1961

scholarly journals Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009891
Author(s):  
Baocai Xie ◽  
Xiaochen Shi ◽  
Yan Li ◽  
Bo Xia ◽  
Jia Zhou ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
De Novo ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherogenic Diet ◽  
Standard Diet ◽  
Low Levels ◽  
Reduced Risk

Genetic variants in the asialoglycoprotein receptor 1 (ASGR1) are associated with a reduced risk of cardiovascular disease (CVD) in humans. However, the underlying molecular mechanism remains elusive. Given the cardiovascular similarities between pigs and humans, we generated ASGR1-deficient pigs using the CRISPR/Cas9 system. These pigs show age-dependent low levels of non-HDL-C under standard diet. When received an atherogenic diet for 6 months, ASGR1-deficient pigs show lower levels of non-HDL-C and less atherosclerotic lesions than that of controls. Furthermore, by analysis of hepatic transcriptome and in vivo cholesterol metabolism, we show that ASGR1 deficiency reduces hepatic de novo cholesterol synthesis by downregulating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and increases cholesterol clearance by upregulating the hepatic low-density lipoprotein receptor (LDLR), which together contribute to the low levels of non-HDL-C. Despite the cardioprotective effect, we unexpectedly observed mild to moderate hepatic injury in ASGR1-deficient pigs, which has not been documented in humans with ASGR1 variants. Thus, targeting ASGR1 might be an effective strategy to reduce hypercholesterolemia and atherosclerosis, whereas further clinical evidence is required to assess its hepatic impact.

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