FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2153644531> ?p ?o ?g. }

• W2153644531 endingPage "3523" @default.
• W2153644531 startingPage "3516" @default.
• W2153644531 abstract "The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r =−0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state. The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r =−0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state. The insulin-resistance state and type 2 diabetes mellitus (T2DM) are closely related with an increase in cardiovascular disease. Factors conditioning this increase in cardiovascular disease include metabolic dyslipidemia associated with insulin resistance. It has recently been suggested that the overproduction of intestinally derived apolipoprotein (apo)B48-containing lipoproteins may contribute greatly to the dyslipidemia found in both the fasting and postprandial states in insulin resistance (1Haidari M. Leung N. Mahbub F. Uffelman K.D. Kohen-Avramoglu R. Lewis G.F. Adeli K. Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. Evidence that chronic fructose feeding in the hamster is accompanied by enhanced intestinal de novo lipogenesis and ApoB48-containing lipoprotein overproduction.J. Biol. Chem. 2002; 277: 31646-31655Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 2Guo Q. Avramoglu R.K. Adeli K. Intestinal assembly and secretion of highly dense/lipid-poor apolipoprotein B48-containing lipoprotein particles in the fasting state: evidence for induction by insulin resistance and exogenous fatty acids.Metabolism. 2005; 54: 689-697Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 3Lewis G.F. Uffelman K. Naples M. Szeto L. Haidari M. Adeli K. Intestinal lipoprotein overproduction, a newly recognized component of insulin resistance, is ameliorated by the insulin sensitizer rosiglitazone: studies in the fructose-fed Syrian golden hamster.Endocrinology. 2005; 146: 247-255Crossref PubMed Scopus (75) Google Scholar). However, the underlying mechanisms are still not fully understood. Most studies undertaken in this area have been carried out in the postprandial state (3Lewis G.F. Uffelman K. Naples M. Szeto L. Haidari M. Adeli K. Intestinal lipoprotein overproduction, a newly recognized component of insulin resistance, is ameliorated by the insulin sensitizer rosiglitazone: studies in the fructose-fed Syrian golden hamster.Endocrinology. 2005; 146: 247-255Crossref PubMed Scopus (75) Google Scholar, 4Risser T.R. Reaven G.M. Reaven E.P. Intestinal contribution to secretion of very low density lipoproteins into plasma.Am. J. Physiol. 1978; 234: E277-E281PubMed Google Scholar). The intestine maintains a basal production of apoB48, even in fasting states, synthesizing small triglyceride-rich lipoprotein (TRL) particles (4Risser T.R. Reaven G.M. Reaven E.P. Intestinal contribution to secretion of very low density lipoproteins into plasma.Am. J. Physiol. 1978; 234: E277-E281PubMed Google Scholar, 5Ockner R.K. Hughes F.B. Isselbacher K.J. Very low density lipoproteins in intestinal lymph: origin, composition, and role in lipid transport in the fasting state.J. Clin. Invest. 1969; 48: 2079-2088Crossref PubMed Scopus (111) Google Scholar). Animal studies have shown that the contribution of intestinal lipoproteins to the total fasting plasma triglycerides is from 10% to 20% (4Risser T.R. Reaven G.M. Reaven E.P. Intestinal contribution to secretion of very low density lipoproteins into plasma.Am. J. Physiol. 1978; 234: E277-E281PubMed Google Scholar, 5Ockner R.K. Hughes F.B. Isselbacher K.J. Very low density lipoproteins in intestinal lymph: origin, composition, and role in lipid transport in the fasting state.J. Clin. Invest. 1969; 48: 2079-2088Crossref PubMed Scopus (111) Google Scholar), increasing in the case of diabetes (4Risser T.R. Reaven G.M. Reaven E.P. Intestinal contribution to secretion of very low density lipoproteins into plasma.Am. J. Physiol. 1978; 234: E277-E281PubMed Google Scholar, 6Curtin A. Deegan P. Owens D. Collins P. Johnson A. Tomkin G.H. Elevated triglyceride-rich lipoproteins in diabetes. A study of apolipoprotein B-48.Acta Diabetol. 1996; 33: 205-210Crossref PubMed Scopus (83) Google Scholar, 7Haffner S.M. Foster D.M. Kushwaha R.S. Hazzard W.R. Retarded chylomicron apolipoprotein-B catabolism in type 2 (non-insulin-dependent) diabetic subjects with lipaemia.Diabetologia. 1984; 26: 349-354Crossref PubMed Scopus (26) Google Scholar). Fructose-fed hamsters experience an increase in the assembly and secretion of apoB48-containing lipoproteins in insulin-resistant states (2Guo Q. Avramoglu R.K. Adeli K. Intestinal assembly and secretion of highly dense/lipid-poor apolipoprotein B48-containing lipoprotein particles in the fasting state: evidence for induction by insulin resistance and exogenous fatty acids.Metabolism. 2005; 54: 689-697Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar). Duez et al. showed that the production of chylomicrons (CM) was upregulated in humans with insulin resistance (8Duez H. Lamarche B. Valéro R. Pavlic M. Proctor S. Xiao C. Szeto L. Patterson B.W. Lewis G.F. Both intestinal and hepatic lipoprotein production are stimulated by an acute elevation of plasma free fatty acids in humans.Circulation. 2008; 117: 2369-2376Crossref PubMed Scopus (96) Google Scholar). Studies undertaken in fructose-fed, insulin-resistant Syrian golden hamsters in both the fasted and fed states found that, in these insulin-resistant animals, the increased production of small TRL was greater in the fasted state than the fed state (1Haidari M. Leung N. Mahbub F. Uffelman K.D. Kohen-Avramoglu R. Lewis G.F. Adeli K. Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. Evidence that chronic fructose feeding in the hamster is accompanied by enhanced intestinal de novo lipogenesis and ApoB48-containing lipoprotein overproduction.J. Biol. Chem. 2002; 277: 31646-31655Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar). Nevertheless, caution should be exercised when extrapolating results from experimental animal models to humans, due to the differences between species. Advances in the understanding of TRL assembly have shown the roles of apoA-IV and the microsomal triglyceride transfer protein (MTP) in the regulation of the synthesis and secretion of TRL. MTP is responsible for the lipidation of the chylomicron particle and apoA-IV has an important role in enhancing the secretion of chylomicrons and associated lipids in newborn enterocytes (9Black D.D. Development and physiological regulation of intestinal lipid absorption. I. Development of intestinal lipid absorption: cellular events in chylomicron assembly and secretion.Am. J. Physiol. Gastrointest. Liver Physiol. 2007; 293: G519-G524Crossref PubMed Scopus (91) Google Scholar, 10Lu S. Yao Y. Cheng X. Mitchell S. Leng S. Meng S. Gallagher J.W. Shelness G.S. Morris G.S. Mahan J. et al.Overexpression of apolipoprotein A-IV enhances lipid secretion in IPEC-1 cells by increasing chylomicron size.J. Biol. Chem. 2006; 281: 3473-3483Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar, 11Lu S. Yao Y. Meng S. Cheng X. Black D.D. Overexpression of apolipoprotein A-IV enhances lipid transport in newborn swine intestinal epithelial cells.J. Biol. Chem. 2002; 277: 31929-31937Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar). Recently, it has been shown that angiopoietin-like protein 4 (ANGPTL4), an inhibitor of lipoprotein lipase activity, is a regulator of glucose homeostasis, lipid metabolism, and insulin sensitivity and is also involved in the metabolism of TRL (12Ge H. Yang G. Yu X. Pourbahrami T. Li C. Oligomerization state-dependent hyperlipidemic effect of angiopoietin-like protein 4.J. Lipid Res. 2004; 45: 2071-2079Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar). To date, most studies have addressed the clearing processes of these apoB48-containing intestinal lipoproteins and their degree of production (7Haffner S.M. Foster D.M. Kushwaha R.S. Hazzard W.R. Retarded chylomicron apolipoprotein-B catabolism in type 2 (non-insulin-dependent) diabetic subjects with lipaemia.Diabetologia. 1984; 26: 349-354Crossref PubMed Scopus (26) Google Scholar). However, as far as we are aware, no study has yet attempted to determine whether there is an alteration in the lipid content in the human gut associated with the dyslipidemia found in persons with T2DM. The aim of this study was to determine whether there is an alteration in the lipid content in the jejunum of persons with morbid obesity, with or without T2DM, and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of TRL. The study was undertaken in 27 morbidly obese persons who underwent a Roux-en-Y gastric bypass, 12 of whom had T2DM. Eight morbidly obese patients with T2DM were receiving metformin. None of the morbidly obese persons with T2DM was receiving insulin therapy, nor were any of the morbidly obese persons receiving estrogens, statins, or other cholesterol-lowering agents. All the morbidly obese persons followed a similar low-calorie diet for one week prior to surgery, independently of their states of obesity and insulin resistance (630 Kcal/day, Optisource, Novartis Consumer Health S.A.). Blood samples were drawn on the day before surgery after a 10–12 h fast. The plasma was separated and immediately frozen at –80°C. An unfrozen aliquot of plasma was used to isolate the lipoproteins. Jejunum samples were obtained from the morbidly obese persons during gastric bypass, 40 cm from the ligament of Treitz. Samples were washed in physiological saline, fractionated, and then prepared for histochemical and immunohistochemical analysis, quantification of the jejunal triglycerides, and mRNA extraction. All the participants gave their informed consent, and the study was reviewed and approved by the Ethics and Research Committee of Carlos Haya Regional University Hospital (Malaga, Spain). For histochemical and immunohistochemical analysis, jejunum samples were frozen in liquid nitrogen. From each tissue, serial 4 μm transverse sections were cut using a cryostat at –20°C, placed in an Oil Red-O staining solution, and briefly washed. A counterstain in Harris hematoxylin was performed. For immunohistochemical analysis, all steps were performed at room temperature in a humid chamber. Sections were first fixed for 30 min with formol, and then washed in 0.1M phosphate buffered saline (PBS). The sections were then incubated for 30 min with 3% H2O2/methanol with PBS to inactivate endogenous peroxidase. After washing, antigen retrieval procedures were performed. After several washes with PBS, the sections were exposed to the primary antibodies overnight (ab7616, goat anti-human apoB) (Santa Cruz Biotechnology, Santa Cruz, CA). Washed sections were then incubated with the appropriate biotinylated secondary antibodies for 1 h [biotin-conjugated rabbit anti-goat immunoglobulin (Ig) (DakoCytomation, Glostrup, Denmark)]. The samples were washed with PBS, and ExtrAvidin-peroxidase (Sigma) was applied. The visualization of the signal was done by using 3,3′-diaminobenzidine substrate kit (Sigma). All the antibodies were used according to the manufacturer's instructions. Omission of the primary antibody resulted in no detectable staining. These sections were counterstained with hematoxylin. The slides were viewed using an Olympus BX41 microscope (Olympus, UK) with an Olympus DP70 digital camera (Olympus, UK). ImageJ version 1.32j software was used to analyze the relative quantity of apoB in the lamina propria of the samples. A sample of full-thickness jejunum was taken to analyze the triglyceride content. Briefly, lipids were extracted with chloroform-methanol 2:1 (v/v) after sample homogenization. The organic phase was collected and evaporated under a current of nitrogen. The extracts were resuspended in isopropanol, and the concentration of triglycerides was determined by using commercial kits (Randox Laboratories, Antrium, UK) (13Gil-Villarino A. Garcia-Fuentes E. Zafra F. Garcia-Peregrin E. Production of a rapid hypercholesterolemia in young chick by feeding coconut oil from two different sources and fatty acid composition.Nutr. Res. 1998; 18: 1273-1285Crossref Scopus (10) Google Scholar). The results were expressed as mmol of triglycerides/g of jejunal tissue (jejunal triglycerides). The biopsy samples were washed in physiological saline, the mucosa was scraped, and samples were immediately frozen in liquid nitrogen. Biopsy samples were maintained at –80°C until analysis. Total RNA isolation was obtained using RNeasy Lipid Tissue Mini Kit (Qiagen, Germany), as described (14Macias-Gonzalez M. Moreno-Santos I. García-Almeida J.M. Tinahones F.J. Garcia-Fuentes E. PPARgamma2 protects against obesity by means of a mechanism that mediates insulin resistance.Eur. J. Clin. Invest. 2009; 39: 972-979Crossref PubMed Scopus (18) Google Scholar). First strand cDNA was synthesized by retrotranscription using the M-MLV retrotranscriptase (Sigma). Gene expression levels were analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) using a DNA Engine Opticon® System (MJ Research, Waltham, MA). Primers for the PCR reaction were designed based on NCBI database sequences and obtained from Proligo (Sigma) (18s: NM_014473.2; apoA-IV: NM_000482.3; ANGPTL4: NM_139314; and MTP: NM_000253). Calculation of relative expression levels of the different transcripts was performed based on the cycle threshold (CT) method. Thus, the CT value for each sample was calculated using the DNA Engine Opticon® System software with an automatic fluorescence threshold setting. Reactions were done in triplicate. Standard curves were constructed for the studied genes and 18S (internal control) by plotting values of CT (the cycle in which the fluorescence signal exceeds background) versus logcDNAinput (in nanograms). CT values from each experimental sample were then used to calculate the amount of apoA-IV, ANGPTL4, and MTP. The gene expression of cells was expressed as the percentage of relative gene expression referred to the internal calibrator included in each experiment. Lipoproteins were separated from plasma by ultracentrifugation. Briefly, the chylomicron fraction was separated from the plasma by flotation at 35,000 rpm in a 45° rotor (Beckman TLA 100.3) (15Cardona F. Tinahones F.J. Collantes E. Escudero A. García-Fuentes E. Soriguer F.J. The elevated prevalence of apolipoprotein E2 in patients with gout is associated with reduced renal excretion of urates.Rheumatology (Oxford). 2003; 42: 468-472PubMed Google Scholar). Then, the very low-density lipoprotein (VLDL) fraction was separated from the plasma by flotation at 55,000 rpm in a 45° rotor (Beckman TLA 100.3). After separation of the VLDL, the density of the infranatant was adjusted to 1.30 g/ml, separating the rest of the lipoproteins, intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) by density gradient centrifugation (16García-Fuentes E. Gil-Villarino A. Zafra M.F. García-Peregrín E. Hypocholesterolemic activity of dipyridamole: effects on chick plasma and lipoprotein composition and arachidonic acid levels.Environ. Toxicol. Pharmacol. 2000; 8: 261-266Crossref PubMed Scopus (9) Google Scholar). The concentrations of cholesterol and triglycerides were measured in each fraction. ApoB48 in plasma chylomicron was analyzed on a 5% sodium dodecyl sulfate (SDS) polyacrylamide gel as described (17Verseyden C. Meijssen S. Castro Cabezas M. Postprandial changes of apoB-100 and apoB-48 in TG rich lipoproteins in familial combined hyperlipidemia.J. Lipid Res. 2002; 43: 274-280Abstract Full Text Full Text PDF PubMed Google Scholar). Briefly, the chylomicron fractions were isolated from the same amount of plasma in each patient. The chylomicron fraction was delipidated with methanol/diethylether solvent system by gently dipping the sample into 4 ml methanol. A volume of 4 ml ice-cold diethylether was added. The delipidation cocktail was mixed and centrifuged for 48 min at 2,500 g at 4°C. The supernatant was removed, and 4 ml of ice-cold diethylether was added. The sample was mixed and again centrifuged for 32 min at 2,500 g at 4°C, and the supernatant was again removed. The sample was dried by lyophilization and dissolved in sample buffer for 1 h at room temperature and then heated at 80°C for 15 min. Samples and a protein standard were loaded onto the gel, followed by electrophoretic transfer to a polyvinylidene difluoride membrane at 15 V for 1 h. The membranes were blocked in Protein-Free Tween 20 Blocking Buffer (Pierce, Rockford, IL) overnight at 4°C. After washing with PBS plus 0.05% Tween 20, membranes were incubated with a polyclonal anti apoB (Santa Cruz Biotechnology) at a dilution of 1:200 for 1 h at room temperature. This antibody is an affinity-purified goat polyclonal antibody used in other studies to identify apoB48 (18Vine D.F. Takechi R. Russell J.C. Proctor S.D. Impaired postprandial apolipoprotein-B48 metabolism in the obese, insulin-resistant JCR:LA-cp rat: increased atherogenicity for the metabolic syndrome.Atherosclerosis. 2007; 190: 282-290Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar). Membranes were washed and incubated with HRP-conjugated donkey anti-goat IgG antibody (Santa Cruz Biotechnology) at a dilution of 1:2000 for 1 h at room temperature. The proteins were visualized with SuperSignal® West Pico Chemiluminescent Substrate (Pierce, Rockford, IL) in an ImageQuant LAS 4000 with the ImageQuant TL software (GE Healthcare, Uppsala, Sweden). Plasma biochemical variables were measured in duplicate. Glucose, cholesterol, triglycerides (Randox Laboratories, Antrium, UK) and free fatty acids (Wako Bioproducts, Richmond, VA) were determined by standard enzymatic methods. The insulin was analyzed by an immunoradiometric assay (BioSource International, Camarillo, CA). ApoB48 was analyzed by enzyme immunoassay (ELISA) (Shibayagi, Japan). Cross-reaction with human apoB-100 was less than the lower detection limit. The intra- and inter-assay CV was 3.5% and 5.7%, respectively. The sensitivity of the technique was 2.5 ng/ml. ApoA-IV was analyzed by ELISA (Millipore Corporation, Billerica, MA). The intra- and inter-assay CV was 4.6% and 12.2%, respectively. The sensitivity of the technique was 0.078 μg/ml. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting insulin and glucose with the following equation: HOMA-IR = fasting insulin (μIU/ml) × fasting glucose (mmol/l) / 22.5 The statistical analysis was done with SPSS version 11.5 for Windows (SPSS, Chicago, IL). Comparison between the results of the different groups was made with the Mann-Whitney test. The Spearman correlation coefficient was calculated to estimate the linear correlations between variables. Multiple linear regressions were used to determine the association between variables. Values were considered statistically significant when P ≤ 0.05. The results are given as the mean ± SD. No significant differences were found between the two groups of morbidly obese persons (with or without T2DM) in the anthropometric variables studied (age, weight, BMI, and waist and hip circumferences) (Table 1). Plasma glucose, insulin, triglycerides, apoB48 and apoA-IV levels, HOMA-IR, chylomicron cholesterol, and triglycerides were significantly higher in the morbidly obese persons with T2DM (Table 1). The results of serum apoB48 by ELISA were confirmed by a Western blot of the proteins isolated from plasma chylomicrons (Fig. 1).TABLE 1.Clinical and biochemical variables in the morbidly obese personsVariableMorbidly Obese Persons without T2DMMorbidly Obese Persons with T2DMN (men/women)14 (4/10)13 (3/10)Age (years)44.4 ± 7.748.5 ± 9.0Weight (kg)143.3 ± 22.2139.4 ± 24.3Body mass index (kg/m )55.0 ± 7.850.5 ± 6.2Waist (cm)140.1 ± 14.8142.3 ± 12.2Hip (cm)154.1 ± 18.5141.4 ± 16.2Glucose (mmol/l)5.66 ± 0.479.61 ± 2.60cP < 0.001.Insulin (pmol/l)172.3 ± 84.7234.6 ± 114.1aP < 0.05.Free fatty acids (mmol/l)0.680 ± 0.2370.751 ± 0.142Cholesterol (mmol/l)5.55 ± 1.555.64 ± 1.06HDL cholesterol (mmol/l)1.23 ± 0.311.01 ± 0.23LDL cholesterol (mmol/l)3.25 ± 1.323.22 ± 0.34IDL cholesterol (mmol/l)0.20 ± 0.060.16 ± 0.06VLDL cholesterol (mmol/l)0.53 ± 0.270.65 ± 0.31CM cholesterol (mmol/l)0.34 ± 0.240.60 ± 0.22aP < 0.05.Triglycerides (mmol/l)1.46 ± 0.433.35 ± 0.91cP < 0.001.HDL triglycerides (mmol/l)0.25 ± 0.080.29 ± 0.06LDL triglycerides (mmol/l)0.31 ± 0.070.32 ± 0.07IDL triglycerides (mmol/l)0.12 ± 0.030.10 ± 0.03VLDL triglycerides (mmol/l)0.45 ± 0.150.68 ± 0.35CM triglycerides (mmol/l)0.33 ± 0.131.96 ± 0.25bP < 0.01.ApoB48 (μg/ml)8.64 ± 4.9643.6 ± 16.3bP < 0.01.ApoB-100 (mg/dl)127.0 ± 27.8131.2 ± 20.1ApoA-IV (mg/dl)20.2 ± 7.327.4 ± 3.7cP < 0.001.HOMA-IR5.9 ± 2.714.2 ± 7.7bP < 0.01.Jejunal triglycerides (mmol/g)7.12 ± 3.502.84 ± 0.76cP < 0.001.Jejunal apoB signal intensity155.6 ± 8.1140.8 ± 7.5bP < 0.01.Data are expressed as mean ± SD. Results adjusted for age and body mass index. Apo, apolipoprotein; CM, chylomicron; HDL, high density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; IDL, intermediate density lipoprotein; LDL, low density lipoprotein; T2DM, type 2 diabetes mellitus; VLDL, very low density lipoprotein.a P < 0.05.b P < 0.01.c P < 0.001. Open table in a new tab Data are expressed as mean ± SD. Results adjusted for age and body mass index. Apo, apolipoprotein; CM, chylomicron; HDL, high density lipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; IDL, intermediate density lipoprotein; LDL, low density lipoprotein; T2DM, type 2 diabetes mellitus; VLDL, very low density lipoprotein. The jejunal triglyceride content differed significantly between the two groups of morbidly obese persons (P = 0.012) (Table 1). The lower content in the morbidly obese persons with T2DM was corroborated by the reduction in neutral lipids seen on Oil Red-O staining of the jejunum [T2DM versus non-T2DM (Fig. 2A, B); and T2DM versus non-T2DM (Fig. 2C, D)]. suggests that most of the triglycerides are not inside enterocytes. To determine whether these lipids were in the form of lipoproteins, we performed an immunohistochemical stain with an antibody against apoB. As can be seen from Table 1 and Fig. 2 [morbidly obese persons with T2DM (Fig. 2E, G) versus morbidly obese persons without T2DM (Fig. 2F, H)], the signal obtained in the morbidly obese persons with T2DM was lower than that in the persons without T2DM (P = 0.008). Both the apoB signal and the neutral lipids were mainly located in the lamina propria of the jejunal samples. Immunohistochemical analysis showed a slight, nonsignificant increase in the signal obtained in enterocyte apoB staining in the morbidly obese persons with T2DM (118.8 ± 8.7 versus 110.4 ± 4.5, P = 0.101). No significant differences were found between morbidly obese persons with T2DM according to whether or not they were on metformin (data not shown). In the morbidly obese persons with T2DM, the apoA-IV mRNA expression was significantly greater (P = 0.036) (Fig. 3A) and ANGPTL4 mRNA expression significantly lower (P = 0.043) (Fig. 3B) than these expressions in the morbidly obese patients without T2DM. No significant differences were detected between the two groups of morbidly obese patients in MTP mRNA expression (P = 0.456) (Fig. 3C). No significant differences were found between the morbidly obese persons with T2DM according to whether or not they were on metformin (data not shown). Significant associations of plasma apoB48, apoA-IV, and chylomicron triglycerides with plasma variables and mRNA expression are shown in Table 2. There were no significant correlations with the remaining variables (data not shown).TABLE 2Significant correlations (P) between plasma levels of apoA-IV, apoB48, CM triglycerides, jejunal triglyceride content, and jejunal apoB signal intensity and other anthropometric and biochemical variablesVariableApoA-IVApoB48CM TriglyceridesJejunal TriglyceridesJejunal ApoBSignal IntensityGlucose0.495 (0.001)0.596 (0.020)0.875 (<0.001)−0.786 (<0.001)−0.675 (0.006)Insulin0.354 (0.009)0.561 (0.030)0.521 (0.046)−0.632 (0.011)−0.625 (0.013)CM cholesterolNS0.514 (0.040)0.670 (0.009)−0.596 (0.025)−0.771 (0.001)Triglycerides0.513 (0.030)0.5974(0.020)0.836 (<0.001)−0.692 (0.003)−0.661 (0.005)CM triglyceridesNS0.774 (<0.001)–−0.791 (<0.001)−0.724 (0.002)ApoB480.471 (0.023)–0.774 (<0.001)−0.768 (0.001)−0.674 (0.004)HOMA-IR0.560 (<0.001)0.688 (0.003)0.700 (0.003)−0.774 (0.001)−0.747 (0.001)Jejunal triglyceridesNS−0.768 (0.001)−0.791 (<0.001)–0.776 (<0.001)ApoA-IV mRNANSNSNS−0.587 (0.027)NSANGPTL4 mRNANSNSNSNSNSMTP mRNANS−0.539 (0.038)−0.564 (0.028)NSNSANGPTL4, angiopoietin-like protein 4; apo, apolipoprotein; CM, chylomicron; HOMA-IR, homeostatic model assessment of insulin resistance; MTP, microsomal triglyceride transfer protein; NS, not significant. Open table in a new tab ANGPTL4, angiopoietin-like protein 4; apo, apolipoprotein; CM, chylomicron; HOMA-IR, homeostatic model assessment of insulin resistance; MTP, microsomal triglyceride transfer protein; NS, not significant. ApoA-IV mRNA expression correlated with weight (r =−0.513, P = 0.013) and the jejunal triglyceride content (r =−0.587, P = 0.027). ANGPTL4 mRNA expression correlated with glucose (r =−0.676, P < 0.001), waist (r = 0.583, P = 0.011), and hip circumference (r = 0.573, P = 0.013). MTP mRNA expression also correlated with apoB (r = 0.558, P = 0.047), apoB48 (r =−0.539, P = 0.038), and chylomicron triglycerides (r =−0.564, P = 0.028). Significant correlations were found between the jejunal triglyceride content and jejunal apoB signal intensity and the plasma levels of glucose, insulin, triglycerides, chylomicron triglycerides, apoB48, and HOMA-IR (Table 2). Jejunal triglycerides also correlated with apoA-IV mRNA expression (Table 2). The variables that best explained the jejunal triglyceride content in a multiple linear regression model were the HOMA-IR and the apoA-IV mRNA expression (Table 3).TABLE 3Multiple linear regression analysis of jejunal triglyceride contentVariableB coefficientSE Bβ95% CIPConstant4.6863.957(−4.670) – (14.042)0.275Age0.0340.0650.115(−0.118) – (0.187)0.611Sex0.8531.6200.113(−2.977) – (4.683)0.615MTP mRNA0.0200.0130.335(−0.011) – (0.050)0.166ANGPTL4 mRNA−0.0010.006−0.024(−0.014) – (0.013)0.919ApoA-IV mRNA−0.0220.009−0.532(−0.043) – (−0.001)0.041HOMA-IR−0.3490.129−0.586(−0.654) – (−0.045)0.030R2 for the model: 0.712. Sex: men = 1, women = 2. ANGPTL4, angiopoietin-like protein 4; apo, apolipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; MTP, microsomal triglyceride transfer protein; SE, standard error. Open table in a new tab R2 for the model: 0.712. Sex: men = 1, women = 2. ANGPTL4, angiopoietin-like protein 4; apo, apolipoprotein; HOMA-IR, homeostatic model assessment of insulin resistance; MTP, microsomal triglyceride transfer protein; SE, standard error. This study shows that the lipid content of the jejunum in morbidly obese persons varies significantly between patients with or without T2DM, and it is inversely related with the plasma levels of chyl" @default.
• W2153644531 created "2016-06-24" @default.
• W2153644531 creator A5007499817 @default.
• W2153644531 creator A5015390601 @default.
• W2153644531 creator A5045326174 @default.
• W2153644531 creator A5048380224 @default.
• W2153644531 creator A5064099245 @default.
• W2153644531 creator A5065430380 @default.
• W2153644531 creator A5074701779 @default.
• W2153644531 creator A5081374906 @default.
• W2153644531 creator A5091618774 @default.
• W2153644531 creator A5091831912 @default.
• W2153644531 date "2010-12-01" @default.
• W2153644531 modified "2023-10-18" @default.
• W2153644531 title "Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus" @default.
• W2153644531 cites W1852041846 @default.
• W2153644531 cites W2000514316 @default.
• W2153644531 cites W2004793722 @default.
• W2153644531 cites W2007032642 @default.
• W2153644531 cites W2020049282 @default.
• W2153644531 cites W2022458426 @default.
• W2153644531 cites W2022687039 @default.
• W2153644531 cites W2025050749 @default.
• W2153644531 cites W2033662263 @default.
• W2153644531 cites W2035433195 @default.
• W2153644531 cites W2042381594 @default.
• W2153644531 cites W2045893219 @default.
• W2153644531 cites W2048580400 @default.
• W2153644531 cites W2056303106 @default.
• W2153644531 cites W2062925748 @default.
• W2153644531 cites W2068021492 @default.
• W2153644531 cites W2079543195 @default.
• W2153644531 cites W2082378150 @default.
• W2153644531 cites W2082707171 @default.
• W2153644531 cites W2083775524 @default.
• W2153644531 cites W2091539862 @default.
• W2153644531 cites W2100270286 @default.
• W2153644531 cites W2108629423 @default.
• W2153644531 cites W2111466539 @default.
• W2153644531 cites W2115912100 @default.
• W2153644531 cites W2116463176 @default.
• W2153644531 cites W2127136426 @default.
• W2153644531 cites W2129606778 @default.
• W2153644531 cites W2136750026 @default.
• W2153644531 cites W2139422917 @default.
• W2153644531 cites W2142518843 @default.
• W2153644531 cites W2143440758 @default.
• W2153644531 cites W2158210244 @default.
• W2153644531 cites W2161343289 @default.
• W2153644531 cites W2340094823 @default.
• W2153644531 cites W2922316283 @default.
• W2153644531 doi "https://doi.org/10.1194/jlr.m007815" @default.
• W2153644531 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2975724" @default.
• W2153644531 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20855567" @default.
• W2153644531 hasPublicationYear "2010" @default.
• W2153644531 type Work @default.
• W2153644531 sameAs 2153644531 @default.
• W2153644531 citedByCount "17" @default.
• W2153644531 countsByYear W21536445312012 @default.
• W2153644531 countsByYear W21536445312013 @default.
• W2153644531 countsByYear W21536445312015 @default.
• W2153644531 countsByYear W21536445312017 @default.
• W2153644531 countsByYear W21536445312020 @default.
• W2153644531 countsByYear W21536445312021 @default.
• W2153644531 countsByYear W21536445312022 @default.
• W2153644531 crossrefType "journal-article" @default.
• W2153644531 hasAuthorship W2153644531A5007499817 @default.
• W2153644531 hasAuthorship W2153644531A5015390601 @default.
• W2153644531 hasAuthorship W2153644531A5045326174 @default.
• W2153644531 hasAuthorship W2153644531A5048380224 @default.
• W2153644531 hasAuthorship W2153644531A5064099245 @default.
• W2153644531 hasAuthorship W2153644531A5065430380 @default.
• W2153644531 hasAuthorship W2153644531A5074701779 @default.
• W2153644531 hasAuthorship W2153644531A5081374906 @default.
• W2153644531 hasAuthorship W2153644531A5091618774 @default.
• W2153644531 hasAuthorship W2153644531A5091831912 @default.
• W2153644531 hasBestOaLocation W21536445311 @default.
• W2153644531 hasConcept C126322002 @default.
• W2153644531 hasConcept C134018914 @default.
• W2153644531 hasConcept C2778163477 @default.
• W2153644531 hasConcept C2778913445 @default.
• W2153644531 hasConcept C2910068830 @default.
• W2153644531 hasConcept C3019948525 @default.
• W2153644531 hasConcept C511355011 @default.
• W2153644531 hasConcept C544821477 @default.
• W2153644531 hasConcept C555293320 @default.
• W2153644531 hasConcept C71924100 @default.
• W2153644531 hasConceptScore W2153644531C126322002 @default.
• W2153644531 hasConceptScore W2153644531C134018914 @default.
• W2153644531 hasConceptScore W2153644531C2778163477 @default.
• W2153644531 hasConceptScore W2153644531C2778913445 @default.
• W2153644531 hasConceptScore W2153644531C2910068830 @default.
• W2153644531 hasConceptScore W2153644531C3019948525 @default.
• W2153644531 hasConceptScore W2153644531C511355011 @default.
• W2153644531 hasConceptScore W2153644531C544821477 @default.
• W2153644531 hasConceptScore W2153644531C555293320 @default.
• W2153644531 hasConceptScore W2153644531C71924100 @default.
• W2153644531 hasIssue "12" @default.

• next