Biomedical subjects

Patrick Tso

Publications and source records attributed to Patrick Tso.

44 records · Page 3Linked to original sources

PubMed2003

[Role of apolipoprotein A-IV in the regulation of food intake].

Although many exciting functions of Apolipoprotein A-IV(apo-A IV) have been proposed, this review focuses on its unique role in regulating food intake. Apo-A IV is a glycoprotein produced by human intestine and rodent intestine and liver, but the small intestine is the major organ responsible for the circulating apo-A-IV. Our Laboratory recently demonstrated that apo-A IV protein and apo-A IV mRNA were present in rat hypothalamus. Intestinal apo-A IV synthesis is markedly stimulated by fat absorption and the formation of chylomicrons. Intestinal apo-A IV synthesis is also enhanced by the peptide tyrosine-tyrosine. The inhibition of food intake by apo-A IV is mediated centrally. Apo-A IV likely plays a role in the short-term regulation of food intake. Other evidence suggests that apo-A IV may also be involved in the long-term regulation of food intake and body weight. Reduction of apo-A IV in response to lipid feeding in both animal and humans that chronically consume a high-fat diet may explain in part why the chronic ingestion of a high-fat diet predisposes to obesity.

Animals↗

PubMed2002

Intestinal alkaline phosphatase release is not associated with chylomicron formation.

Intestinal alkaline phosphatase (IAP) is one of the major sources of alkaline phosphatase in circulation. It is secreted into the intestinal lumen, serum, and lymph. After the ingestion of lipid, lymphatic alkaline phosphatase secretion increases significantly. We have found that the nonabsorbable fat olestra is unable to stimulate lymphatic alkaline phosphatase secretion. We also found that the hydrophobic surfactant Pluronic L-81, which blocks chylomicron formation, fails to inhibit this increase in lymphatic alkaline phosphatase secretion. These results suggest that it is the lipid uptake into the mucosa and/or reesterification to form triacylglycerols, but not the formation of chylomicrons, that is necessary for the stimulation of the secretion of alkaline phosphatase into the lymph.

Alkaline Phosphatase↗

PubMed2002

Increased neonatal mortality in mice lacking cellular retinol-binding protein II.

Cellular retinol-binding protein II (CRBP II) is a member of the cellular retinol-binding protein family, which is expressed primarily in the small intestine. To investigate the physiological role of CRBP II, the gene encoding CRBP II was inactivated. The saturable component of intestinal retinol uptake is impaired in CRBP II(-/-) mice. The knockout mice, while maintained on a vitamin A-enriched diet, have reduced (40%) hepatic vitamin A stores but grow and reproduce normally. However, reducing maternal dietary vitamin A to marginal levels during the latter half of gestation results in 100% mortality/litter within 24 h after birth in the CRBP II(-/-) line but no mortality in the wild type line. The neonatal mortality in heterozygote offspring of CRBP II(-/-) dams (79 +/- 21% deaths/litter) was increased as compared with the neonatal mortality in heterozygote offspring of wild type dams (29 +/- 25% deaths per litter, p < 0.05). Maternal CRBP II was localized by immunostaining in the placenta at 18 days postcoitum as well as in the small intestine. These studies suggest that both fetal as well as maternal CRBP II are required to ensure adequate delivery of vitamin A to the developing fetus when dietary vitamin A is limiting.

Animals↗

PubMed2002

Intestinal absorption and lymphatic transport of a high gamma-linolenic acid canola oil in lymph fistula Sprague-Dawley rats.

A new canola strain capable of producing >30% gamma-linolenic acid [GLA, 18:3(n-6)] in the seed oil has been developed in our laboratories. This study compares the intestinal absorption and lymphatic transport of this newly developed high GLA content canola oil (HGCO) with traditional GLA-rich borage oil (BO) using a lymph fistula rat model. To assess the extent that 1 mL of GLA in the supplemented oil was absorbed and transported, the fatty acid compositions of triglycerides in mesenteric lymph were compared over a 24-h collection period. The digestion, uptake and lymphatic transport of HGCO and the normal physiologic changes associated with fat absorption (e.g., lymph flow and an increase in lymphatic endogenous lipids outputs, triglycerides, cholesterol and phospholipids) were similar in the HGCO-and the BO-fed rats. The original differences in gamma-linolenic acid content in HGCO and BO were preserved in the fatty acid composition of the rats' lymph lipid. We conclude that the HGCO derived from the genetically modified canola plant is absorbed and transported into lymph similarly to BO.

Animals↗

PubMed2002

Chylomicron components mediate intestinal lipid-induced inhibition of gastric motor function.

Lipid, particularly long-chain triglyceride, initiates feedback regulation of gastrointestinal function. To determine whether the site of action of lipid is pre- or postabsorptive, we investigated the ability of mesenteric lipid-fed lymph to inhibit gastric motor function. Lymph was collected from awake lymph-fistula rats during intestinal infusion with either a glucose-saline maintenance solution or lipid. Intra-arterial injection of lymph collected during intestinal lipid infusion significantly inhibited gastric motility in anesthetized recipient rats compared with injection of equivalent amounts of triglyceride or lymph collected during intestinal infusion of maintenance solution. Lymph collected from rats during lipid infusion with Pluronic L-81 [an inhibitor of chylomicron formation and apolipoprotein (apo) A-IV secretion] compared with lymph injection from donor animals treated with Pluronic L-63 (a noninhibitory control for Pluronic L-81) was significantly less potent. Injection of purified recombinant apo A-IV significantly inhibited gastric motility. Products of lipid digestion and absorption, other than fatty acids or triglyceride, released by the intestine during lipid digestion likely serve as signals to initiate intestinal feedback regulation of gastrointestinal function. Most likely, apo A-IV is one of the signals involved.

Animals↗

PubMed2002

Glutamine promotes triglyceride absorption in a dose-dependent manner.

Dietary proteins may play a role in lipid absorption. Whether amino acids are specifically involved is unknown. We hypothesized that enterally administered L-glutamine (L-Gln) given with a lipid meal increases triglyceride (TG) absorption in rats. Mesenteric lymph fistulae and gastroduodenal feeding tubes were placed in adult male Sprague-Dawley rats. The animals received an enteral bolus of Intralipid (5 ml) followed by enteral infusion of increasing concentrations of L-Gln in saline (0, 85, 170, or 340 mM) or equimolar concentrations of the inactive isomer D-Gln or an essential amino acid mixture without Gln. Lymph was collected continuously for 6 h and analyzed for TG content. Animals infused with 85 mM L-Gln had a 64% increase in total TG output vs. controls (P < 0.05) despite no difference in lymph flow rate. Total TG output for animals infused with 340 mM L-Gln declined by 43% vs. controls (P < 0.05). The effect of Gln in promoting lymphatic fat transport is specific to L-Gln and not shared by D-Gln or an equivalent amino acid mixture. L-Gln is capable of either promoting or impairing lymphatic TG transport in a dose-dependent manner.

Animals↗

PubMed2002

Separation of micelles and vesicles within lumenal aspirates from healthy humans: solubilization of cholesterol after a meal.

Understanding the physico-chemical relationship of lumenal lipids to one another is critical when elucidating the mechanism of components known to impact cholesterol absorption. Presently, there are no studies that describe the proportion of cholesterol carried as micelles or vesicles within human lumenal contents. Part of the reason for the scarceness of data is because of the lack of appropriate methodology required for reproducible sample collection and analysis. Thus, the object of the present studies was to develop a method to measure the amount of cholesterol carried as micelles or vesicles in human lumenal samples. The method includes the collection of lumenal samples from the ligament of Trietz through a Fredrick Miller tube, separation of the aqueous subphase from the nondigested lipids, separation of micelles and vesicles on Sepharose 4B columns within 48 h of collection using elution buffers consisting of the intermicellar bile acid composition, and finally quantitation of cholesterol eluted off of the columns. The distribution of cholesterol between micelles and vesicles obtained under different concentrations of bile acids and various lipids was comparable to results obtained from phase diagrams using the lumenal molar percentages of lipids obtained from the same samples.

Adult↗

PubMed2001

Bile salt-stimulated carboxyl ester lipase influences lipoprotein assembly and secretion in intestine: a process mediated via ceramide hydrolysis.

Bile salt-stimulated carboxyl ester lipase (CEL), also called cholesterol esterase, is one of the major proteins secreted by the pancreas. The physiological role of CEL was originally thought to be its mediation of dietary cholesterol absorption. However, recent studies showed no difference between wild type and CEL knockout mice in the total amount of cholesterol absorbed in a single meal. The current study tests the hypothesis that CEL in the intestinal lumen may influence the type of lipoproteins produced. A lipid emulsion containing 4 mm phospholipid, 13.33 mm [(3)H]triolein, and 2.6 mm [(14)C]cholesterol in 19 mm taurocholate was infused into the duodenum of lymph fistula CEL(+/+) and CEL(-/-) mice at a rate of 0.3 ml/h. Results showed no difference between CEL(+/+) and CEL(-/-) mice in the rate of cholesterol and triglyceride transport from the intestinal lumen to the lymph. However, CEL(-/-) mice produced predominantly smaller lipoproteins, whereas the CEL(+/+) mice produced primarily large chylomicrons and very low density lipoprotein. The proximal intestine of CEL(-/-) mice was also found to possess significantly less ceramide hydrolytic activity than that present in CEL(+/+) mice. By using Caco2 cells grown on Transwell membranes as a model, sphingomyelinase treatment inhibited the secretion of larger chylomicron-like lipoproteins without affecting total cholesterol secretion. In contrast, the addition of CEL to the apical medium increased the amount of large lipoproteins produced and alleviated the inhibition induced by sphingomyelinase. Taken together, this study identified a novel and physiologically significant role for CEL, namely the promotion of large chylomicron production in the intestine. The mechanism appears to be mediated through CEL hydrolysis of ceramide generated during the lipid absorption process.

Amidohydrolases↗