Adaptation to fat markedly increases pancreatic secretory response to intraduodenal fat in rats

Spannagel, Alan W.; Nakano, Ikuta; Tawil, Tippy; Chey, William Y.; Liddle, Rodger A.; Green, G. M.

doi:10.1152/ajpgi.1996.270.1.g128

Cited by 48 publications

(58 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study corroborated the findings of previous investigations showing that infusion of SO or SBTI into the duodenum increases the levels of circulating CCK (42,50), although the basal circulating CCK concentrations observed in the present study were approximately twofold higher than those reported elsewhere. Others reported peak levels after SBTI (28,30) or SO (19) to be Ͻ11 pM compared with 20 pM observed in our laboratory.…”

Section: Discussionsupporting

confidence: 93%

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

Sartor¹,

Shulkes²,

Verberne³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Sartor, Daniela M., Arthur Shulkes, and Anthony J. M. Verberne. An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats. Am J Physiol Regul Integr Comp Physiol 290: R625-R633, 2006. First published October 20, 2005 doi:10.1152/ajpregu.00639.2005.-Ingestion of a meal results in gastrointestinal (GI) hyperemia and is associated with systemic and paracrine release of a number of peptide hormones, including cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT). Systemic administration of CCK octapeptide inhibits a subset of presympathetic neurons of the rostroventrolateral medulla (RVLM) that may be responsible for driving the sympathetic vasomotor tone to the GI viscera. The aim of this study was to determine whether endogenous release of CCK and/or 5-HT also inhibits CCK-sensitive RVLM neurons. The effects of intraduodenal administration of the secretagogues sodium oleate (SO) and soybean trypsin inhibitor (SBTI) on circulating levels of CCK and 5-HT were examined. In separate experiments, the discharge rates of barosensitive, medullospinal, CCK-sensitive RVLM presympathetic vasomotor neurons were recorded after rapid intraduodenal infusion of SO-SBTI or water. Alternatively, animals were pretreated with the CCK 1 receptor antagonists devazepide and lorglumide or the 5-HT 3 antagonist MDL-72222 before SO-SBTI administration. Secretagogue infusion significantly increased the level of circulating CCK, but not 5-HT. SO-SBTI significantly decreased (58%) the neuronal firing rate of CCKsensitive RVLM neurons compared with water (5%). CCK 1 receptor antagonists did not reverse SO-SBTI-induced neuronal inhibition (58%), whereas the 5-HT 3 antagonist significantly attenuated the effect (22%). This study demonstrates a functional relation between a subset of RVLM presympathetic vasomotor neurons and meal-related signals arising from the GI tract. It is likely that endogenously released 5-HT acts in a paracrine fashion on GI 5-HT 3 receptors to initiate reflex inhibition of these neurons, resulting in GI vasodilatation by withdrawal of sympathetic tone. rostroventrolateral medulla; cholecystokinin; devazepide; MDL-72222; 5-hydroxytryptamine GASTROINTESTINAL HYPEREMIA is a physiological consequence of food consumption. Gastrointestinal hormones such as cholecystokinin (CCK) have been implicated in gastrointestinal vasodilatation associated with postprandial increase in splanchnic blood flow. The involvement of the sympathetic vasomotor system in this response is poorly understood. We recently suggested that food-related signals may produce gastrointestinal vasodilatation via a reflex withdrawal of sympathetic vasomotor outflow (39,45). In healthy individuals, the sympathetic nervous system compensates for postprandial splanchnic blood pooling by activating sympathetic vasoconstrictor drive to skeletal muscle resistance vessels in response to baroreceptor unloading. In patients with cardiovascular disease associated with diabetic neuropathy or autonomic dysfunction, poor baroreflex comp...

show abstract

Section: Discussionsupporting

confidence: 93%

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

Sartor¹,

Shulkes²,

Verberne³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…For example, Thomson et al (49) have previously shown that rats fed a high fat diet demonstrated an increase in the height of the villi and a 30% increase in the enterocyte migration rate without affecting the crypt cell production rate. Exposure to a high fat diet also resulted in significant increases in fat absorbability (50), the production and secretion of pancreatic lipases, as well as the ability of isolated rabbit enterocytes to secrete chylomicrons (51)(52)(53). Furthermore, rats fed a high fat diet showed a diminished satiation and reduced sensitivity to leptin (54,55).…”

Section: Discussionmentioning

confidence: 99%

A Predominant Role of Acyl-CoA:monoacylglycerol Acyltransferase-2 in Dietary Fat Absorption Implicated by Tissue Distribution, Subcellular Localization, and Up-regulation by High Fat Diet

Cao

Hawkins

Brozinick

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2) catalyzes the synthesis of diacylglycerol and differs from the MGAT1 and MGAT3 in tissue distribution at the mRNA level. In addition to the small intestine, MGAT2 mRNA is also expressed at high levels in human liver, the lower gastrointestinal tract, and the mouse kidney, but the physiological significance of such expression has not yet been studied. Using an affinitypurified antibody, the present study investigated the expression of murine MGAT2 protein along the intestinal tract, determined its subcellular localization, and studied its regulation by diet and in db/db mouse. Results demonstrate a high level of MGAT2 expression in the small intestine in a proximal-to-distal gradient that correlated well with both MGAT enzyme activity and fat absorption pattern. In contrast, MGAT2 protein was not detectable in other sections of the digestive tract, including stomach, cecum, colon, and rectum, or other mouse tissues such as kidney, liver, and adipocytes. Immunohistological studies provided direct evidence that the enzyme is expressed not only in the villi, but also in the crypt regions of the small intestine, which suggests that MGAT2 expression occurs prior to the maturation of enterocytes. MGAT2 is localized in the endoplasmic reticulum (ER) in both MGAT2-transfected COS-7 and Caco-2 cells, indicating that the ER is the primary site for dietary fat re-synthesis. MGAT2 expression appeared not to be affected by diabetes in the db/db mouse, however, the total intestinal MGAT activity was significantly enhanced. Finally, an up-regulation of both MGAT2 protein expression and MGAT activity was observed in mice fed a high fat diet, implicating a role of MGAT2 in diet-induced obesity. Taken together, our data suggest a predominant role of MGAT2 in dietary fat absorption.In mammals, the small intestine plays a predominant role in the absorption of dietary lipids (mainly triacylglycerol). The absorption of triacylglycerols by the intestinal tract is a complex process that requires several steps, including the hydrolysis of triacylglycerols by pancreatic lipase in the intestinal lumen, the uptake of released 2-monoacylglycerol and fatty acids into enterocytes, and the reconstitution of triacylglycerol in the enterocytes by the monoacylglycerol pathway where 2-monoacylglycerol and fatty acids are utilized to sequentially re-synthesize diacylglycerol and triacylglycerol by acyl-CoA: monoacylglycerol acyltransferase (MGAT) 1 and acyl-CoA:diacylglycerol acyltransferase (DGAT), respectively. Another pathway involved in the triacylglycerol synthesis is the glycerol 3-phosphate pathway, a de novo pathway that is present in most tissues, including small intestine. The pathway begins with acylation of glycerol 3-phosphate with fatty acyl-CoA producing lysophosphatidic acid, followed sequentially by further acylation and dephosphorylation to yield diacylglycerol (1). Both pathways share the final step converting diacylglycerol to triacylglycerol by DGAT. In the small intestinal muc...

show abstract

“…The physiologic importance of this dietary regulation has been shown. The up-regulation of PL enhances the response of cholecystokinin to increased dietary fat by increasing the rate of digestion of triglycerides and the release of FFAs in the proximal small intestine (17). In weanling animals, PL and PLRP1 adapt to increased dietary fat (41-75% of total energy) within 24 h. After 5 d, PL and PLRP1 reach higher steady-state levels of PL activity and synthesis and PL and PLRP1 mRNA (16 -22).…”

mentioning

confidence: 99%

Pancreatic Lipase and Its Related Protein 2 Are Regulated by Dietary Polyunsaturated Fat during the Postnatal Development of Rats

et al. 2004

View full text Add to dashboard Cite

The developmental gene expression of pancreatic lipase (PL) and its related proteins (PLRP1 and PLRP2) is anticoordinate. It is unknown whether dietary fat regulates the expression of these proteins in the preweanling stage. For determining the regulation of development and diet on PL, PLRP1, and PLRP2 as early as the suckling period, pregnant (Sprague-Dawley) rats consumed from day 15 (d15) of pregnancy through d9 of lactation a purified low (11% of energy) safflower oil diet [low-fat (LF)]. From d9 of lactation, dams and their respective pups were fed LF, mediumfat (MF; 40% of energy), or high-fat (HF; 67% of energy) safflower oil diets to d56. Milk fatty acid content had 15-to 100-fold less C:10 and 2.6-to 3.3-fold more C18:2 in MF and HF groups. Diet (LF Ͻ MF ϭ HF; P Ͻ 0.002), postnatal development (d15 Ͻ d21 Ͻ d28 ϭ d56; P Ͻ 0.001), and interaction of diet ϫ development significantly affected PL activity starting as early as d15. PL mRNA levels showed a parallel effect of diet (LF Ͻ HF ϭ MF; P Ͻ 0.013) and development (P Ͻ 0.001). Both PLRP1 and PLRP2 mRNA levels were significantly affected by development (P Ͻ 0.001) and had an anticoordinate pattern compared with PL expression (d15 Ͼ d21 Ͼ d28). Reported for the first time is the significant down-regulation of PLRP2 mRNA levels by high polyunsaturated fat in suckling (d15) Dietary fat provides the major energy (~50% calories) during infancy in breast milk and formulas (1). During the past decade, special attention has been given to the type of fat necessary for normal infant development, especially to longchain polyunsaturated fatty acids (PUFA). PUFA derived from essential fatty acids (C18:2, linoleic acid, and C18:3␣-linolenic) play a key role in brain and normal retinal development (2).Fat digestion and absorption in the infant and premature neonate depend on the developmental pattern of lipases (3).The digestive system continues to develop after birth in infants, and especially so in premature neonates, influencing their ability to digest fat. Gastric lipase, which starts the digestion of dietary fat and accounts for 10 -30% of fat digestion (4), pancreatic colipase-dependent lipase, and milk bile saltstimulated lipase all have potential roles in digestion of milk fat in the neonate (3). Pancreatic lipase-related protein 2 (PLRP2) may play a role in neonatal fat digestion as well (5). Although the pancreatic lipase levels in the newborn and even more so in the premature infant are low, the digestion of milk fat depends on these four lipases with unique and only partially overlapping functions (5-7).The exocrine pancreas synthesizes and secretes pancreatic lipase and two pancreatic lipase-related proteins; PLRP1 and PLRP2. PL and its related proteins have been identified in humans and rats. The PLRP1 is highly homologous to PL with conserved serine and histidine residues in the active site (8,9); however, this protein does not exhibit colipasedependent lipolytic activity when its full-length cDNA is expressed in COS or Sf9 cells (8,9). Although PLRP1 i...

show abstract

Adaptation to fat markedly increases pancreatic secretory response to intraduodenal fat in rats

Cited by 48 publications

References 0 publications

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

A Predominant Role of Acyl-CoA:monoacylglycerol Acyltransferase-2 in Dietary Fat Absorption Implicated by Tissue Distribution, Subcellular Localization, and Up-regulation by High Fat Diet

Pancreatic Lipase and Its Related Protein 2 Are Regulated by Dietary Polyunsaturated Fat during the Postnatal Development of Rats

Contact Info

Product

Resources

About