Elevation of plasma neurotensin during lipid perfusion of rat small intestine

Ferris, Craig F.; Hammer, Robert A.; Leeman, Susan E.

doi:10.1016/0196-9781(81)90042-5

Cited by 80 publications

(22 citation statements)

References 12 publications

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“…These substances, which resemble the C-terminal region of NT, have not been characterized chromatographically yet. Although the data presented here did not demonstrate an increase in either NT itself or in C-terminal immunoreactivity (HC-8) in peripheral plasma, such an elevation may have occurred in the portal circulation (21) or in the peripheral circulation at times other than those at which samples were collected.…”

Section: Discussionmentioning

confidence: 64%

Elevation of Plasma Neurotensinlike Immunoreactivity after a Meal

Hammer¹,

Carraway²,

Leeman³

1982

J. Clin. Invest.

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A B S T R A C T The detection of an elevation in neurotensinlike immunoreactivity in peripheral plasma for several hours after a meal has been confirmed and shown to be primarily due to the presence of aminoterminal fragments of neurotensin (NT) rather than to NT itself. We have developed a procedure to separate and characterize these N-terminal cross-reacting substances, and to estimate the contributions of these constitutents to plasma neurotensinlike immunoreactivity. Gel chromatography of pooled plasma extracts on Sephadex G-25 followed by reverse-phase high pressure liquid chromatography indicated that peptides coeluting with NT and its N-terminal partial sequences NT(1-8) and NT(1-11) were present in plasma. Comparison of plasmas collected before and 1 h after a defined meal, in five experiments, demonstrated no change in C-terminal immunoreactivity and an 8-to 10-fold rise in N-terminal immunoreactivity. Chromatographic analysis of pooled pre-and postmeal plasma in four experiments showed that essentially all of this elevation in neurotensinlike immunoreactivity measured with an N-terminal directed antiserum was due to increases in NT(1-8) and NT(1-11), while NT itself, measured using a C-terminal directed antiserum, did not increase appreciably in peripheral plasma 1 h after the meal. Generation of tritiated substances with the same elution times as NT(1-8) and NT(1-11) did occur after incubation of [3H]NT

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Section: Discussionmentioning

confidence: 64%

Elevation of Plasma Neurotensinlike Immunoreactivity after a Meal

Hammer¹,

Carraway²,

Leeman³

1982

J. Clin. Invest.

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“…The nanospray conditions on the Nanomate were as follows: 15 μl of sample injection, 16min of delivery time, 0.4 psi of gas pressure, and 1.5 kV of negative applied voltage. The Orbitrap Fusion MS analysis conditions were as follows: mass resolution of 450,000 with lock mass using internal calibrant, scan range of m/z 150 – 1600, % S-Lens RF Level of 60, 1.0e 5 for AGC Target, 100 msec maximum injection time, and 10 averaged microscans. The ion transfer tube temperature was 275°C, and the experimental mass accuracy was ± ~1 ppm.…”

Section: Methodsmentioning

confidence: 99%

“…Neurotensin (NT), a 13-amino acid peptide predominantly localized in specialized enteroendocrine (EE) cells of the small bowel 4 and released by fat ingestion 5 , facilitates fatty acid (FA) translocation in rat intestine 6 , and stimulates growth of various cancers 7 ; the effects of NT are mediated through three known NT receptors (NTR1, 2 and 3) 8 . Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality 9 ; however, a role for NT as a causative factor in these diseases is unknown.…”

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confidence: 99%

An obligatory role for neurotensin in high-fat-diet-induced obesity

Song

Zaytseva

et al. 2016

Nature

219

237

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Obesity and its associated comorbidities (e.g., diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually1 and are among the most prevalent and challenging conditions confronting the medical profession2,3. Neurotensin (NT), a 13-amino acid peptide predominantly localized in specialized enteroendocrine (EE) cells of the small bowel4 and released by fat ingestion5, facilitates fatty acid (FA) translocation in rat intestine6, and stimulates growth of various cancers7; the effects of NT are mediated through three known NT receptors (NTR1, 2 and 3)8. Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality9; however, a role for NT as a causative factor in these diseases is unknown. Here, we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates FA absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3/sortilin. Consistent with the findings in mice, expression of NT in Drosophila midgut EE cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment.

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“…It is well established (15,17) that lipids stimulate intestinal NT secretion. In this study, we show that postprandial blood levels of NT in rats are decreased by feeding chow containing TC and cholic acid, whereas they are increased by feeding chow containing the BA chelator cholestyramine.…”

Section: Effects Of Ba On Nt Mrna Expression and Secretionmentioning

confidence: 99%

Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats

Gui¹,

Dobner

Carraway³

2001

American Journal of Physiology-Gastrointestinal and Liver Physi

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away. Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats. Am J Physiol Gastrointest Liver Physiol 281: G1413-G1422, 2001.-Initial studies on the digestive hormone neurotensin (NT) showing that intestinal NT mRNA expression and blood levels were altered in rats fed chow containing bile acid (BA) and the BA chelator cholestyramine led us to investigate the role of NT in the enterohepatic circulation of BA. In fasted, anesthetized rats with common bile ducts cannulated for bile collection, intravenous NT infusion (10 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) enhanced BA output relative to control over 3 h in animals administered donor bile into the duodenum (30 l/min). This suggested that the effect of NT was on the return of BA from the intestine to the liver, which is rate determining in the normal process. In rats prepared as described above and administered

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Elevation of plasma neurotensin during lipid perfusion of rat small intestine

Cited by 80 publications

References 12 publications

Elevation of Plasma Neurotensinlike Immunoreactivity after a Meal

Elevation of Plasma Neurotensinlike Immunoreactivity after a Meal

An obligatory role for neurotensin in high-fat-diet-induced obesity

Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats

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