Neurotensin
A 13-amino-acid peptide that acts as a neurotransmitter in the brain and a hormone in the gut
Neurotensin is a tridecapeptide found in the brain and the gastrointestinal tract, first isolated in 1973 from bovine hypothalami as a peptide that lowers blood pressure. It modulates dopamine and other transmitter systems and, in the gut, motility and fat absorption. It is a research molecule, not a medicine.
What is it?
In the brain neurotensin behaves as a neurotransmitter and modulates dopaminergic, serotonergic, GABAergic, glutamatergic and cholinergic systems, which is why it has been studied in schizophrenia, addiction and pain. In the gut it acts as a hormone: infused into healthy adults, it set off bowel movements within hours.
Human data remain sparse and indirect. Infused into volunteers, it changed how the rectum and colon stretch; after diet-induced weight loss its levels fell, and larger meal responses marked those who kept the weight off. Its stable precursor fragment tracked insulin sensitivity after bariatric surgery, a radiolabelled analogue was taken up by a receptor-rich pancreatic tumour, and people with Parkinson's disease had lower levels of naturally occurring neurotensin-binding antibodies.
Its stable precursor fragment, pro-neurotensin, has become the main human measurement. In a Swedish cohort followed for about 20 years, the top quartile carried a 29% higher risk of death and 41% higher risk of cardiovascular death; higher levels also went with fatty liver. It did not predict hypertension or new kidney disease. Paradoxically, it rises after both surgical and lifestyle weight loss.
Brain and cancer work runs alongside. Genetic studies link higher pro-neurotensin to differences in reward-related brain regions, and a gene variant raised plasma neurotensin in schizophrenia. In mice, loss of neurotensin in a reward pathway blunted pleasure-driven eating on a high-fat diet. In oncology, a first-in-human neurotensin PET tracer missed untreated prostate cancer that PSMA found, and high receptor expression marked a poor-prognosis colorectal cancer subtype.
Mechanism of Action
Neurotensin is a neuropeptide in the brain and a hormone in the gut; its stable precursor fragment, pro-neurotensin, is what blood studies measure.
Brain signalling
It modulates dopamine and other transmitter systems, which links it to reward, schizophrenia and pain.
Gut and fat
Infused, it triggered bowel movements; in mice it promoted fat uptake into the liver.
Tumour receptors
Some cancers carry its NTSR1 receptor, which is targeted for imaging and radioligand therapy.
Published Research
Studies read from their PubMed abstracts, with one review; the 1973 discovery paper has no abstract and is listed in References only.
It moves the bowel
In a double-blind study, five healthy adults defaecated within 2.5 hours of a 30-minute neurotensin infusion and none after control infusions; blood levels during infusion were about three times normal post-meal levels.
After bariatric surgery
In 20 people with severe obesity randomised to two types of metabolic surgery, proneurotensin rose and correlated with insulin sensitivity only after surgery-induced weight loss, more so after biliopancreatic diversion.
A tumour-seeking analogue
In four patients with pancreatic adenocarcinoma, the technetium-labelled analogue NT-XI was well tolerated and was taken up specifically by the one tumour rich in neurotensin receptors.
Antibodies in Parkinson's disease
Neurotensin-binding IgG occurs naturally in people, and patients with Parkinson's disease had lower plasma levels, lower still with more severe disease.
Rectum and colon in volunteers
In eight healthy volunteers, a neurotensin infusion (5 pmol/kg per minute) made the rectum and colon more compliant and increased urge and pain during rectal distension, without changing sensation in the colon.
Weight-loss maintenance
In 42 adults with obesity, an 8-week low-calorie diet that took off 13% of body weight cut fasting neurotensin by 40%; those who kept losing weight over the next year had larger meal-induced neurotensin peaks than those who regained.
Pro-neurotensin and death over 20 years
In a middle-aged Swedish cohort followed about 20 years, the top quartile of pro-neurotensin (149 pmol/L or more) carried a 29% higher risk of death and 41% higher risk of cardiovascular death.
Fatty liver
Higher pro-neurotensin went with more fat, worse lipids and insulin resistance, and a 3.4-fold higher odds of NAFLD in the top against the bottom tertile.
Kidney outcomes (REGARDS)
In 3,914 adults, higher pro-neurotensin was associated with slightly greater odds of eGFR decline but not with new CKD, albuminuria or kidney failure.
No link with hypertension
In a prospective study with 614 new hypertension cases over 9.4 years, baseline pro-neurotensin was not associated with developing hypertension.
Diet and bariatric surgery
Very-low-energy diets and the early weeks after gastric bypass lowered pro-neurotensin; a meal response absent before surgery appeared afterwards, and fasting levels were higher a year later.
Lifestyle weight loss
In a randomised lifestyle trial, the intervention group lost 2.5 kg and pro-neurotensin rose by 28.2 pmol/L against 3.5 in controls, the same paradox seen after surgery.
Genetics and brain structure
Genome-wide analysis found three loci for serum pro-neurotensin, and Mendelian randomisation linked higher levels to differences in the pallidum and brainstem and weaker reward-network coherence.
A variant in schizophrenia
In schizophrenia, carriers of a deletion variant in the neurotensin gene had higher plasma neurotensin, which correlated with symptom scores and BMI; the link was absent in controls.
First-in-human prostate cancer PET
A fluorine-18 neurotensin tracer found no lesions in untreated prostate cancer where PSMA PET found 36 of 38, but its sensitivity rose after androgen-deprivation therapy as PSMA's fell.
Receptor expression in colorectal cancer
High expression of the neurotensin receptor NTSR1 defined an immune-cold colorectal cancer subtype with worse progression-free and overall survival.
Roles in the brain
A review describing neurotensin as a neurotransmitter in the brain and a hormone in the gut that modulates several transmitter systems, and its links to schizophrenia and other CNS disorders.
A brake on heat production
Single-cell profiling of human and mouse tissue found lymphatic endothelial cells make neurotensin, which restrained thermogenesis through NTSR2 in mice; blocking NTSR2 raised energy expenditure in obese mice.
Reward
A review of neurotensin's roles in temperature regulation, feeding, pain, ethanol sensitivity and reward, centred on the ventral tegmental area and widening to other brain regions.
Energy balance
A review tracing the neurotensin system from the brain through the enteric nervous system to the periphery as a regulator of energy balance and a possible therapeutic target.
Hedonic eating in obese mice
In mice on a high-fat diet, reduced neurotensin in a reward pathway blunted pleasure-driven eating, and restoring neurotensin normalised aspects of diet-induced obesity.
Fatty liver mechanism
Neurotensin promoted fat uptake into liver cells in mice, its absence protected the liver, and its signalling was raised in human MASLD and MASH samples.
Dosing Data
Neurotensin is not a treatment. Research infusions in volunteers used 5 to 13.5 pmol/kg/min.
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Side Effects & Contraindications
Reported Side Effects
From the human studies.
Contraindications & Cautions
Not a medicine.
Legal Status
Not a medicine.
Frequently Asked Questions
?Is neurotensin used as a drug?
No. It is studied as a brain and gut signal; one radiolabelled analogue was tested for tumour imaging in a small study.
?What does it do in the gut?
Infused into healthy adults, it stimulated colonic motility and bowel movements within hours.
?Why is it linked to schizophrenia?
It modulates dopamine and other transmitter systems in the brain, which is why reviews connect it with several CNS disorders.
?Does neurotensin affect body weight?
In mice it restrained heat production through the NTSR2 receptor, and in people its precursor tracked insulin sensitivity after bariatric surgery; no treatment exists.
?What is pro-neurotensin?
A stable fragment of neurotensin's precursor that is measured in blood. High levels predicted death and cardiovascular death over 20 years in a Swedish cohort and went with fatty liver, but not with new hypertension.
?Is neurotensin used in cancer imaging?
Its receptor is a target. A first-in-human neurotensin PET tracer missed untreated prostate cancer that PSMA PET detected, though it picked up more after hormone therapy.
References
- [clinical-trial] Calam J, et al. "Neurotensin stimulates defaecation." Lancet, 1983;1(8327):737-8. PMID: 6132085.
- [clinical-trial] von Loeffelholz C, et al. "The anorexigenic peptide neurotensin relates to insulin sensitivity in obese patients after BPD or RYGB metabolic surgery." Int J Obes (Lond), 2018;42(12):2057-2061. PMID: 29795470.
- [pubmed] Buchegger F, et al. "Radiolabeled neurotensin analog, 99mTc-NT-XI, evaluated in ductal pancreatic adenocarcinoma patients." J Nucl Med, 2003;44(10):1649-54. PMID: 14530481.
- [pubmed] Muruzheva ZM, et al. "Neurotensin-Binding Immunoglobulin G in Patients with Parkinson's Disease." Neuroimmunomodulation, 2023;30(1):15-27. PMID: 36516809.
- [review] Boules M, et al. "Diverse roles of neurotensin agonists in the central nervous system." Front Endocrinol (Lausanne), 2013;4:36. PMID: 23526754.
- [pubmed] Li J, et al. "Neurotensin is an anti-thermogenic peptide produced by lymphatic endothelial cells." Cell Metab, 2021;33(7):1449-1465.e6. PMID: 34038712.
- [review] Torruella-Suárez ML, et al. "Neurotensin in reward processes." Neuropharmacology, 2020;167:108005. PMID: 32057800.
- [review] Gereau GB, et al. "Neurotensin and energy balance." J Neurochem, 2023;166(2):189-200. PMID: 37309600.
- [pubmed] Carraway R, et al. "The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami." J Biol Chem, 1973;248(19):6854-61. PMID: 4745447.
- [pubmed] van der Veek PP, et al. "Effect of neurotensin on colorectal motor and sensory function in humans." Dis Colon Rectum, 2004;47(2):210-8. PMID: 15043292.
- [pubmed] Brethvad AO, et al. "Increased meal-induced neurotensin response predicts successful maintenance of weight loss - Data from a randomized controlled trial." Metabolism, 2023;143:155534. PMID: 36933790.
- [pubmed] Fawad A, et al. "Plasma Proneurotensin and Prediction of Cause-Specific Mortality in a Middle-aged Cohort During Long-term Follow-up." J Clin Endocrinol Metab, 2022;107(3):e1204-e1211. PMID: 34665860.
- [pubmed] De Vito F, et al. "Higher circulating levels of proneurotensin are associated with increased risk of incident NAFLD." J Intern Med, 2023;294(3):336-346. PMID: 37157165.
- [pubmed] Bullen AL, et al. "Proneurotensin/Neuromedin N and Risk of Incident CKD and Other Kidney Outcomes in Community-Living Individuals: The REGARDS Study." Kidney Med, 2024;6(6):100831. PMID: 38774125.
- [pubmed] Nicoli CD, et al. "Pro-neurotensin/Neuromedin N and Hypertension Risk: A Prospective Study." Am J Hypertens, 2022;35(3):281-288. PMID: 34655288.
- [pubmed] Miskelly MG, et al. "The Effects of Calorie Restriction and Bariatric Surgery on Circulating Proneurotensin Levels." J Clin Endocrinol Metab, 2025;110(2):e497-e505. PMID: 38477483.
- [pubmed] Bennet L, et al. "The effect of a randomised controlled lifestyle intervention on weight loss and plasma proneurotensin." BMC Endocr Disord, 2022;22(1):264. PMID: 36316682.
- [pubmed] Breitfeld J, et al. "Genetic dissection of serum pro-neurotensin suggests potential causal impact on brain structure." EBioMedicine, 2026;124:106105. PMID: 41520650.
- [pubmed] Pirim D, et al. "The rs139226362 (delGATT) variant in the NTS gene alters plasma neurotensin levels in schizophrenia." Biomark Med, 2025;19(22):1137-1146. PMID: 41251017.
- [pubmed] He J, et al. "First-in-human evaluation of [(18)F]-AlF-NOTA-neurotensin for NTSR1-targeted imaging of prostate cancer: a head-to-head comparison with [(68)Ga]Ga-PSMA-617." Ann Med, 2026;58(1):2678019. PMID: 42304982.
- [pubmed] Wu H, et al. "Expression of the High-affinity Neurotensin Receptor Defines an Immune‑cold, Poor‑prognosis Colorectal Cancer Subtype." Ann Surg, 2026;284(3):458-471. PMID: 42322125.
- [pubmed] Gazit Shimoni N, et al. "Changes in neurotensin signalling drive hedonic devaluation in obesity." Nature, 2025;641(8065):1238-1247. PMID: 40140571.
- [pubmed] Banerjee M, et al. "Neurotensin promotes hepatic steatosis by regulating lipid uptake and mitochondrial adaptation in hepatocytes." Cell Death Dis, 2025;16(1):347. PMID: 40287434.
Sources & Citations
Studies were read from their PubMed abstracts. Read October 7, 2026.
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