Increased meal-induced neurotensin response predicts successful maintenance of weight loss: Data from a randomized controlled trial

Research output: Contribution to journalJournal articlepeer-review

Standard

Increased meal-induced neurotensin response predicts successful maintenance of weight loss : Data from a randomized controlled trial. / Brethvad, Annemette Overgaard; Zakariassen, Hannah Louise; Holt, Joachim; Lundgren, Julie Rehné; Jakobsen, Alexander; Hartmann, Bolette; Lehmann, Eva Winning; Kissow, Hannelouise; Holst, Jens Juul; Madsbad, Sten; Torekov, Signe Sørensen; Holst, Birgitte.

In: Metabolism: Clinical and Experimental, Vol. 143, 155534, 2023.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Brethvad, AO, Zakariassen, HL, Holt, J, Lundgren, JR, Jakobsen, A, Hartmann, B, Lehmann, EW, Kissow, H, Holst, JJ, Madsbad, S, Torekov, SS & Holst, B 2023, 'Increased meal-induced neurotensin response predicts successful maintenance of weight loss: Data from a randomized controlled trial', Metabolism: Clinical and Experimental, vol. 143, 155534. https://doi.org/10.1016/j.metabol.2023.155534

APA

Brethvad, A. O., Zakariassen, H. L., Holt, J., Lundgren, J. R., Jakobsen, A., Hartmann, B., Lehmann, E. W., Kissow, H., Holst, J. J., Madsbad, S., Torekov, S. S., & Holst, B. (2023). Increased meal-induced neurotensin response predicts successful maintenance of weight loss: Data from a randomized controlled trial. Metabolism: Clinical and Experimental, 143, [155534]. https://doi.org/10.1016/j.metabol.2023.155534

Vancouver

Brethvad AO, Zakariassen HL, Holt J, Lundgren JR, Jakobsen A, Hartmann B et al. Increased meal-induced neurotensin response predicts successful maintenance of weight loss: Data from a randomized controlled trial. Metabolism: Clinical and Experimental. 2023;143. 155534. https://doi.org/10.1016/j.metabol.2023.155534

Author

Brethvad, Annemette Overgaard ; Zakariassen, Hannah Louise ; Holt, Joachim ; Lundgren, Julie Rehné ; Jakobsen, Alexander ; Hartmann, Bolette ; Lehmann, Eva Winning ; Kissow, Hannelouise ; Holst, Jens Juul ; Madsbad, Sten ; Torekov, Signe Sørensen ; Holst, Birgitte. / Increased meal-induced neurotensin response predicts successful maintenance of weight loss : Data from a randomized controlled trial. In: Metabolism: Clinical and Experimental. 2023 ; Vol. 143.

Bibtex

@article{f1f12c0e8c77473b81b680c79189779d,
title = "Increased meal-induced neurotensin response predicts successful maintenance of weight loss: Data from a randomized controlled trial",
abstract = "BACKGROUND: The gut derived anorexigenic hormone neurotensin (NT) is upregulated after bariatric surgery which may contribute to the sustained weight loss. In contrast, diet-induced weight loss is most often followed by weight regain. We therefore investigated whether diet-induced weight loss impacts levels of circulating NT in mice and humans and whether NT levels predicts body weight change after weight loss in humans.METHODS: In vivo mice study: Obese mice were fed ad-libitum or a restricted diet (40-60 % of average food intake) for 9 days to obtain similar weight loss as observed in the human study. At termination, intestinal segments, the hypothalamus and plasma were collected for histological, real time PCR, and radioimmunoassay (RIA) analysis.CLINICAL TRIAL: Plasma samples from 42 participants with obesity, completing an 8-week low-calorie diet in a randomized controlled trial, were analyzed. Plasma NT was measured by RIA at fasting and during a meal test before and after diet-induced weight loss and after one year of intended weight maintenance.RESULTS: In obese mice, food restriction-induced body weight loss of 14 % was associated with a 64 % reduction in fasting plasma NT (p < 0.0001). In the mouse duodenum (p = 0.07) and jejunum (p < 0.05), NT tissue concentration was decreased without tissue atrophy indicative of a physiological downregulation. In the mouse hypothalamus a downregulation of Pomc (p < 0.01) along with upregulation of Npy (p < 0.001) and Agrp (p < 0.0001) expression was found after restricted feeding in support of increased hunger after diet-induced weight loss. Therefore, we investigated the NT response in humans undergoing weight loss maintenance. In humans, similar to the mice, the low-calorie diet induced weight loss of 13 % body weight was associated with 40 % reduction in fasting plasma NT levels (p < 0.001). Meal-induced NT peak responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight (p < 0.05).CONCLUSION: Diet-induced weight loss decreased fasting plasma NT levels in both humans and mice with obesity, and regulated hunger-associated hypothalamic gene expression in mice. Meal-induced NT responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight. This indicates that increased peak secretion of NT after weight loss may contribute to successful maintenance of weight loss.CLINICAL TRIAL REGISTRATION NUMBER: NCT02094183.",
author = "Brethvad, {Annemette Overgaard} and Zakariassen, {Hannah Louise} and Joachim Holt and Lundgren, {Julie Rehn{\'e}} and Alexander Jakobsen and Bolette Hartmann and Lehmann, {Eva Winning} and Hannelouise Kissow and Holst, {Jens Juul} and Sten Madsbad and Torekov, {Signe S{\o}rensen} and Birgitte Holst",
note = "Copyright {\textcopyright} 2023. Published by Elsevier Inc.",
year = "2023",
doi = "10.1016/j.metabol.2023.155534",
language = "English",
volume = "143",
journal = "Metabolism",
issn = "0026-0495",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Increased meal-induced neurotensin response predicts successful maintenance of weight loss

T2 - Data from a randomized controlled trial

AU - Brethvad, Annemette Overgaard

AU - Zakariassen, Hannah Louise

AU - Holt, Joachim

AU - Lundgren, Julie Rehné

AU - Jakobsen, Alexander

AU - Hartmann, Bolette

AU - Lehmann, Eva Winning

AU - Kissow, Hannelouise

AU - Holst, Jens Juul

AU - Madsbad, Sten

AU - Torekov, Signe Sørensen

AU - Holst, Birgitte

N1 - Copyright © 2023. Published by Elsevier Inc.

PY - 2023

Y1 - 2023

N2 - BACKGROUND: The gut derived anorexigenic hormone neurotensin (NT) is upregulated after bariatric surgery which may contribute to the sustained weight loss. In contrast, diet-induced weight loss is most often followed by weight regain. We therefore investigated whether diet-induced weight loss impacts levels of circulating NT in mice and humans and whether NT levels predicts body weight change after weight loss in humans.METHODS: In vivo mice study: Obese mice were fed ad-libitum or a restricted diet (40-60 % of average food intake) for 9 days to obtain similar weight loss as observed in the human study. At termination, intestinal segments, the hypothalamus and plasma were collected for histological, real time PCR, and radioimmunoassay (RIA) analysis.CLINICAL TRIAL: Plasma samples from 42 participants with obesity, completing an 8-week low-calorie diet in a randomized controlled trial, were analyzed. Plasma NT was measured by RIA at fasting and during a meal test before and after diet-induced weight loss and after one year of intended weight maintenance.RESULTS: In obese mice, food restriction-induced body weight loss of 14 % was associated with a 64 % reduction in fasting plasma NT (p < 0.0001). In the mouse duodenum (p = 0.07) and jejunum (p < 0.05), NT tissue concentration was decreased without tissue atrophy indicative of a physiological downregulation. In the mouse hypothalamus a downregulation of Pomc (p < 0.01) along with upregulation of Npy (p < 0.001) and Agrp (p < 0.0001) expression was found after restricted feeding in support of increased hunger after diet-induced weight loss. Therefore, we investigated the NT response in humans undergoing weight loss maintenance. In humans, similar to the mice, the low-calorie diet induced weight loss of 13 % body weight was associated with 40 % reduction in fasting plasma NT levels (p < 0.001). Meal-induced NT peak responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight (p < 0.05).CONCLUSION: Diet-induced weight loss decreased fasting plasma NT levels in both humans and mice with obesity, and regulated hunger-associated hypothalamic gene expression in mice. Meal-induced NT responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight. This indicates that increased peak secretion of NT after weight loss may contribute to successful maintenance of weight loss.CLINICAL TRIAL REGISTRATION NUMBER: NCT02094183.

AB - BACKGROUND: The gut derived anorexigenic hormone neurotensin (NT) is upregulated after bariatric surgery which may contribute to the sustained weight loss. In contrast, diet-induced weight loss is most often followed by weight regain. We therefore investigated whether diet-induced weight loss impacts levels of circulating NT in mice and humans and whether NT levels predicts body weight change after weight loss in humans.METHODS: In vivo mice study: Obese mice were fed ad-libitum or a restricted diet (40-60 % of average food intake) for 9 days to obtain similar weight loss as observed in the human study. At termination, intestinal segments, the hypothalamus and plasma were collected for histological, real time PCR, and radioimmunoassay (RIA) analysis.CLINICAL TRIAL: Plasma samples from 42 participants with obesity, completing an 8-week low-calorie diet in a randomized controlled trial, were analyzed. Plasma NT was measured by RIA at fasting and during a meal test before and after diet-induced weight loss and after one year of intended weight maintenance.RESULTS: In obese mice, food restriction-induced body weight loss of 14 % was associated with a 64 % reduction in fasting plasma NT (p < 0.0001). In the mouse duodenum (p = 0.07) and jejunum (p < 0.05), NT tissue concentration was decreased without tissue atrophy indicative of a physiological downregulation. In the mouse hypothalamus a downregulation of Pomc (p < 0.01) along with upregulation of Npy (p < 0.001) and Agrp (p < 0.0001) expression was found after restricted feeding in support of increased hunger after diet-induced weight loss. Therefore, we investigated the NT response in humans undergoing weight loss maintenance. In humans, similar to the mice, the low-calorie diet induced weight loss of 13 % body weight was associated with 40 % reduction in fasting plasma NT levels (p < 0.001). Meal-induced NT peak responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight (p < 0.05).CONCLUSION: Diet-induced weight loss decreased fasting plasma NT levels in both humans and mice with obesity, and regulated hunger-associated hypothalamic gene expression in mice. Meal-induced NT responses were greater in humans who lost additional weight during the 1 year maintenance phase compared to participants who regained weight. This indicates that increased peak secretion of NT after weight loss may contribute to successful maintenance of weight loss.CLINICAL TRIAL REGISTRATION NUMBER: NCT02094183.

U2 - 10.1016/j.metabol.2023.155534

DO - 10.1016/j.metabol.2023.155534

M3 - Journal article

C2 - 36933790

VL - 143

JO - Metabolism

JF - Metabolism

SN - 0026-0495

M1 - 155534

ER -

ID: 339629789