Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition

Roger Maldonado-Ruiz, Marcela Cárdenas-Tueme, Larisa Montalvo-Martínez, Román Vidaltamayo, Lourdes Garza-Ocañas, Diana Reséndez-Pérez, Alberto Camacho

Research output: Contribution to journalArticle

Abstract

Maternal overnutrition during pregnancy leads to metabolic alterations, including obesity, hyperphagia, and inflammation in the offspring. Nutritional priming of central inflammation and its role in ghrelin sensitivity during fed and fasted states have not been analyzed. The current study aims to identify the effect of maternal programming on microglia activation and ghrelin-induced activation of hypothalamic neurons leading to food intake response. We employed a nutritional programming model exposing female Wistar rats to a cafeteria diet (CAF) from pre-pregnancy to weaning. Food intake in male offspring was determined daily after fasting and subcutaneous injection of ghrelin. Hypothalamic ghrelin sensitivity and microglia activation was evaluated using immunodetection for Iba-1 and c-Fos markers, and Western blot for TBK1 signaling. Release of TNF-alpha, IL-6, and IL-1β after stimulation with palmitic, oleic, linoleic acid, or C6 ceramide in primary microglia culture were quantified using ELISA. We found that programmed offspring by CAF diet exhibits overfeeding after fasting and peripheral ghrelin administration, which correlates with an increase in the hypothalamic Iba-1 microglia marker and c-Fos cell activation. Additionally, in contrast to oleic, linoleic, or C6 ceramide stimulation in primary microglia culture, stimulation with palmitic acid for 24 h promotes TNF-alpha, IL-6, and IL-1β release and TBK1 activation. Notably, intracerebroventricular (i.c.v.) palmitic acid or LPS inoculation for five days promotes daily increase in food intake and food consumption after ghrelin administration. Finally, we found that i.c.v. palmitic acid substantially activates hypothalamic Iba-1 microglia marker and c-Fos. Together, our results suggest that maternal nutritional programing primes ghrelin sensitivity and microglia activation, which potentially might mirror hypothalamic administration of the saturated palmitic acid.
Original languageEnglish
Article number1241
JournalNutrients
Volume11
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

Fingerprint

Overnutrition
ghrelin
Ghrelin
neuroglia
Microglia
Mothers
Palmitic Acid
palmitic acid
rats
food intake
ceramides
Eating
interleukin-1
Diet
Interleukin-1
interleukin-6
tumor necrosis factor-alpha
fasting
Interleukin-6
Fasting

All Science Journal Classification (ASJC) codes

  • Food Science
  • Nutrition and Dietetics

Cite this

Maldonado-Ruiz, R., Cárdenas-Tueme, M., Montalvo-Martínez, L., Vidaltamayo, R., Garza-Ocañas, L., Reséndez-Pérez, D., & Camacho, A. (2019). Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition. Nutrients, 11(6), [1241]. https://doi.org/10.3390/nu11061241
Maldonado-Ruiz, Roger ; Cárdenas-Tueme, Marcela ; Montalvo-Martínez, Larisa ; Vidaltamayo, Román ; Garza-Ocañas, Lourdes ; Reséndez-Pérez, Diana ; Camacho, Alberto. / Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition. In: Nutrients. 2019 ; Vol. 11, No. 6.
@article{36d5596e04264923a9b7185a16a9b926,
title = "Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition",
abstract = "Maternal overnutrition during pregnancy leads to metabolic alterations, including obesity, hyperphagia, and inflammation in the offspring. Nutritional priming of central inflammation and its role in ghrelin sensitivity during fed and fasted states have not been analyzed. The current study aims to identify the effect of maternal programming on microglia activation and ghrelin-induced activation of hypothalamic neurons leading to food intake response. We employed a nutritional programming model exposing female Wistar rats to a cafeteria diet (CAF) from pre-pregnancy to weaning. Food intake in male offspring was determined daily after fasting and subcutaneous injection of ghrelin. Hypothalamic ghrelin sensitivity and microglia activation was evaluated using immunodetection for Iba-1 and c-Fos markers, and Western blot for TBK1 signaling. Release of TNF-alpha, IL-6, and IL-1β after stimulation with palmitic, oleic, linoleic acid, or C6 ceramide in primary microglia culture were quantified using ELISA. We found that programmed offspring by CAF diet exhibits overfeeding after fasting and peripheral ghrelin administration, which correlates with an increase in the hypothalamic Iba-1 microglia marker and c-Fos cell activation. Additionally, in contrast to oleic, linoleic, or C6 ceramide stimulation in primary microglia culture, stimulation with palmitic acid for 24 h promotes TNF-alpha, IL-6, and IL-1β release and TBK1 activation. Notably, intracerebroventricular (i.c.v.) palmitic acid or LPS inoculation for five days promotes daily increase in food intake and food consumption after ghrelin administration. Finally, we found that i.c.v. palmitic acid substantially activates hypothalamic Iba-1 microglia marker and c-Fos. Together, our results suggest that maternal nutritional programing primes ghrelin sensitivity and microglia activation, which potentially might mirror hypothalamic administration of the saturated palmitic acid.",
author = "Roger Maldonado-Ruiz and Marcela C{\'a}rdenas-Tueme and Larisa Montalvo-Mart{\'i}nez and Rom{\'a}n Vidaltamayo and Lourdes Garza-Oca{\~n}as and Diana Res{\'e}ndez-P{\'e}rez and Alberto Camacho",
year = "2019",
month = "6",
day = "1",
doi = "https://doi.org/10.3390/nu11061241",
language = "English",
volume = "11",
journal = "Nutrients",
issn = "2072-6643",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",

}

Maldonado-Ruiz, R, Cárdenas-Tueme, M, Montalvo-Martínez, L, Vidaltamayo, R, Garza-Ocañas, L, Reséndez-Pérez, D & Camacho, A 2019, 'Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition', Nutrients, vol. 11, no. 6, 1241. https://doi.org/10.3390/nu11061241

Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition. / Maldonado-Ruiz, Roger; Cárdenas-Tueme, Marcela; Montalvo-Martínez, Larisa; Vidaltamayo, Román; Garza-Ocañas, Lourdes; Reséndez-Pérez, Diana; Camacho, Alberto.

In: Nutrients, Vol. 11, No. 6, 1241, 01.06.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition

AU - Maldonado-Ruiz, Roger

AU - Cárdenas-Tueme, Marcela

AU - Montalvo-Martínez, Larisa

AU - Vidaltamayo, Román

AU - Garza-Ocañas, Lourdes

AU - Reséndez-Pérez, Diana

AU - Camacho, Alberto

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Maternal overnutrition during pregnancy leads to metabolic alterations, including obesity, hyperphagia, and inflammation in the offspring. Nutritional priming of central inflammation and its role in ghrelin sensitivity during fed and fasted states have not been analyzed. The current study aims to identify the effect of maternal programming on microglia activation and ghrelin-induced activation of hypothalamic neurons leading to food intake response. We employed a nutritional programming model exposing female Wistar rats to a cafeteria diet (CAF) from pre-pregnancy to weaning. Food intake in male offspring was determined daily after fasting and subcutaneous injection of ghrelin. Hypothalamic ghrelin sensitivity and microglia activation was evaluated using immunodetection for Iba-1 and c-Fos markers, and Western blot for TBK1 signaling. Release of TNF-alpha, IL-6, and IL-1β after stimulation with palmitic, oleic, linoleic acid, or C6 ceramide in primary microglia culture were quantified using ELISA. We found that programmed offspring by CAF diet exhibits overfeeding after fasting and peripheral ghrelin administration, which correlates with an increase in the hypothalamic Iba-1 microglia marker and c-Fos cell activation. Additionally, in contrast to oleic, linoleic, or C6 ceramide stimulation in primary microglia culture, stimulation with palmitic acid for 24 h promotes TNF-alpha, IL-6, and IL-1β release and TBK1 activation. Notably, intracerebroventricular (i.c.v.) palmitic acid or LPS inoculation for five days promotes daily increase in food intake and food consumption after ghrelin administration. Finally, we found that i.c.v. palmitic acid substantially activates hypothalamic Iba-1 microglia marker and c-Fos. Together, our results suggest that maternal nutritional programing primes ghrelin sensitivity and microglia activation, which potentially might mirror hypothalamic administration of the saturated palmitic acid.

AB - Maternal overnutrition during pregnancy leads to metabolic alterations, including obesity, hyperphagia, and inflammation in the offspring. Nutritional priming of central inflammation and its role in ghrelin sensitivity during fed and fasted states have not been analyzed. The current study aims to identify the effect of maternal programming on microglia activation and ghrelin-induced activation of hypothalamic neurons leading to food intake response. We employed a nutritional programming model exposing female Wistar rats to a cafeteria diet (CAF) from pre-pregnancy to weaning. Food intake in male offspring was determined daily after fasting and subcutaneous injection of ghrelin. Hypothalamic ghrelin sensitivity and microglia activation was evaluated using immunodetection for Iba-1 and c-Fos markers, and Western blot for TBK1 signaling. Release of TNF-alpha, IL-6, and IL-1β after stimulation with palmitic, oleic, linoleic acid, or C6 ceramide in primary microglia culture were quantified using ELISA. We found that programmed offspring by CAF diet exhibits overfeeding after fasting and peripheral ghrelin administration, which correlates with an increase in the hypothalamic Iba-1 microglia marker and c-Fos cell activation. Additionally, in contrast to oleic, linoleic, or C6 ceramide stimulation in primary microglia culture, stimulation with palmitic acid for 24 h promotes TNF-alpha, IL-6, and IL-1β release and TBK1 activation. Notably, intracerebroventricular (i.c.v.) palmitic acid or LPS inoculation for five days promotes daily increase in food intake and food consumption after ghrelin administration. Finally, we found that i.c.v. palmitic acid substantially activates hypothalamic Iba-1 microglia marker and c-Fos. Together, our results suggest that maternal nutritional programing primes ghrelin sensitivity and microglia activation, which potentially might mirror hypothalamic administration of the saturated palmitic acid.

UR - http://www.scopus.com/inward/record.url?scp=85067174519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067174519&partnerID=8YFLogxK

U2 - https://doi.org/10.3390/nu11061241

DO - https://doi.org/10.3390/nu11061241

M3 - Article

VL - 11

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 6

M1 - 1241

ER -