Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny

Jill S. Carmody, Phyllis Wan, Domenico Accili, Lori M. Zeltser, Rudolph L. Leibel

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Maternal obesity can influence susceptibility to obesity and type 2 diabetes in progeny. We examined the relationship of maternal insulin resistance (IR), a metabolically important consequence of increased adiposity, to adverse consequences of obesity for fetal development. We used mice heterozygous for a null allele of the insulin receptor (Insr) to study the contributions of maternal IR to offspring phenotype without the potential confound of obesity per se, and how maternal consumption of high-fat diet (HFD) may, independently and interactively, affect progeny. In progeny fed a 60% HFD, body weight and adiposity were transiently (5-7 weeks) increased in wild-type (+/+) offspring of Insr+/- HFD-fed dams compared to offspring of wild-type HFD-fed dams. Offspring of HFD-fed wild-type dams had increased body weight, blood glucose, and plasma insulin concentrations compared to offspring of chow-fed wild-type dams. Quantification of proopiomelanocortin (POMC) and neuropeptide-Y (NPY) populations in the arcuate nucleus of the hypothalamus (ARH) of offspring of wild-type vs. Insr+/- dams was performed to determine whether maternal IR affects the formation of central feeding circuits. We found a 20% increase in the number of Pomc-expressing cells at postnatal day 9 in offspring of Insr+/- dams. In conclusion, maternal HFD consumption - distinct from overt obesity per se - was a major contributor to increased body weight, adiposity, IR, and liver triglyceride (TG) phenotypes in progeny. Maternal IR played a minor role in predisposing progeny to obesity and IR, though it acted synergistically with maternal HFD to exacerbate early obesity in progeny.

Original languageEnglish (US)
Pages (from-to)492-499
Number of pages8
JournalObesity
Volume19
Issue number3
DOIs
StatePublished - Mar 1 2011

Fingerprint

High Fat Diet
Insulin Resistance
Mothers
Diet
Obesity
Phenotype
Insulin Receptor
Adiposity
Body Weight
Pro-Opiomelanocortin
Arcuate Nucleus of Hypothalamus
Neuropeptide Y
Fetal Development
Type 2 Diabetes Mellitus
Blood Glucose
Triglycerides
Alleles
Insulin
Liver
Population

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny. / Carmody, Jill S.; Wan, Phyllis; Accili, Domenico; Zeltser, Lori M.; Leibel, Rudolph L.

In: Obesity, Vol. 19, No. 3, 01.03.2011, p. 492-499.

Research output: Contribution to journalArticle

Carmody, Jill S. ; Wan, Phyllis ; Accili, Domenico ; Zeltser, Lori M. ; Leibel, Rudolph L. / Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny. In: Obesity. 2011 ; Vol. 19, No. 3. pp. 492-499.
@article{44d90dca80544a429a78bd668df14c39,
title = "Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny",
abstract = "Maternal obesity can influence susceptibility to obesity and type 2 diabetes in progeny. We examined the relationship of maternal insulin resistance (IR), a metabolically important consequence of increased adiposity, to adverse consequences of obesity for fetal development. We used mice heterozygous for a null allele of the insulin receptor (Insr) to study the contributions of maternal IR to offspring phenotype without the potential confound of obesity per se, and how maternal consumption of high-fat diet (HFD) may, independently and interactively, affect progeny. In progeny fed a 60{\%} HFD, body weight and adiposity were transiently (5-7 weeks) increased in wild-type (+/+) offspring of Insr+/- HFD-fed dams compared to offspring of wild-type HFD-fed dams. Offspring of HFD-fed wild-type dams had increased body weight, blood glucose, and plasma insulin concentrations compared to offspring of chow-fed wild-type dams. Quantification of proopiomelanocortin (POMC) and neuropeptide-Y (NPY) populations in the arcuate nucleus of the hypothalamus (ARH) of offspring of wild-type vs. Insr+/- dams was performed to determine whether maternal IR affects the formation of central feeding circuits. We found a 20{\%} increase in the number of Pomc-expressing cells at postnatal day 9 in offspring of Insr+/- dams. In conclusion, maternal HFD consumption - distinct from overt obesity per se - was a major contributor to increased body weight, adiposity, IR, and liver triglyceride (TG) phenotypes in progeny. Maternal IR played a minor role in predisposing progeny to obesity and IR, though it acted synergistically with maternal HFD to exacerbate early obesity in progeny.",
author = "Carmody, {Jill S.} and Phyllis Wan and Domenico Accili and Zeltser, {Lori M.} and Leibel, {Rudolph L.}",
year = "2011",
month = "3",
day = "1",
doi = "10.1038/oby.2010.245",
language = "English (US)",
volume = "19",
pages = "492--499",
journal = "Obesity",
issn = "1930-7381",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny

AU - Carmody, Jill S.

AU - Wan, Phyllis

AU - Accili, Domenico

AU - Zeltser, Lori M.

AU - Leibel, Rudolph L.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Maternal obesity can influence susceptibility to obesity and type 2 diabetes in progeny. We examined the relationship of maternal insulin resistance (IR), a metabolically important consequence of increased adiposity, to adverse consequences of obesity for fetal development. We used mice heterozygous for a null allele of the insulin receptor (Insr) to study the contributions of maternal IR to offspring phenotype without the potential confound of obesity per se, and how maternal consumption of high-fat diet (HFD) may, independently and interactively, affect progeny. In progeny fed a 60% HFD, body weight and adiposity were transiently (5-7 weeks) increased in wild-type (+/+) offspring of Insr+/- HFD-fed dams compared to offspring of wild-type HFD-fed dams. Offspring of HFD-fed wild-type dams had increased body weight, blood glucose, and plasma insulin concentrations compared to offspring of chow-fed wild-type dams. Quantification of proopiomelanocortin (POMC) and neuropeptide-Y (NPY) populations in the arcuate nucleus of the hypothalamus (ARH) of offspring of wild-type vs. Insr+/- dams was performed to determine whether maternal IR affects the formation of central feeding circuits. We found a 20% increase in the number of Pomc-expressing cells at postnatal day 9 in offspring of Insr+/- dams. In conclusion, maternal HFD consumption - distinct from overt obesity per se - was a major contributor to increased body weight, adiposity, IR, and liver triglyceride (TG) phenotypes in progeny. Maternal IR played a minor role in predisposing progeny to obesity and IR, though it acted synergistically with maternal HFD to exacerbate early obesity in progeny.

AB - Maternal obesity can influence susceptibility to obesity and type 2 diabetes in progeny. We examined the relationship of maternal insulin resistance (IR), a metabolically important consequence of increased adiposity, to adverse consequences of obesity for fetal development. We used mice heterozygous for a null allele of the insulin receptor (Insr) to study the contributions of maternal IR to offspring phenotype without the potential confound of obesity per se, and how maternal consumption of high-fat diet (HFD) may, independently and interactively, affect progeny. In progeny fed a 60% HFD, body weight and adiposity were transiently (5-7 weeks) increased in wild-type (+/+) offspring of Insr+/- HFD-fed dams compared to offspring of wild-type HFD-fed dams. Offspring of HFD-fed wild-type dams had increased body weight, blood glucose, and plasma insulin concentrations compared to offspring of chow-fed wild-type dams. Quantification of proopiomelanocortin (POMC) and neuropeptide-Y (NPY) populations in the arcuate nucleus of the hypothalamus (ARH) of offspring of wild-type vs. Insr+/- dams was performed to determine whether maternal IR affects the formation of central feeding circuits. We found a 20% increase in the number of Pomc-expressing cells at postnatal day 9 in offspring of Insr+/- dams. In conclusion, maternal HFD consumption - distinct from overt obesity per se - was a major contributor to increased body weight, adiposity, IR, and liver triglyceride (TG) phenotypes in progeny. Maternal IR played a minor role in predisposing progeny to obesity and IR, though it acted synergistically with maternal HFD to exacerbate early obesity in progeny.

UR - http://www.scopus.com/inward/record.url?scp=79952003081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952003081&partnerID=8YFLogxK

U2 - 10.1038/oby.2010.245

DO - 10.1038/oby.2010.245

M3 - Article

C2 - 20948526

AN - SCOPUS:79952003081

VL - 19

SP - 492

EP - 499

JO - Obesity

JF - Obesity

SN - 1930-7381

IS - 3

ER -