Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice

Sophie A.H. Jacobs, Eveline Gart, Debby Vreeken, Bart A.A. Franx, Lotte Wekking, Vivienne G.M. Verweij, Nicole Worms, Marieke H. Schoemaker, Gabriele Gross, Martine C. Morrison, Robert Kleemann, Ilse A.C. Arnoldussen, Amanda J. Kiliaan

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity. METHODS: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI. RESULTS: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity. CONCLUSIONS: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.

Original languageEnglish
JournalNutrients
Volume11
Issue number8
DOIs
Publication statusPublished - 10 Aug 2019

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fatty liver
High Fat Diet
high fat diet
Sex Characteristics
Fats
brain
gender
mice
Brain
lipids
Obesity
Liver
obesity
Adipose Tissue
adipose tissue
liver
Cerebrovascular Circulation
Pathology
Inflammation
inflammation

Keywords

  • juvenile
  • obesity
  • sex

Cite this

Jacobs, Sophie A.H. ; Gart, Eveline ; Vreeken, Debby ; Franx, Bart A.A. ; Wekking, Lotte ; Verweij, Vivienne G.M. ; Worms, Nicole ; Schoemaker, Marieke H. ; Gross, Gabriele ; Morrison, Martine C. ; Kleemann, Robert ; Arnoldussen, Ilse A.C. ; Kiliaan, Amanda J. / Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice. In: Nutrients. 2019 ; Vol. 11, No. 8.
@article{3309bc47289040b693bbe1293eb12621,
title = "Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice",
abstract = "BACKGROUND: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity. METHODS: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI. RESULTS: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity. CONCLUSIONS: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.",
keywords = "juvenile, obesity, sex",
author = "Jacobs, {Sophie A.H.} and Eveline Gart and Debby Vreeken and Franx, {Bart A.A.} and Lotte Wekking and Verweij, {Vivienne G.M.} and Nicole Worms and Schoemaker, {Marieke H.} and Gabriele Gross and Morrison, {Martine C.} and Robert Kleemann and Arnoldussen, {Ilse A.C.} and Kiliaan, {Amanda J.}",
year = "2019",
month = "8",
day = "10",
doi = "10.3390/nu11081861",
language = "English",
volume = "11",
journal = "Nutrients",
issn = "2072-6643",
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Jacobs, SAH, Gart, E, Vreeken, D, Franx, BAA, Wekking, L, Verweij, VGM, Worms, N, Schoemaker, MH, Gross, G, Morrison, MC, Kleemann, R, Arnoldussen, IAC & Kiliaan, AJ 2019, 'Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice' Nutrients, vol. 11, no. 8. https://doi.org/10.3390/nu11081861

Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice. / Jacobs, Sophie A.H.; Gart, Eveline; Vreeken, Debby; Franx, Bart A.A.; Wekking, Lotte; Verweij, Vivienne G.M.; Worms, Nicole; Schoemaker, Marieke H.; Gross, Gabriele; Morrison, Martine C.; Kleemann, Robert; Arnoldussen, Ilse A.C.; Kiliaan, Amanda J.

In: Nutrients, Vol. 11, No. 8, 10.08.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice

AU - Jacobs, Sophie A.H.

AU - Gart, Eveline

AU - Vreeken, Debby

AU - Franx, Bart A.A.

AU - Wekking, Lotte

AU - Verweij, Vivienne G.M.

AU - Worms, Nicole

AU - Schoemaker, Marieke H.

AU - Gross, Gabriele

AU - Morrison, Martine C.

AU - Kleemann, Robert

AU - Arnoldussen, Ilse A.C.

AU - Kiliaan, Amanda J.

PY - 2019/8/10

Y1 - 2019/8/10

N2 - BACKGROUND: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity. METHODS: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI. RESULTS: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity. CONCLUSIONS: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.

AB - BACKGROUND: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity. METHODS: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI. RESULTS: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity. CONCLUSIONS: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.

KW - juvenile

KW - obesity

KW - sex

U2 - 10.3390/nu11081861

DO - 10.3390/nu11081861

M3 - Article

VL - 11

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 8

ER -