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Open AccessArticle

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

Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, 6500 HB Nijmegen, The Netherlands
Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, The Netherlands
Human and Animal Physiology, Wageningen University, 6700 AH Wageningen, The Netherlands
Reckitt Benckiser Health, Mead Johnson Pediatric Nutrition Institute, 6545 CJ Nijmegen, The Netherlands
Department of Vascular Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Nutrients 2019, 11(8), 1861;
Received: 24 June 2019 / Revised: 1 August 2019 / Accepted: 7 August 2019 / Published: 10 August 2019
(This article belongs to the Special Issue Diet, Lipid and Lipoprotein Metabolism and Human Health)
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. View Full-Text
Keywords: obesity; juvenile; sex obesity; juvenile; sex
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Jacobs, S.A.; Gart, E.; Vreeken, D.; Franx, B.A.; Wekking, L.; Verweij, V.G.; Worms, N.; Schoemaker, M.H.; Gross, G.; Morrison, M.C.; Kleemann, R.; Arnoldussen, I.A.; Kiliaan, A.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. Nutrients 2019, 11, 1861.

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