Dataset Information

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.

SUBMITTER: Jacobs SAH

PROVIDER: S-EPMC6723313 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

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 SAH Gart Eveline E Vreeken Debby D Franx Bart A A BAA Wekking Lotte L Verweij Vivienne G M VGM Worms Nicole N Schoemaker Marieke H MH Gross Gabriele G Morrison Martine C MC Kleemann Robert R Arnoldussen Ilse A C IAC Kiliaan Amanda J AJ

Nutrients 20190810 8

<h4>Background</h4>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 d ...[more]

PMID: 31405127

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Project description:BackgroundObesity frequently associates with the development of non-alcoholic fatty liver disease (NAFLD) and atherosclerosis. Chronic inflammation in white adipose tissue (WAT) seems to be an important driver of these manifestations.ObjectiveThis study investigated a combination of an extensively hydrolyzed casein (eHC), docosahexaenoic acid (DHA), arachidonic acid (ARA), and Lactobacillus Rhamnosus GG (LGG) (together referred to as nutritional ingredients, NI) on the development of obesity, metabolic risk factors, WAT inflammation, NAFLD and atherosclerosis in high-fat diet-fed LDLr-/-.Leiden mice, a model that mimics disease development in humans.MethodsLDLr-/-.Leiden male mice (n = 15/group) received a high-fat diet (HFD, 45 Kcal%) for 21 weeks with or without the NI (23.7% eHC, 0.083% DHA, 0.166% ARA; all w/w and 1x109 CFU LGG gavage 3 times/week). HFD and HFD+NI diets were isocaloric. A low fat diet (LFD, 10 Kcal%) was used for reference. Body weight, food intake and metabolic risk factors were assessed over time. At week 21, tissues were analyzed for WAT inflammation (crown-like structures), NAFLD and atherosclerosis. Effects of the individual NI components were explored in a follow-up experiment (n = 7/group).ResultsWhen compared to HFD control, treatment with the NI strongly reduced body weight to levels of the LFD group, and significantly lowered (P<0.01) plasma insulin, cholesterol, triglycerides, leptin and serum amyloid A (P<0.01). NI also reduced WAT mass and inflammation. Strikingly, NI treatment significantly reduced macrovesicular steatosis, lobular inflammation and liver collagen (P<0.05), and attenuated atherosclerosis development (P<0.01). Of the individual components, the effects of eHC were most pronounced but could not explain the entire effects of the NI formulation.ConclusionsA combination of eHC, ARA, DHA and LGG attenuates obesity and associated cardiometabolic diseases (NAFLD, atherosclerosis) in LDLr-/-.Leiden mice. The observed reduction of inflammation in adipose tissue and in the liver provides a rationale for these comprehensive health effects.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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