Dataset Information

Vitamin D₃ supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR^-/- and LDLR^+/+ mice.

ABSTRACT:

Introduction

Fatty liver disease is prevalent in populations with high caloric intake. Nutritherapeutic approaches are being considered, such as supplementary Vitamin D₃ , to improve aspects of metabolic syndrome, namely fatty liver disease, hyperlipidemia, and insulin resistance associated with obesity.

Methods

We analyzed female LDLR^-/- and LDLR^+/+ mice on a 10-week diabetogenic diet for markers of fatty liver disease, metabolic strain, and inflammation.

Results

The groups on a high fat high sugar diet with supplementary Vitamin D₃ , in comparison with the groups on a high fat high sugar diet alone, showed improved transaminase levels, significantly less hypertriglyceridemia and hyperinsulinemia, and histologically, there was less pericentral hepatic steatosis. Levels of non-esterified fatty acids and lipid peroxidation products were significantly lower in the group supplemented with additional Vitamin D₃ , as were systemic markers of inflammation (serum endotoxin and IL-6). M2 macrophage phenotype predominated in the group supplemented with additional Vitamin D₃ . Beneficial changes were observed as early as five weeks' supplementation with Vitamin D₃ and extended to restoration of high fat high sugar diet induced decrease of bone mineral density.

Conclusion

In summary, Vitamin D₃ was a significantly beneficial dietary additive to blunt a prediabetic phenotype in diet-induced obesity of female LDLR^-/- and LDLR^+/+ mice.

SUBMITTER: Kheder R

PROVIDER: S-EPMC5418139 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Vitamin D<sub>3</sub> supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR<sup>-/-</sup> and LDLR<sup>+/+</sup> mice.

Kheder Ramiar R Hobkirk James J Saeed Zeayd Z Janus Justyna J Carroll Sean S Browning Michael J MJ Stover Cordula C

Immunity, inflammation and disease 20170313 2

<h4>Introduction</h4>Fatty liver disease is prevalent in populations with high caloric intake. Nutritherapeutic approaches are being considered, such as supplementary Vitamin D<sub>3</sub> , to improve aspects of metabolic syndrome, namely fatty liver disease, hyperlipidemia, and insulin resistance associated with obesity.<h4>Methods</h4>We analyzed female LDLR<sup>-/-</sup> and LDLR<sup>+/+</sup> mice on a 10-week diabetogenic diet for markers of fatty liver disease, metabolic strain, and infla ...[more]

PMID: 28474500

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Project description:BACKGROUND:Insulin resistance underlies metabolic syndrome and is associated with excess adiposity and visceral fat accumulation, which is more frequently observed in males than females. However, in young females, the prevalence of metabolic syndrome is rising, mainly driven by accumulation of abdominal visceral fat. The degree to which sex-related differences could influence the development of insulin resistance remains unclear, and studies of potential therapeutic strategies to combat metabolic syndrome using rodent models have focused predominantly on males. We therefore evaluated the effects of two nutritional supplements derived from botanical sources, an extract of Artemisia dracunculus L. (termed PMI5011) and Momordica charantia (commonly known as bitter melon), on female mice challenged with a high-fat diet in order to determine if dietary intake of these supplements could ameliorate obesity-induced insulin resistance and metabolic inflexibility in skeletal muscle. METHODS:Body composition, physical activity and energy expenditure, fatty acid oxidation, insulin signaling, and gene and protein expression of factors controlling lipid metabolism and ectopic lipid accumulation were evaluated in female mice fed a high-fat diet supplemented with either PMI5011 or bitter melon. Statistical significance was assessed by unpaired two-tailed t test and repeated measures ANOVA. RESULTS:PMI5011 supplementation resulted in increased body weight and adiposity, while bitter melon did not induce changes in these parameters. Pyruvate tolerance testing indicated that both supplements increased hepatic glucose production. Both supplements induced a significant suppression in fatty acid oxidation in skeletal muscle homogenates treated with pyruvate, indicating enhanced metabolic flexibility. PMI5011 reduced lipid accumulation in skeletal muscle, while bitter melon induced a downward trend in lipid accumulation in the skeletal muscle and liver. This was accompanied by transcriptional regulation of autophagic genes by bitter melon in the liver. CONCLUSIONS:Data from the current study indicates that dietary supplementation with PMI5011 and bitter melon evokes a divergent, and generally less favorable, set of metabolic responses in female mice compared to effects previously observed in males. Our findings underscore the importance of considering sex-related variations in responses to dietary supplementation aimed at combating metabolic syndrome.

Project description:Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models. Here, we evaluate the impact of genetic risk factors on late-onset AD (LOAD) in mice fed with a high fat/high sugar diet (HFD). We focused on three mouse models created through the IU/JAX/PITT MODEL-AD Center. These included a combined risk model with APOE4 and a variant in triggering receptor expressed on myeloid cells 2 (Trem2R47H ). We have termed this model, LOAD1. Additional variants including the M28L variant in phospholipase C Gamma 2 (Plcg2M28L ) and the 677C > T variant in methylenetetrahydrofolate reductase (Mthfr 677C > T ) were engineered by CRISPR onto LOAD1 to generate LOAD1.Plcg2M28L and LOAD1.Mthfr 677C > T . At 2 months of age, animals were placed on an HFD that induces obesity or a control diet (CD), until 12 months of age. Throughout the study, blood was collected to assess the levels of cholesterol and glucose. Positron emission tomography/computed tomography (PET/CT) was completed prior to sacrifice to image for glucose utilization and brain perfusion. After the completion of the study, blood and brains were collected for analysis. As expected, animals fed a HFD, showed a significant increase in body weight compared to those fed a CD. Glucose increased as a function of HFD in females only with cholesterol increasing in both sexes. Interestingly, LOAD1.Plcg2M28L demonstrated an increase in microglia density and alterations in regional brain glucose and perfusion on HFD. These changes were not observed in LOAD1 or LOAD1.Mthfr 677C > T animals fed with HFD. Furthermore, LOAD1.Plcg2M28L but not LOAD1.Mthfr 677C > T or LOAD1 animals showed transcriptomics correlations with human AD modules. Our results show that HFD affects the brain in a genotype-specific manner. Further insight into this process may have significant implications for the development of lifestyle interventions for the treatment of AD.

Dataset Information

Vitamin D₃ supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR^-/- and LDLR^+/+ mice.

Introduction

Methods

Results

Conclusion

Publications

Vitamin D<sub>3</sub> supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR<sup>-/-</sup> and LDLR<sup>+/+</sup> mice.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Vitamin D3 supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR-/- and LDLR+/+ mice.

Introduction

Methods

Results

Conclusion

Publications

Vitamin D<sub>3</sub> supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR<sup>-/-</sup> and LDLR<sup>+/+</sup> mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Vitamin D₃ supplementation of a high fat high sugar diet ameliorates prediabetic phenotype in female LDLR^-/- and LDLR^+/+ mice.