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Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

Frank DN, Bales ES, Monks J, Jackman MJ, MacLean PS, Ir D, Robertson CE, Orlicky DJ, McManaman JL - PLoS ONE (2015)

Bottom Line: Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function.Plin2- mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice.Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disease, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Microbiome Research Consortium, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

ABSTRACT
Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2- mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity.

No MeSH data available.


Related in: MedlinePlus

Influence of dietary fat and Plin2 genotype on fecal metagenomes.Metagenomic DNA reads were annotated against the KEGG orthology hierarchy [74] using MG-RAST[46] and significant KO categories identified as described in the text. The heatmaps display the normalized relative abundances of KO categories that varied significantly as a function of genotype combined with diet (Panel A), diet alone (Panel B), or genotype alone (Panel C). Unadjusted p-value cutoffs for each panel were chosen in order to display a representative selection of the data in a single figure.
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pone.0131944.g006: Influence of dietary fat and Plin2 genotype on fecal metagenomes.Metagenomic DNA reads were annotated against the KEGG orthology hierarchy [74] using MG-RAST[46] and significant KO categories identified as described in the text. The heatmaps display the normalized relative abundances of KO categories that varied significantly as a function of genotype combined with diet (Panel A), diet alone (Panel B), or genotype alone (Panel C). Unadjusted p-value cutoffs for each panel were chosen in order to display a representative selection of the data in a single figure.

Mentions: A total of 3874 KEGG ortholog (KO) functional classes were identified at least once in the combined metagenomic dataset. Of these, 27 KO categories differed significantly (p<0.01) when both diet (HF vs. LF) and genotype (Plin2- vs. WT) were combined into one predictor variable for Kruskal-Wallis tests (Fig 6A). Hierarchical clustering of animals based on KO frequency patterns among significant KO categories indicated that diet was a larger factor than genotype in determining fecal metagenome composition (Fig 6, Panel A). Regardless of genotype, HF and LF diets resulted in significant differences in the frequencies of multiple functional categories, which belonged primarily to the higher-order KO categories of “Metabolism”, “Cellular Processes”, and “Environmental Information Processing” (Fig 6A and 6B). A variety of metabolic functions, including those of amino acid, carbohydrate, cofactor, and xenobiotic metabolism, were identified through this analysis. Interestingly, only one KO, K03736 (ethanolamine ammonia-lyase small subunit [EC:4.3.1.7] belonging to the glycerophospholipid metabolism pathway ko00564), was associated with lipid metabolism. Nevertheless, 16 KO categories were found to differ significantly between Plin2- and WT animals. Again, these genes were associated primarily with carbohydrate and amino acid metabolism, along with environmental sensing (Fig 6A and 6C).


Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

Frank DN, Bales ES, Monks J, Jackman MJ, MacLean PS, Ir D, Robertson CE, Orlicky DJ, McManaman JL - PLoS ONE (2015)

Influence of dietary fat and Plin2 genotype on fecal metagenomes.Metagenomic DNA reads were annotated against the KEGG orthology hierarchy [74] using MG-RAST[46] and significant KO categories identified as described in the text. The heatmaps display the normalized relative abundances of KO categories that varied significantly as a function of genotype combined with diet (Panel A), diet alone (Panel B), or genotype alone (Panel C). Unadjusted p-value cutoffs for each panel were chosen in order to display a representative selection of the data in a single figure.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493139&req=5

pone.0131944.g006: Influence of dietary fat and Plin2 genotype on fecal metagenomes.Metagenomic DNA reads were annotated against the KEGG orthology hierarchy [74] using MG-RAST[46] and significant KO categories identified as described in the text. The heatmaps display the normalized relative abundances of KO categories that varied significantly as a function of genotype combined with diet (Panel A), diet alone (Panel B), or genotype alone (Panel C). Unadjusted p-value cutoffs for each panel were chosen in order to display a representative selection of the data in a single figure.
Mentions: A total of 3874 KEGG ortholog (KO) functional classes were identified at least once in the combined metagenomic dataset. Of these, 27 KO categories differed significantly (p<0.01) when both diet (HF vs. LF) and genotype (Plin2- vs. WT) were combined into one predictor variable for Kruskal-Wallis tests (Fig 6A). Hierarchical clustering of animals based on KO frequency patterns among significant KO categories indicated that diet was a larger factor than genotype in determining fecal metagenome composition (Fig 6, Panel A). Regardless of genotype, HF and LF diets resulted in significant differences in the frequencies of multiple functional categories, which belonged primarily to the higher-order KO categories of “Metabolism”, “Cellular Processes”, and “Environmental Information Processing” (Fig 6A and 6B). A variety of metabolic functions, including those of amino acid, carbohydrate, cofactor, and xenobiotic metabolism, were identified through this analysis. Interestingly, only one KO, K03736 (ethanolamine ammonia-lyase small subunit [EC:4.3.1.7] belonging to the glycerophospholipid metabolism pathway ko00564), was associated with lipid metabolism. Nevertheless, 16 KO categories were found to differ significantly between Plin2- and WT animals. Again, these genes were associated primarily with carbohydrate and amino acid metabolism, along with environmental sensing (Fig 6A and 6C).

Bottom Line: Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function.Plin2- mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice.Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Disease, University of Colorado School of Medicine, Aurora, Colorado, United States of America; Microbiome Research Consortium, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

ABSTRACT
Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2- mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity.

No MeSH data available.


Related in: MedlinePlus