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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

Microbiome composition and biodiversity are altered by genotype and diet.Fecal microbiomes from WT and Plin2- mice on standard chow, low fat (LF), and high fat (HF) diets were profiled by high-throughput 16S rRNA amplicons sequencing. Panel A displays the distributions of bacteria among phyla (left) and family-level taxonomic categories (right). For simplicity, only taxa with mean relative abundances >2% are displayed; numerical values are the median within-group abundances of taxa. Overall p-values (Poverall) were ascertained by non-parametric PERMANOVA tests for all six diet/genotype groups, using Morisita-Horn dissimilarity scores. PERMANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype). Significant results of pairwise PERMANOVA tests performed on each pair of genotype/diet groups are indicated by horizontal bars above each heatmap: •: p<0.1; *: p<0.05; **: p<0.01; ***: p<0.001. Panel B displays the differences in biodiversity indices (richness, evenness, and complexity) by genotype and diet categories. Overall p-values (Poverall) were ascertained by ANOVA tests for all six diet/genotype groups. ANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype).
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pone.0131944.g004: Microbiome composition and biodiversity are altered by genotype and diet.Fecal microbiomes from WT and Plin2- mice on standard chow, low fat (LF), and high fat (HF) diets were profiled by high-throughput 16S rRNA amplicons sequencing. Panel A displays the distributions of bacteria among phyla (left) and family-level taxonomic categories (right). For simplicity, only taxa with mean relative abundances >2% are displayed; numerical values are the median within-group abundances of taxa. Overall p-values (Poverall) were ascertained by non-parametric PERMANOVA tests for all six diet/genotype groups, using Morisita-Horn dissimilarity scores. PERMANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype). Significant results of pairwise PERMANOVA tests performed on each pair of genotype/diet groups are indicated by horizontal bars above each heatmap: •: p<0.1; *: p<0.05; **: p<0.01; ***: p<0.001. Panel B displays the differences in biodiversity indices (richness, evenness, and complexity) by genotype and diet categories. Overall p-values (Poverall) were ascertained by ANOVA tests for all six diet/genotype groups. ANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype).

Mentions: Because dietary fat content is a key regulator of gut microbiome composition [55], we next examined how altered intestinal lipid properties in Plin2- animals affected the gut microbiome. Significant differences in fecal microbiome composition (p = 0.02 for non-parametric PERMANOVA of family-level data [36]) were evident between chow fed WT and Plin2- mice at baseline (Day 0) prior to randomization to LF or HF diets (Fig 4A). At the phylum level, Plin2- mice harbored significantly greater relative abundances (RA) of Bacteroidetes at baseline compared with WT mice (51.1% vs. 47.7% RA; p = 0.05), whereas Firmicutes trended to lower RA in Plin2- mice (39.5% vs. 44.3% RA; p = 0.25). Within the phylum Bacteroidetes, Plin2- animals were enriched in the uncultured family S24-7 (36.8% vs. 25.7% RA; p = 0.05), whereas the family Bacteroidaceae was reduced (3.6% vs. 10.0% RA; p = 0.05) compared with WT animals. Likewise within the phylum Firmicutes, the family Ruminococcaceae was present at diminished levels in Plin2- mice (6.9% vs. 12.0%; p = 0.02).


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)

Microbiome composition and biodiversity are altered by genotype and diet.Fecal microbiomes from WT and Plin2- mice on standard chow, low fat (LF), and high fat (HF) diets were profiled by high-throughput 16S rRNA amplicons sequencing. Panel A displays the distributions of bacteria among phyla (left) and family-level taxonomic categories (right). For simplicity, only taxa with mean relative abundances >2% are displayed; numerical values are the median within-group abundances of taxa. Overall p-values (Poverall) were ascertained by non-parametric PERMANOVA tests for all six diet/genotype groups, using Morisita-Horn dissimilarity scores. PERMANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype). Significant results of pairwise PERMANOVA tests performed on each pair of genotype/diet groups are indicated by horizontal bars above each heatmap: •: p<0.1; *: p<0.05; **: p<0.01; ***: p<0.001. Panel B displays the differences in biodiversity indices (richness, evenness, and complexity) by genotype and diet categories. Overall p-values (Poverall) were ascertained by ANOVA tests for all six diet/genotype groups. ANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493139&req=5

pone.0131944.g004: Microbiome composition and biodiversity are altered by genotype and diet.Fecal microbiomes from WT and Plin2- mice on standard chow, low fat (LF), and high fat (HF) diets were profiled by high-throughput 16S rRNA amplicons sequencing. Panel A displays the distributions of bacteria among phyla (left) and family-level taxonomic categories (right). For simplicity, only taxa with mean relative abundances >2% are displayed; numerical values are the median within-group abundances of taxa. Overall p-values (Poverall) were ascertained by non-parametric PERMANOVA tests for all six diet/genotype groups, using Morisita-Horn dissimilarity scores. PERMANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype). Significant results of pairwise PERMANOVA tests performed on each pair of genotype/diet groups are indicated by horizontal bars above each heatmap: •: p<0.1; *: p<0.05; **: p<0.01; ***: p<0.001. Panel B displays the differences in biodiversity indices (richness, evenness, and complexity) by genotype and diet categories. Overall p-values (Poverall) were ascertained by ANOVA tests for all six diet/genotype groups. ANOVA using both diet and genotype as predictor variables was performed to calculate adjusted p-values (Pdiet and Pgenotype).
Mentions: Because dietary fat content is a key regulator of gut microbiome composition [55], we next examined how altered intestinal lipid properties in Plin2- animals affected the gut microbiome. Significant differences in fecal microbiome composition (p = 0.02 for non-parametric PERMANOVA of family-level data [36]) were evident between chow fed WT and Plin2- mice at baseline (Day 0) prior to randomization to LF or HF diets (Fig 4A). At the phylum level, Plin2- mice harbored significantly greater relative abundances (RA) of Bacteroidetes at baseline compared with WT mice (51.1% vs. 47.7% RA; p = 0.05), whereas Firmicutes trended to lower RA in Plin2- mice (39.5% vs. 44.3% RA; p = 0.25). Within the phylum Bacteroidetes, Plin2- animals were enriched in the uncultured family S24-7 (36.8% vs. 25.7% RA; p = 0.05), whereas the family Bacteroidaceae was reduced (3.6% vs. 10.0% RA; p = 0.05) compared with WT animals. Likewise within the phylum Firmicutes, the family Ruminococcaceae was present at diminished levels in Plin2- mice (6.9% vs. 12.0%; p = 0.02).

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