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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

Effects of LF and HF diet feeding on fecal lipid contents.Fecal lipid quantities for WT and Plin2- mice fed LF (A) or HF (B) diets for four days. All values are means ± SD, N = 4 per group. P-values were determined using the unpaired t-test (Prism 6, GraphPad Prism).
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pone.0131944.g002: Effects of LF and HF diet feeding on fecal lipid contents.Fecal lipid quantities for WT and Plin2- mice fed LF (A) or HF (B) diets for four days. All values are means ± SD, N = 4 per group. P-values were determined using the unpaired t-test (Prism 6, GraphPad Prism).

Mentions: HF diet feeding is associated with altered intestinal function [53,54]. Plin2 is abundantly expressed in the mouse intestinal epithelium and is hypothesized to contribute to lipid uptake properties of the intestinal mucosa [15]. To determine if Plin2 deletion influences intestinal lipid absorption functions in response to short-term changes in dietary fat content, we quantified TG levels in feces of WT and Plin2- mice after feeding LF or HF diets for four days. Fecal lipid contents of LF or HF fed WT mice were significantly lower than those of the corresponding Plin2- mice (Fig 2A and 2B).


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)

Effects of LF and HF diet feeding on fecal lipid contents.Fecal lipid quantities for WT and Plin2- mice fed LF (A) or HF (B) diets for four days. All values are means ± SD, N = 4 per group. P-values were determined using the unpaired t-test (Prism 6, GraphPad Prism).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131944.g002: Effects of LF and HF diet feeding on fecal lipid contents.Fecal lipid quantities for WT and Plin2- mice fed LF (A) or HF (B) diets for four days. All values are means ± SD, N = 4 per group. P-values were determined using the unpaired t-test (Prism 6, GraphPad Prism).
Mentions: HF diet feeding is associated with altered intestinal function [53,54]. Plin2 is abundantly expressed in the mouse intestinal epithelium and is hypothesized to contribute to lipid uptake properties of the intestinal mucosa [15]. To determine if Plin2 deletion influences intestinal lipid absorption functions in response to short-term changes in dietary fat content, we quantified TG levels in feces of WT and Plin2- mice after feeding LF or HF diets for four days. Fecal lipid contents of LF or HF fed WT mice were significantly lower than those of the corresponding Plin2- mice (Fig 2A and 2B).

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