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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

Metabolic effects of four-day LF and HF feeding on WT and Plin2- mice.(A) Body weights of eight-week-old WT and Plin2- fed the chow diet for 5 weeks (Initial) and after four days of LF (LFD Final) or HF (HFD Final) diet feeding. (B-D) Energy intake (B), energy expenditures (C) and energy balance (D) properties. (E) Representative H&E stained liver sections of LF and HF fed WT or Plin2- mice at 200X magnification. PT, portal triad. CV, central vein. (F,G) Average respiratory exchange ratios (RER) (F), and total activities (G) of WT and Pln2- mice fed LF or HF diets. Data were analyzed by 2-way ANOVA examining the effects of diet, genotype, and their interaction. Statistical significance of diet on each parameter is indicated in the respective figures. All values are means ± SEM, N = 4 per group.
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pone.0131944.g001: Metabolic effects of four-day LF and HF feeding on WT and Plin2- mice.(A) Body weights of eight-week-old WT and Plin2- fed the chow diet for 5 weeks (Initial) and after four days of LF (LFD Final) or HF (HFD Final) diet feeding. (B-D) Energy intake (B), energy expenditures (C) and energy balance (D) properties. (E) Representative H&E stained liver sections of LF and HF fed WT or Plin2- mice at 200X magnification. PT, portal triad. CV, central vein. (F,G) Average respiratory exchange ratios (RER) (F), and total activities (G) of WT and Pln2- mice fed LF or HF diets. Data were analyzed by 2-way ANOVA examining the effects of diet, genotype, and their interaction. Statistical significance of diet on each parameter is indicated in the respective figures. All values are means ± SEM, N = 4 per group.

Mentions: Our previous studies have documented that Plin2 expression is required for long-term weight gain, increased adiposity, and fatty liver formation in mice fed HF diets [13]. These initial studies suggested that the effects of Plin2 on these properties were mediated in part by its actions on energy intake and activity levels of HF fed mice. Because, HF diet feeding has also been shown to have acute effects on energy intake and metabolic properties of mice [51,52], we were interested in determining how Plin2 affects short-term responses to HF diet feeding. We addressed this question by placing 8 week-old congenic WT (C57B/6) and Plin2- male mice, which had been maintained since weaning on a mouse chow diet (16% kcal fat, 24% kcal protein, 60% kcal carbohydrate), in metabolic chambers and feeding them ad libitum with calorically equivalent LF (10% kcal fat, 20% kcal protein, 70% kcal carbohydrate) or HF (60% kcal fat, 20% kcal protein and 20% kcal carbohydrate) diets (Table 1) for four days. Data in Fig 1A show that during this period body weights of Plin2- mice did not change significantly on either diet. The body weights of WT mice did not change on the LF diet, but they increased about 10% (p<0.02) on the HF diet.


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)

Metabolic effects of four-day LF and HF feeding on WT and Plin2- mice.(A) Body weights of eight-week-old WT and Plin2- fed the chow diet for 5 weeks (Initial) and after four days of LF (LFD Final) or HF (HFD Final) diet feeding. (B-D) Energy intake (B), energy expenditures (C) and energy balance (D) properties. (E) Representative H&E stained liver sections of LF and HF fed WT or Plin2- mice at 200X magnification. PT, portal triad. CV, central vein. (F,G) Average respiratory exchange ratios (RER) (F), and total activities (G) of WT and Pln2- mice fed LF or HF diets. Data were analyzed by 2-way ANOVA examining the effects of diet, genotype, and their interaction. Statistical significance of diet on each parameter is indicated in the respective figures. All values are means ± SEM, N = 4 per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131944.g001: Metabolic effects of four-day LF and HF feeding on WT and Plin2- mice.(A) Body weights of eight-week-old WT and Plin2- fed the chow diet for 5 weeks (Initial) and after four days of LF (LFD Final) or HF (HFD Final) diet feeding. (B-D) Energy intake (B), energy expenditures (C) and energy balance (D) properties. (E) Representative H&E stained liver sections of LF and HF fed WT or Plin2- mice at 200X magnification. PT, portal triad. CV, central vein. (F,G) Average respiratory exchange ratios (RER) (F), and total activities (G) of WT and Pln2- mice fed LF or HF diets. Data were analyzed by 2-way ANOVA examining the effects of diet, genotype, and their interaction. Statistical significance of diet on each parameter is indicated in the respective figures. All values are means ± SEM, N = 4 per group.
Mentions: Our previous studies have documented that Plin2 expression is required for long-term weight gain, increased adiposity, and fatty liver formation in mice fed HF diets [13]. These initial studies suggested that the effects of Plin2 on these properties were mediated in part by its actions on energy intake and activity levels of HF fed mice. Because, HF diet feeding has also been shown to have acute effects on energy intake and metabolic properties of mice [51,52], we were interested in determining how Plin2 affects short-term responses to HF diet feeding. We addressed this question by placing 8 week-old congenic WT (C57B/6) and Plin2- male mice, which had been maintained since weaning on a mouse chow diet (16% kcal fat, 24% kcal protein, 60% kcal carbohydrate), in metabolic chambers and feeding them ad libitum with calorically equivalent LF (10% kcal fat, 20% kcal protein, 70% kcal carbohydrate) or HF (60% kcal fat, 20% kcal protein and 20% kcal carbohydrate) diets (Table 1) for four days. Data in Fig 1A show that during this period body weights of Plin2- mice did not change significantly on either diet. The body weights of WT mice did not change on the LF diet, but they increased about 10% (p<0.02) on the HF diet.

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