title: Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.
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 null 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-null 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.
authors.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.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Frank
authors.affiliation: Division of Basic Reproductive Sciences, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Elise S
authors.initials: ES
authors.lastname: Bales
authors.affiliation: Division of Basic Reproductive Sciences, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Monks
authors.affiliation: Division of Endocrinology and Metabolism, University of Colorado School of Medicine, Aurora, Colorado, United States of America; The Center for Human Nutrition, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Jackman
authors.affiliation: Division of Endocrinology and Metabolism, University of Colorado School of Medicine, Aurora, Colorado, United States of America; The Center for Human Nutrition, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Paul S
authors.initials: PS
authors.lastname: MacLean
authors.affiliation: Division of Infectious Disease, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Diana
authors.initials: D
authors.lastname: Ir
authors.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.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Robertson
authors.affiliation: Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Orlicky
authors.affiliation: Division of Basic Reproductive Sciences, University of Colorado School of Medicine, Aurora, Colorado, United States of America; The Center for Human Nutrition, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: James L
authors.initials: JL
authors.lastname: McManaman
mesh_terms: D050154:Adiposity / Q000502:physiology; D000818:Animals; D001835:Body Weight; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000070780:Perilipin-2; D012336:RNA, Ribosomal, 16S
chemical_list: D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D012336:RNA, Ribosomal, 16S