title: Diet-Induced Obesity and Its Differential Impact on Periodontal Bone Loss.
abstract: Obesity is associated with abnormal lipid metabolism and impaired bone homeostasis. The aim of our study was to investigate the impact of specific elevated fatty acid (FA) levels on alveolar bone loss in a Porphyromonas gingivalis-induced model of periodontal disease and to analyze underlying cellular mechanisms in bone-resorbing osteoclasts and bone-forming osteoblasts in mice. Four-week-old male C57BL/6 mice were randomly divided in groups and subjected to a palmitic acid (PA)- or oleic acid (OA)-enriched high-fat diet (HFD) (20% of calories from FA) or a normal caloric diet (C group) (10% of calories from FA) for 16 wk. Starting at week 10, mice were infected orally with P. gingivalis (W50) or placebo to induce alveolar bone loss. Animals were sacrificed, and percentage fat, serum inflammation (tumor necrosis factor [TNF]-α), and bone metabolism (osteocalcin [OC], carboxy-terminal collagen crosslinks [CTX], and N-terminal propeptides of type I procollagen [P1NP]) markers were measured. Osteoblasts and osteoclasts were cultured in the presence of elevated PA or OA levels and exposed to P. gingivalis. Animals on FA-enriched diets weighed significantly more compared with animals on a normal caloric diet (P < 0.05). Both obese groups had similar percentages of fat (P = nonsignificant); however, alveolar bone loss was significantly greater in animals that were on the PA-enriched HFD (P < 0.05). TNF-α levels were highest in the PA group (P < 0.001) and increased in all groups in response to P. gingivalis inoculation (P < 0.01), whereas bone remodeling markers OC, CTX, and P1NP were lowest in the PA group (P < 0.001) and highest in the C group. Bacterial challenge decreased bone metabolism markers in all groups (P < 0.01). Further, osteoclasts showed an augmented inflammatory response to P. gingivalis in the presence of hyperlipidemic PA levels as opposed to OA cultures, which responded similarly to controls. These findings indicate that the specific FA profile of diet rather than weight gain and obesity alone modulates bone metabolism and can therefore influence alveolar bone loss.
authors.affiliation: Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA Institute of Human Nutrition, Columbia University, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Muluke
authors.affiliation: Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA Institute of Human Nutrition, Columbia University, New York, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Gold
authors.affiliation: Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA Institute of Human Nutrition, Columbia University, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kiefhaber
authors.affiliation: Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Al-Sahli
authors.affiliation: Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Celenti
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, USA.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cremers
authors.affiliation: The Forsyth Institute, Boston, MA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Van Dyke
authors.affiliation: Division of Periodontics, Columbia University College of Dental Medicine, New York, NY, USA us2141@cumc.columbia.edu.
authors.forename: U
authors.initials: U
authors.lastname: Schulze-Späte
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology* / Q000276:immunology / Q000382:microbiology; D000818:Animals; D001835:Body Weight; D016723:Bone Remodeling / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D019301:Oleic Acid / Q000097:blood / Q000494:pharmacology; D010006:Osteoblasts / Q000276:immunology / Q000382:microbiology; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000276:immunology / Q000382:microbiology; D019308:Palmitic Acid / Q000097:blood / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D010919:Placebos; D016966:Porphyromonas gingivalis / Q000502:physiology; D011347:Procollagen / Q000097:blood; D011897:Random Allocation; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D024042:Collagen Type I; D015850:Interleukin-6; D010446:Peptide Fragments; D010455:Peptides; D010919:Placebos; D011347:Procollagen; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D019301:Oleic Acid; D019308:Palmitic Acid
keywords: bone metabolism; high-fat diet; inflammation; oleic acid; osteoclast; palmitic acid