title: Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.
abstract: Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.
authors.affiliation: Division of Periodontics, College of Dental Medicine, Columbia University, 630 W 168th St, PH7C-200B, New York, NY, 10032, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Alsahli
authors.affiliation: Division of Periodontics, College of Dental Medicine, Columbia University, 630 W 168th St, PH7C-200B, New York, NY, 10032, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kiefhaber
authors.affiliation: Division of Periodontics, College of Dental Medicine, Columbia University, 630 W 168th St, PH7C-200B, New York, NY, 10032, USA.
authors.forename: Tziporah
authors.initials: T
authors.lastname: Gold
authors.affiliation: Division of Periodontics, College of Dental Medicine, Columbia University, 630 W 168th St, PH7C-200B, New York, NY, 10032, USA.
authors.forename: Munira
authors.initials: M
authors.lastname: Muluke
authors.affiliation: Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, NY, USA.
authors.forename: Hongfeng
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: Serge
authors.initials: S
authors.lastname: Cremers
authors.affiliation: Division of Periodontics, College of Dental Medicine, Columbia University, 630 W 168th St, PH7C-200B, New York, NY, 10032, USA. us2141@cumc.columbia.edu.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schulze-Späte
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers; D002518:Ceramides / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D019308:Palmitic Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D002518:Ceramides; D019301:Oleic Acid; D019308:Palmitic Acid; C097760:N-palmitoylsphingosine
keywords: Ceramides; Mineralization; Obesity; Osteoblast; Palmitic acid