Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation
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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.
KeywordsObesity Osteoblast Palmitic acid Ceramides Mineralization
Free fatty acid
High fathigh-fat diet
Procollagen type 1 N-terminal propeptide
Serine palmitoyl transferase 2
The study was supported by the National Institute of Dental and Craniofacial Research-K08DE018968 and by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1 TR000040.
Ulrike Schulze-Späte designed the study. Ahmad Alsahli, Kathryn Kiefhaber, Tziporah Gold, Munira Muluke, Hongfeng Jiang, and Serge Cremers contributed to experimental work and data analysis. Kathryn Kiefhaber and Ulrike Schulze-Späte prepared the first draft of the paper. Ahmad Alsahli, Kathryn Kiefhaber, Tziporah Gold, Munira Muluke, Hongfeng Jiang analyzed data, Ahmad Alsahli, Kathryn Kiefhaber, Tziporah Gold, Munira Muluke, Hongfeng Jiang, Serge Cremers, and Ulrike Schulze-Späte interpreted results, and Ulrike Schulze-Späte is guarantor. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.
Compliance with Ethical Standards
Conflict of Interest
The authors have no conflict of interest to declare.
Human and Animal Rights and Informed Consent
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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