Abstract
Obesity is associated with chronic up‐regulation of inflammatory cytokines which stimulate osteoclast activity and bone resorption. Osteopenia or low bone mass is observed in a variety of physiological conditions with chronic inflammation including aging and post‐menopause with estrogen deficiency. This study investigated whether obesity induced by a high‐fat diet alters bone loss in an animal model of chronic inflammation with low‐dose, slow‐release of lipopolysaccharide (LPS). Forty‐eight 6‐wk‐old female C57BL/6 mice were randomly assigned to four treatment groups (n=12/group) in a 2×2 factorial design: control (placebo) or LPS treatment and fed either a normal‐fat (NF, 10% energy as fat) or a high‐fat (HF, 45% energy as fat) diet ad libitum for 3 mon. LPS (E‐coli serotype 0127:B8) was incorporated into time‐release pellets designed to provide a consistent dose (1.3μg/day) for 3 months The LPS and placebo (containing just biodegradable carrier binder) pellets were implanted subcutaneously in the dorsal region of the neck. Mice implanted with LPS had similar body weight, fat mass and lean mass to those in the placebo (NF + HF) groups. LPS treatment increased serum concentration of tartrate‐resistant acid phosphatase (TRAP, a bone resorption marker), expression of proinflammatory cytokines (TNF‐α and IL‐6) in abdominal adipose tissue, and bone marrow osteoclast differentiation, while decreasing tibial and vertebral trabecular bone volume, trabecular thickness, connectivity density, and bone mineral density (P < 0.05). Mice fed the HF diet had higher body weight (P < 0.05) mainly due to increased fat mass (P < 0.05) than animals fed the NF diet. Obesity induced by the HF diet increased serum TRAP concentration, bone marrow osteoclast differentiation, and expression of TNF‐α and IL‐6 in adipose tissue (P < 0.05). Compared to the NF groups, mice in the HF groups had decreased bone volume, connectivity density, trabecular number while had increased trabecular separation, and structure model index (P < 0.05). Mice implanted with LPS pellets and fed the high‐fat diet had the lowest bone mineral density compared to all other groups. These results show that obesity exacerbates bone loss in mice with chronic inflammation induced by low‐dose slow‐release LPS administration.Support or Funding Informationthe USDA Agricultural Research Service program “Bone Metabolism in Obesity,” Current Research Information System no. 5450‐51000‐046‐00D
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