title: Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet.
abstract: Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH.
authors: 1] Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea [2] Department of Sports Medicine, Taishan Medical University, Shandong, China.
authors: Lu
authors: L
authors: Zhou
authors: Department of Pathology, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Kyu Yun
authors: KY
authors: Jang
authors: Department of Biochemistry, Chonbuk National University Medical School, Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors: Young Jae
authors: YJ
authors: Moon
authors: Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Sajeev
authors: S
authors: Wagle
authors: Department of Pathology, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Kyoung Min
authors: KM
authors: Kim
authors: Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Kwang Bok
authors: KB
authors: Lee
authors: Department of Biochemistry, Chonbuk National University Medical School, Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors: Byung-Hyun
authors: BH
authors: Park
authors: Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute for Endocrine Sciences and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors: Jung Ryul
authors: JR
authors: Kim
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005270:Femur Head / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D005271:Femur Head Necrosis / Q000235:genetics / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007275:Injections, Intravenous; D020738:Leptin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020738:Leptin; C493717:Runx2 protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat