title: Morbid obesity attenuates the skeletal abnormalities associated with leptin deficiency in mice.
abstract: Leptin-deficient ob/ob mice are morbidly obese and exhibit low total bone mass and mild osteopetrosis. In order to disassociate the skeletal effects of leptin deficiency from those associated with morbid obesity, we evaluated bone mass, architecture, gene expression, and indices of bone turnover in WT mice, ob/ob mice allowed to feed ad libitum (ob/ob), and ob/ob mice pair-fed equivalent to WT mice (pair-fed ob/ob). Mice were maintained at 32 °C (thermoneutral) from 6 to 18 weeks of age to minimize differences in resting energy expenditure. ob/ob mice were heavier, had more abdominal white adipose tissue (WAT), and were hyperglycemic compared with WT mice. Femur length, bone mineral content (BMC) and bone mineral density, and midshaft femur cortical thickness were lower in ob/ob mice than in WT mice. Cancellous bone volume (BV) fraction was higher but indices of bone formation and resorption were lower in ob/ob mice compared with WT mice; reduced bone resorption in ob/ob mice resulted in pathological retention of calcified cartilage. Pair-fed ob/ob mice were lighter and had lower WAT, uterine weight, and serum glucose than ob/ob mice. Similarly, femoral length, BMC, and cortical thickness were lower in pair-fed ob/ob mice compared with ob/ob mice, as were indices of cancellous bone formation and resorption. In contrast, bone marrow adiposity, calcified cartilage, and cancellous BV fraction were higher at one or more cancellous sites in pair-fed ob/ob mice compared with ob/ob mice. These findings indicate that the skeletal abnormalities caused by leptin deficiency are markedly attenuated in morbidly obese ob/ob mice.
authors.affiliation: Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Russell T
authors.initials: RT
authors.lastname: Turner
authors.affiliation: Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Philbrick
authors.affiliation: Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Wong
authors.affiliation: Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Olson
authors.affiliation: Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Branscum
authors.affiliation: Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA Skeletal Biology LaboratorySchool of Biological and Population Health SciencesCenter for Healthy Aging ResearchBiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USA urszula.iwaniec@oregonstate.edu.
authors.forename: Urszula T
authors.initials: UT
authors.lastname: Iwaniec
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D015519:Bone Density; D001842:Bone and Bones / Q000002:abnormalities* / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D004435:Eating / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D020738:Leptin / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008820:Mice, Obese; D009767:Obesity, Morbid / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000235:genetics; D010455:Peptides / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia / Q000002:abnormalities / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D024042:Collagen Type I; D020738:Leptin; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin
keywords: dual-energy absorptiometry; histomorphometry; microcomputed tomography; obesity