TitleMorbid obesity attenuates the skeletal abnormalities associated with leptin deficiency in mice.
Publication TypeJournal Article
Year of Publication2014
AuthorsTurner, RT, Philbrick, KA, Wong, CP, Olson, DA, Branscum, AJ, Iwaniec, UT
JournalJ Endocrinol
Volume223
Issue1
PaginationM1-15
Date Published2014 Oct
ISSN1479-6805
KeywordsAdipose Tissue, White, Analysis of Variance, Animals, Blood Glucose, Body Weight, Bone and Bones, Bone Density, Collagen Type I, Eating, Female, Gene Expression Profiling, Leptin, Mice, Mice, Obese, Obesity, Morbid, Oligonucleotide Array Sequence Analysis, Osteocalcin, Osteogenesis, Peptides, Reverse Transcriptase Polymerase Chain Reaction, Tibia
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.

DOI10.1530/JOE-14-0224
Alternate JournalJ. Endocrinol.
PubMed ID24990938
PubMed Central IDPMC4161659
Grant ListR01 AR060913 / AR / NIAMS NIH HHS / United States