Altered metabolism and lipodystrophy in the early B-cell factor 1-deficient mouse.
Document Type
Article
Publication Date
2010
Keywords
Adipose-Tissue, Animals, Blood-Glucose, Bone-Marrow, CCAAT-Enhancer-Binding-Protein-beta, Calorimetry, Energy-Metabolism, Glucagon, Insulin, Leptin, Lipid-Metabolism, Lipodystrophy, Mice-Knockout, PPAR-gamma, RNA-Messenger, Reverse-Transcriptase-Polymerase-Chain-Reaction, Statistics-Nonparametric, Trans-Activators
First Page
1611
Last Page
1621
JAX Source
Endocrinology 2010 Apr; 151(4):1611-21.
Abstract
We previously reported that mice deficient for the transcription factor early B-cell factor (Ebf1) exhibit markedly increased numbers of osteoblasts, bone formation rate, and serum osteocalcin, but the bone marrow of Ebf1(-/-) mice is also striking in its increased marrow adiposity. The purpose of this work was to analyze the metabolic phenotype that accompanies the altered bone morphology of Ebf1(-/-) mice. Whereas marrow adiposity was increased, deposition of white adipose tissue in other regions of the body was severely reduced (sc 40-50%, abdominally 80-85%). Brown adipose exhibited decreased lipid deposition. Subcutaneous and perigonadal white adipose tissue showed a decrease in mRNA transcripts for peroxisomal proliferator-activated receptor-gamma2 and CCAAT/enhancer-binding protein-beta in Ebf1(-/-) tissue compared with wild type. Circulating levels of leptin were decreased in Ebf1(-/-) animals compared with their littermate controls (down 65-95%), whereas adiponectin remained comparable after 2 wk of age. Serum analysis also found the Ebf1(-/-) animals were hypoglycemic and hypotriglyceridemic. After ip injection of insulin, the serum glucose levels in Ebf1(-/-) mice took longer to recover, and after a glucose challenge the Ebf1(-/-) animals reached serum glucose levels almost twice that of their wild-type counterparts. Measurement of circulating pancreatic hormones revealed normal or reduced insulin levels in the Ebf1(-/-) mice, whereas glucagon was significantly increased (up 1.7- to 8.5-fold). Metabolically the Ebf1(-/-) mice had increased O(2) consumption, CO(2) production, food and water intake, and activity. Markers for gluconeogenesis, however, were decreased in the Ebf1(-/-) mice compared with controls. In conclusion, the Ebf1-deficient animals exhibit defects in adipose tissue deposition with increased marrow adiposity and impaired glucose mobilization.
Recommended Citation
Fretz JA,
Nelson T,
Xi Y,
Adams DJ,
Rosen CJ,
Horowitz MC.
Altered metabolism and lipodystrophy in the early B-cell factor 1-deficient mouse. Endocrinology 2010 Apr; 151(4):1611-21.