Reduced adiposity in ob/ob mice following total body irradiation and bone marrow transplantation.
OBJECTIVE
The objective of this study was to assess long-term metabolic consequences of total body irradiation (TBI) and bone marrow transplantation. Severe obesity develops due to both hypertrophy and hyperplasia of adipocytes. We hypothesized that TBI would arrest adipose tissue growth and would affect insulin resistance (IR).


METHODS
We exposed 2-month-old female ob/ob mice to 8 Grays of TBI followed by bone marrow transplantation and tested the animals for body weight (BW) gain, body composition, blood glucose, and insulin sensitivity.


RESULTS
Two months after TBI, irradiated mice stopped gaining BW, whereas non-treated mice continued to grow. At the age of 9.5 months, body mass of irradiated mice was 60.6 +/- 1.4 grams, which was only 61% of that in non-treated ob/ob controls (99.4 +/- 1.6 grams). Body composition measurements by DXA showed that decreased BW was primarily due to an impaired fat accumulation. This could not result from the production of leptin by bone marrow-derived adipocyte progenitors because inhibition of the obese phenotype was identical in recipients of both B6 and ob/ob bone marrow. Inability of the irradiated mice to accumulate fat was associated with hepatomegaly, lower levels of monocyte chemoattractant protein-1 expression in adipose tissue, and increased IR.


CONCLUSIONS
Our data argue in favor of the hypothesis that inability of adipose tissue to expand may increase IR. This mouse model may be valuable for studies of late-onset radiation-induced IR in humans.
Ablamunits
Vitaly
V
Obesity Research Center, St. Luke's Hospital, Room WH1020, 1111 Amsterdam Avenue, New York, NY 10025, USA. ablamunits@excite.com
Weisberg
Stuart P
SP
Lemieux
Jacob E
JE
Combs
Terry P
TP
Klebanov
Simon
S
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D052242:Adiponectin / Q000097:blood; D050154:Adiposity / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002452:Cell Count; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006529:Hepatomegaly / Q000209:etiology; D007333:Insulin Resistance / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D014916:Whole-Body Irradiation / Q000009:adverse effects
D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2