To determine the relative importance of TSH in white adipose tissue, we compared 
the adipose phenotypes of two distinct mouse models of hypothyroidism. These 
models differed in that the normal reciprocal relationship between thyroid 
hormone and TSH was intact in one and disrupted in the other. One model, 
thyroidectomized (THYx) mice, had a 100-fold increase in TSH and a normal TSH 
receptor (TSHR); in contrast, the other model, hyt/hyt mice, had a 120-fold 
elevation of TSH but a nonfunctional TSHR. Although both THYx and hyt/hyt mice 
were in a severe hypothyroid state, the epididymal fat (mg)/body wt (g) (F/B) 
ratio of THYx mice was much smaller than that of hyt/hyt mice (8.2 ± 0.43 vs. 
14.4 ± 0.40, respectively, P < 0.001). The fat cell diameter in THYx mice was 
also smaller than that in hyt/hyt mice (79 ± 2.8 vs. 105 ± 2.2 μm, respectively, 
P < 0.001), suggesting that TSH induced lipolysis in adipose tissues. When we 
transferred a functional mouse TSHR gene and a control plasmid into opposite 
sides of epididymal fat of hyt/hyt mice by plasmid injection combined with 
electroporation, fat weight of the TSHR side was decreased to 60% of that of the 
control side. Messenger RNA levels of hormone-sensitive lipase in epididymal fat 
containing the transferred TSHR gene were twofold higher than those in tissue 
from the control side. These results indicated that TSH worked as a lipolytic 
factor in white adipose tissues, especially in mice in a hypothyroid state.