Growth hormone receptor knockout (GHRKO) mice are smaller, long living, and have an increased metabolic rate compared with normal (N) littermates. However, it is known that thermoneutral conditions (30-32°C) elicit metabolic adaptations in mice, increasing the metabolic rate. Therefore, we hypothesized that environmental temperature would affect the expression profile of different adipose tissue depots in GHRKO mice. For this, N (n = 12) and GHRKO (n = 11) male mice were maintained at 23 or 30°C from weaning until 11 months of age. RNA sequencing from adipose tissue depots (epididymal-eWAT, perirenal-pWAT, subcutaneous-sWAT, and brown fat-BAT) was performed. Thermoneutrality increased body weight gain in GHRKO mice, but not in N mice. Only a few genes were commonly regulated by temperature in N and GHRKO mice. The BAT was the most responsive to changes in temperature in both N and GHRKO mice. BAT Ucp1 and Ucp3 expression were decreased to a similar extent in both N and GHRKO mice under thermoneutrality. In contrast, eWAT was mostly unresponsive to changes in temperature. The response to thermoneutrality in GHRKO mice was most divergent from N mice in sWAT. Relative weight of sWAT was almost 4 times greater in GHRKO mice. Very few genes were regulated in N mice sWAT when compared with GHRKO mice. This suggests that this WAT depot has a central role in the adaptation of GHRKO mice to changes in temperature.



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