Growth Hormone Signaling Shapes the Impact of Environmental Temperature on Transcriptomic Profile of Different Adipose Tissue Depots in Male Mice

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 degrees 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 degrees 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.

Automated summary

The expression profile of different adipose tissue depots in GHRKO mice is affected by environmental temperature, with brown adipose tissue (BAT) being the most responsive. BAT Ucp1 and Ucp3 expression decreases under thermoneutral conditions in both normal (N) and GHRKO mice. In contrast, subcutaneous white adipose tissue (sWAT) shows the most divergent response to thermoneutrality in GHRKO mice compared to N mice.