Differential expression T4‐5’‐deiodinase activity in corpulent rats following cold exposure

Abstract

Multiple studies indicate that the thermic responses to diet and cold exposure may be impaired in obese rodents and are likely secondary to the combined contributions of sympathetic and thyroidal components of nonshivering thermogenesis (NST). T4 is normally deiodinated via outer ring deiodinase activity by D‐1 and/or D‐2 deiodinase activity to form hormonaly active T3 during fed and cold environments, or inner ring deiodinase activity via D‐3 to form reverse T3 (rT3) during food or energy deprivation. The effect of 14 hours of 4°C cold exposure on the obese phenotype of the LA/Ntul//‐cp rats was determined in normally reared young female animals 8 to 9 weeks of age and fed the Purina Chow #5012 ad libitum throughout. Body weights and adipose tissue mass were greater in the obese than the lean phenotype (p=<0.05). RMR and the dose related thermic responses to norepinephrine (NE, 200 ug., s.c.) were greater in lean than in obese. Cold exposure at 4°C resulted in decreases in rectal but not core temperature in obese rats, and the thermic responses to 45 minutes of 4°C cold exposure on VO2 were typical but were significantly greater in lean than obese animals at all time points measured. Circulating T4 concentrations were similar in lean and obese rats and serum T3 but not T4 concentrations increased dramatically in both phenotypes following the cold exposure, consistent with phenotype‐ and maximal IBAT‐linked changes in T4‐5’‐deiodinase activity / mg protein in kidney, liver and IBAT and in temperature linked increases in IBAT deiodinase activity / mg tissue protein in this strain. When D‐1 and D‐2 deiodinase activity was computed / tissue mass, further analysis indicated that D‐1 was the predominating deiodinase in liver, kidney, and gastrocnemius muscle, while in IBAT D‐2 > D‐1 activity / IBAT depot and was greater in obese than lean rats. Cold exposure was associated with modest increases in net kidney deiodinase activity only in kidney. Thus, the cold induced increases in circulating T3 in lean and obese rats are likely attributed at least in part to modest increases in renal T4‐5’ D‐2 deiodinase activity, in addition to maximal rates of conversion in other tissues in possible combination with decreases in hormone clearance rates during cold induced stress.