3-hydroxybutyrate inhibits noradrenaline-induced thermogenesis in lean but not in obese Zucker rats

Abstract

OBJECTIVE: To determine the effect of 3-hydroxybutyrate (3OHB) on the thermogenic response to noradrenaline (NA) in lean and genetically obese Zucker fa/fa rats.

DESIGN: Rats were infused with 18.7 nmol·kg⁻¹·min⁻¹ of NA, supplemented, for 15 min, with 66.7 μmol·kg⁻¹·min⁻¹ of R-3-hydroxybutyrate (3OHB).

SUBJECTS: Pentobarbital-anaesthetized lean and obese Zucker rats.

MEASUREMENTS: Aortic and interscapular brown adipose tissue (BAT) temperature; plasma NA, 3OHB, glucose and insulin levels during infusion.

RESULTS: The NA-induced increase in aortic and BAT temperature was more marked in lean than in obese rats. In lean rats, the rise was arrested by 3OHB; but in obese rats 3OHB had no effect. Infusion of saline, glucose or 3OHB in the absence of NA did not induce changes in either temperature. NA infusion resulted in a rapid increase in plasma NA to 45–50 nM in both groups; this plateau was maintained for up to 60 min. The presence of 3OHB decreased the plasma NA of lean rats, but did not affect the plasma NA of the obese rats. Blood 3OHB rose to 1.2 mM during 3OHB infusion in both groups, and decreased on cessation of infusion. Blood glucose levels increased with NA infusion in both groups; the presence of high 3OHB levels decreased glucose levels only in lean rats.

CONCLUSION: The changes in NA levels induced by 3OHB may help explain the effects observed on temperature and glucose. The defective thermogenic system of obese rats cannot be modulated by 3OHB, unlike thermogenesis in lean rats, on which 3OHB has a marked effect.