Brown-adipose-tissue lipogenesis in starvation: effects of insulin and (-) hydroxycitrate

Glucose or insulin increased lipogenesis (measured in vivo using 3H2O) in brown fat of starved rats. Such increases were associated with activation of pyruvate dehydrogenase and increased use of glucose as a lipogenic precursor (monitored as an increase in the 14C/3H ratio in brown-fat fatty acids in rats injected with both 3H20 and [U-14C]glucose). (-) Hydroxycitrate did not inhibit basal rates of brown-fat lipogenesis in starved rats but suppressed the increases in lipogenesis and glucose utilization observed in response to insulin. (-)Hydroxycitrate did not, however, inhabit the increase in 14C/3H observed after insulin treatment. The results indicate that in brown fat, glucose is utilized for fatty-acid synthesis predominantly via citrate, and that insulin acts to increase lipogenesis at site(s) prior to citrate cleavage. As basal rates of lipogenesis were not inhibited by (-)hydroxycitrate, it is suggested that acetate may be a lipogenic substrate for brown fat in starvation, and experiments are described which support this suggestion.