Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo

Abstract

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 mumol/min) and release of glycerol (0.9 and 1.2 mumol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 mumol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI

“…In addition, the detection of BAT by 18 FDG-PET is performed indirectly, through measurements of BAT uptake of glucose, which is not the primary fuel for BAT thermogenesis. Heat production in BAT is primarily fueled by oxidation of fatty acids released from triglycerides stored in the intracellular fat droplets (10), and, as such, measurements of exogenous glucose or exogenous fatty acid uptake are clearly intrinsically insensitive to BAT thermogenic activity (11,12).…”

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

“…In this tissue, whose primary function is to produce heat for thermoregulation in human newborns and small mammals, it has long been known that much of the fuel for thermogenesis also derives from glucose being first converted to lipids before being oxidized. [70][71][72][73] More direct evidence that de novo lipogenesis is in fact critical for brown adipose tissue thermogenesis can be derived from recent studies in cold-exposed mice indicating that pharmacological suppression of de novo lipogenesis leads to marked reductions in brown adipose tissue thermal response to noradrenaline infusion (despite normal UCP1 levels) and resulted in the development of hypothermia. 74 One can therefore also refer to thermogenesis in brown adipose tissue as dependent upon substrate cycling between de novo lipogenesis and lipid oxidation, but whose rate is greatly amplified under sympathetic activation of mitochondrial proton leak in this tissue.…”

Rorα deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue

“…This has the consequence of raising the core body temperature. In cold-acclimated rodents, norepinephrine stimulates glucose uptake in brown adipose (22).Serendipitously, the diagnostic use of PET/CT scanning of human patients has identified depots of active beige fat [and more recently, also of brown adipose (7,15,20)] in sites in the neck and subclavicular area and along the spinal cord by enhanced uptake of the glucose analog [18F]deoxy-D-glucose at these sites (27). The uptake of brown/beige fat in humans is also dependent on cold exposure and adiposity, thus implying that similar processes may be operating in humans to regulate energy expenditure (34,35).…”

“…This has the consequence of raising the core body temperature. In cold-acclimated rodents, norepinephrine stimulates glucose uptake in brown adipose (22).…”