Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline

Abstract

Cardiac output (CO) and the fractional distribution (FD) of γ-labeled plastic microspheres (15 ± 5 μm) injected into the left ventricle were used to calculate blood flow to organs and tissues of barbital-sedated warm-acclimated (WA) or cold-acclimated (CA) white rats at rest and then during their maximal calorigenic response to infused noradrenaline (NA). Flow to the major masses of brown adipose tissue (BAT) increased in WA rats from a mean of 0.81 ml/min (0.92% of CO) at rest to 13.5 ml/min (11.4% of CO) during calorigenesis; it increased in CA rats from 2.3 ml/min (2.6% of CO) to 57.2 ml/min (33.5% of CO). Flow to skeletal muscle increased in WA rats from 12.0 ml/min at rest to 15.1 ml/min during calorigenesis; it increased in CA rats from 9.9 ml/min to 14.5 ml/min. Flow to heart and to muscles involved in respiratory movements was two to five times greater during calorigenesis. Flow to most other tissues and organs increased or decreased by less than 40%.Arteriovenous differences in blood oxygen [Formula: see text] across interscapular BAT (IBAT) during rest and during calorigenesis together with measurements of blood flow established that IBAT alone accounted for 14% of the extra O2 used by CA rats during NA-induced calorigenesis. If during calorigenesis other masses of BAT have an [Formula: see text] as great as that for IBAT, the major masses of BAT together would account for 60% of the calorigenic response of the CA rat. In contrast, even if the skeletal muscle of the CA rat used all the O2 in the blood flowing through it during calorigenesis, it could not have been responsible for more than 12% of the calorigenic response.The rat, long considered to exemplify major participation of skeletal muscle in nonshivering thermogenesis (NST), now becomes just one of a growing list of species for which there is explicit or circumstantial evidence that NST occurs principally in BAT. It thus becomes reasonable to propose as a general principle that BAT is the primary anatomical site of the NST that is characteristic of many small mammals: CA adults, newborns, and hibernators alike.

Effect of acclimation temperature on the concentration of the mitochondrial ‘uncoupling’ protein measured by radioimmunoassay in mouse brown adipose tissue

“…The large changes with temperature reported here are, however, consistent with the very substantial alteration in the thermogenic activity of brown adipose tissue which occurs between warm and cold environmental conditions [2,3].…”

Effect of Diet and Cold Exposure on Norepinephrine Turnover in Brown Adipose Tissue of the Rat

“…If one assumes that endogenous NE levels (and thereby the density of sympathetic innervation) in BAT from other sites is similar to that in IBAT, then total BAT would contain four times as much NE as heart, or -2 ,ug of NE in animals of the size studied here. Because this NE is stored within the immediate vicinity of cells exhibiting thermogenic responses to NE, the potential of BAT for sympathetically mediated heat production is fully consonant with measurements of oxygen consumption in this tissue in vivo during NE infusions2 (3,9). The concordance of changes in NE turnover in IBAT with the known effects of dietary manipulation and cold exposure on oxygen consumption in the rat further supports a prominent role for the sympathetic nervous 2 Heterogeneous responses to infused NE have recently been noted among deposits of BAT at different sites (9); whether such variability occurs during cold exposure or with overfeeding is unknown.…”

“…Because ganglionic blockade exerted a greater effect on NE turnover in IBAT in cafeteriafed rats than in controls, the increase in NE turnover in IBAT with this overfeeding regimen reflects enhanced central sympathetic outflow. Thus NE turnover techniques can be satisfactorily applied to the INTRODUCTION Brown adipose tissue (BAT)' is now recognized as a major site of metabolic heat generation (nonshivering thermogenesis) in cold-acclimated rats, despite the fact that it represents only 1-2% of body weight in these animals (1)(2)(3). This highly specialized organ is located in interscapular, axillary, and paraspinal regions and within the thoracic and abdominal cavities and is capable of markedly increasing heat production over short time intervals.…”

Regulation of GDP binding and uncoupling-protein concentration in brown-adipose-tissue mitochondria. The effects of cold-acclimation, warm-reacclimation and noradrenaline

“…Functional brown adipose tissue (BAT) mitochondria are able to adapt their thermogenic capacity in response to both environmental temperature (Foster & Frydman, 1978) and dietary signals (Rothwell & Stock, 1983). Increased heat production is achieved by allowing proton re-entry into the mitochondrial matrix, via an alternative pathway to that associated with ATP synthesis.…”