Margaret Ashwell

Brown adipose tissue in the parametrial fat pad of the mouse.

Cold acclimation has been shown to produce a substantial increase in the number of brown adipocytes in the parametrial fat pad of female BALB/c mice ‐ a site normally thought to consist of typical white adipocytes. The brown adipocytes have been identified not only on the basis of their morphology using light and electron microscopy, but also on the basis of the content of the mitochondrial ‘uncoupling protein’ (M r = 32 000) which is characteristic of the proton conductance pathway of brown adipose tissue.

Measurement of rat brown-adipose-tissue mitochondrial uncoupling protein by radioimmunoassay: increased concentration after cold acclimation.

A specific antiserum has been raised against the 32 000-mol.wt. uncoupling protein from the mitochondria of rat brown adipose tissue and a sensitive radioimmunoassay for the protein has been developed. The uncoupling protein is present in large amounts in brown adipose tissue; its concentration is increased substantially by cold acclimation. The protein has not been detected in the liver, heart, or parametrial white adipose tissue of rats.

Control of white and brown adipose tissues by the autonomic nervous system

Interest in the neural regulation of the adipose tissues has increased considerably in recent years. In the case of brown adipose tissue (BAT) this reflects the development of the concept that the tissue is important in the regulation of energy balance. The substantial innervation of BAT has been recognized, however, for some considerable time (see Barnard et al. 1980). In the present paper we have set out to briefly summarize current views on the role of the autonomic nervous system, in practice the sympathetic system, in the control of both white adipose tissue (WAT) and BAT. The regulatory effects of the sympathetic system on these two tissues can be considered in terms of acute effects on the central metabolic pathways, and chronic effects relating to the growth and development of the tissues. The main emphasis of this review is on BAT, reflecting the more restricted picture of the role of the sympathetic system in the regulation of WAT.

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

The effect of acclimation temperature on the concentration of the mitochondrial ‘uncoupling’ protein (M r 32 000) from brown adipose tissue of mice has been investigated. The uncoupling protein was measured by a specific radioimmunoassay. Between 33°C (thermoneutrality) and −2°C there was a progressive increase with decreasing environmental temperature in the amount of uncoupling protein. For mice at −2°C the mitochondrial concentration of the protein was 9‐times higher than at 33°C, while the total amount of the protein in interscapulaar brown adipose tissue was estimated to be nearly 80‐times greater at −2°C compared to 33°C.

Measurement by radioimmunoassay of the mitochondrial uncoupling protein from brown adipose tissue of obese (ob/ob) mice and Zucker (fa/fa) rats at different ages

The concentration of the ‘uncoupling protein’ in brown adipose tissue mitochondria has been measured in lean and obese (ob/ob) mice and Zucker (fa/fa) rats at different ages using a specific radioimmunoassay. During the suckling period the concentration of the protein was similar in normal and mutant animals of both types, despite the decrease in mitochondrial GDP binding observed in the obese. The concentration of uncoupling protein was, however, decreased in adult ob/ob mice and adult Zucker rats compared with their respective lean siblings, in parallel with the decrease in GDP binding. It is concluded that there is a ‘masked’, or inactive, form of uncoupling protein in young ob/ob mice and fa/fa rats.

Adaptive changes in the concentration of the mitochondrial ‘uncoupling’ protein in brown adipose tissue of hamsters acclimated at different temperatures

The effect of acclimation at different temperatures on the activity of interscapular brown adipose tissue has been investigated in the hamster, a hibernator. Between 31° and 4°C the cytochrome oxidase activity of the tissue increased 4- to 5-fold, mitochondrial GDP binding per mg of mitochondrial protein doubled, and the amount of uncoupling protein rose from 1.7% to 5.4% of total mitochondrial protein. It is concluded that there are clear adaptive changes induced by temperature in brown adipose tissue of the hamster, but the changes are limited in comparison with those in the mouse.

Decreased Brown Adipose Tissue Thermogenic Activity Following a Reduction in Brain Serotonin by Intraventricular p-Chlorophenylalanine

The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fedad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake.