Cold acclimation (4 degrees C) and "cafeteria diets" increased the thermic response of rats to catecholamines. This phenomenon was accompanied by six- to eightfold increases of interscapular brown adipose tissue (IBAT) weight, total tissue cytochrome oxidase activity, and total number of brown adipocytes. Quantitative radioautographic experiments using [3H]thymidine disclosed that cold exposure markedly enhanced the mitotic activity in blood capillaries and small-venule endothelial cells, adipose tissue interstitial cells, and preadipocytes rather than in fully differentiated brown adipocytes. IBAT mitotic index increased 70 times over control values after only 2 days of cold exposure. Thereafter, the proliferative activity progressively decreased. IBAT cell composition was modified during cold acclimation as the percentage of interstitial cells and preadipocytes increased over the other cellular types. Because brown adipose tissue is the principal site of norepinephrine-induced thermogenesis in homeothermal animals, it is suggested that brown adipocyte proliferation from precursor cells represents the fundamental phenomenon explaining the increased capacity of cold-acclimated animals to respond calorigenically to catecholamines.

The effects of exercise training and food restriction on the regulation of lipolysis were studied comparatively in adipocytes isolated from male and female rats. Exercise training inhibited cell proliferation in parametrial, but not in epididymal adipose tissue, whereas it significantly reduced adipocyte size in both fat depots. Adipocyte capacity for responding lipolytically to epinephrine (10 microns) or to ACTH (1 micron) was markedly increased by exercise training. Enhanced lipolysis was also observed when cells isolated from exercise-trained animals were stimulated by bypassing with dibutyryl cyclic AMP (5 mM) or theophylline (5 mM) the early metabolic steps associated with hormonal activation of the adenylate cyclase complex. Significantly, binding of (-)-[3H]dihydroalprenolol to cellular receptor sites was not affected by exercise training. It is therefore concluded that exercise training increases adipocyte responsiveness to lipolytic hormones at a metabolic step distal to stimulus recognition by adrenoreceptors, possibly at the level of protein kinases or lipases. Food restriction markedly reduced adipocyte size and partially mimicked the effects of exercise training on adipocyte proliferation and lipolysis.

Regulation of respiration by catecholamines was studied in adipocytes isolated from interscapular brown adipose tissue of warm-acclimated rats by rapid digestion of collagenase. (-)-Norepinephrine stimulated adipocyte respiration 10–12 times above basal values in less than 3 min. (Vmax = 410 +/- 29.5 nmol O2 . min-1 . 10(-6) cells-1). Stimulated respiration remained stable for at least 20 min, provided that cells were incubated in balanced salt media containing bicarbonate. The maximal capacity of total brown adipose tissue for norepinephrine-stimulated respitarion was estimated at 1.5 ml O2/min per rat. beta-Adrenergic agonists increased calorigenesis stereospecifically with an order of potency expected for respiratory stimulation via adrenoceptors of the beta 1-subtype: (-)-isoproterenol (1/2 Vmax = 2 nM) greater than (-)-norepinephrine (1/2 Vmax = 20 nM) approximately equal to (-)-epinephrine (1/2 Vmax = 40 nM) greater than corresponding (+)-stereoisomers. The alpha-adrenergic agonist phenylephrine (1/2 Vmax = 5 microM) stimulated adipocyte respiration as rapidly and as effectively as beta-agonists. Although alpha-adrenoreceptors are present in brown adipose tissue, studies with alpha- and beta-adrenergic antagonists revealed that norepinephrine elicits thermogenesis at physiological concentrations (less than or equal to 1 microM) predominantely via beta 1-adrenergic pathways.

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Rats consuming Coca-Cola and Purina chow ad libitum increased their total energy intake by 50% without excess weight gain. Their resistance to cold was markedly improved. These phenomena were characterized by significant increases in interscapular brown adipose tissue weight (IBAT) (91%), cellularity (59%), triglyceride content (52%), protein content (94%), and cytochrome oxidase activity (167%). In contrast, Coca-Cola consumption did not significantly affect the cellularity or triglyceride content of parametrial white adipose tissue (PWAT), although it slightly augmented PWAT weight. The effects of Coca-Cola on cold resistance, IBAT cellularity, and composition were entirely reproduced by sucrose, but not caffeine, consumption. Although caffeine also increased IBAT cellularity and composition, it significantly decreased the rate of body weight gain, PWAT weight, and adipocyte size. Moreover, it markedly inhibited adipocyte proliferation in PWAT thereby mimicking the effects of exercise training and food restriction (Bukowiecki et al., Am. J. Physiol. 239 (Endocrinol. Metab. 2): E422-E429, 1980). It is concluded a) that sucrose and Coca-Cola consumption improve the resistance of rats to cold, most probably by increasing brown adipose tissue cellularity, and b) that moderate caffeine intake might be useful for inhibiting proliferative activity in white adipose tissue, thereby preventing obesity.