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.

The metabolic interactions of cold exposure, cold acclimation, and starvation on glucose tolerance and plasma insulin levels were studied in precannulated, unrestrained, and unanesthetized rats. Cold exposure (48 h at 5 degrees C) significantly reduced the insulin response to intravenous glucose injection (P less than 0.01) while improving glucose tolerance (P less than 0.01). Starvation (48 h at 25 degrees C) also reduced the insulin response (P less than 0.01) but did not significantly alter glucose tolerance. "Accelerated starvation" induced by starving rats for 48 h at 5 degrees C dramatically reduced both basal and glucose-stimulated insulin levels while even improving glucose tolerance, resulting in a 15-fold reduction in the insulinogenic index. Cold acclimation (3 wk at 5 degrees C) induced essentially the same alterations as cold exposure. Approximately reversed changes were observed when cold-acclimated rats were returned to a warm environment for 15-18 h. Results from these studies indicate that 1) cold exposure and starvation, but not cold acclimation, act synergistically in decreasing the sensitivity and/or the capacity of pancreatic islets for secreting insulin in response to glucose stimulation; 2) glucose tolerance and possibly insulin sensitivity of peripheral tissues are enhanced by cold exposure and starvation, although glucose tolerance is improved by cold exposure only, not by starvation; 3) an improved glucose tolerance with barely detectable plasma insulin levels was obtained in cold-starved rats under normal physiological conditions.

Long-term cafeteria feeding, cold exposure, and the combination of treatments increased energy intake in female Wistar rats by 25%, 113%, and 150%, respectively, in comparison with controls (P less than 0.01). Although cafeteria feeding at room temperature markedly increased the insulin response to an intravenous glucose tolerance test (IVGTT), glucose tolerance was deteriorated (P less than 0.01). In contrast, cold exposure significantly improved glucose tolerance in the presence of a reduced insulin response in Purina- and cafeteria-fed animals. Moreover, cold exposure also decreased body weight gain and increased brown adipose tissue mass, total cytochrome-oxidase activity, and cellularity by approximately 600-800%. The results suggest that cold exposure enhances insulin sensitivity of peripheral tissues, whereas hyperphagia on a high-fat, low-protein diet leads to insulin resistance. In addition, the results demonstrate that prolonged stimulation of energy expenditure by cold exposure not only reverses the diabetogenic effects of cafeteria feeding but also improves glucose tolerance. This phenomenon could result from a combination of two factors: (1) a cold-induced prevention of obesity; and (2) an enhanced disposal of circulating glucose into peripheral tissues, including brown adipose tissue.

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.

The effect of a continuous infusion of norepinephrine (NE) on glucose disposal in vivo was examined in conscious restrained rats using the euglycemic-hyperinsulinemic clamp technique. NE, 1,000 micrograms.kg-1.day-1 (130 nmol.kg-1.h-1) or vehicle (CO) was infused for 10 days in adult male Sprague-Dawley rats using subcutaneously implanted osmotic minipumps. Body weight and food intake were similar in both groups of animals throughout the study. Fasting basal plasma glucose and insulin concentrations were similar in both groups. However, basal hepatic glucose production (HGP) was increased by NE treatment (9.03 +/- 0.63 vs. 13.20 +/- 1.15 mg.kg-1.min-1, P less than 0.05, CO vs. NE, respectively). Insulin infusions of 2, 6, and 200 mU.kg-1.min-1 suppressed HGP to the same degree in both groups. During 2, 6, and 200 mU.kg-1.h-1 insulin infusions the glucose disposal rate was 65, 60, and 13% greater in NE-treated animals than in controls. Acute beta-adrenergic blockade with propranolol infused at 405 nmol.kg-1.h-1 during the glucose clamps did not normalize glucose disposal. These results demonstrate that chronic NE infusion is associated with increased basal glucose turnover and increased insulin sensitivity of peripheral tissues.