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The effect of cold exposure (0 degrees C, 1 h) on free fatty acid (FFA) mobilization and plasma glucose was studied in freely moving male rats injected with adrenergic blockers (phentolamine or propranolol) into the medial preoptic area (MPOA). The rats were implanted with chronic jugular catheters for blood sampling and with unilateral intracerebral cannulas placed just above the MPOA. Blood samples were taken 2 min before and 10, 20, 40 and 60 min after cold exposure. After cold exposure plasma glucose and plasma FFA levels rose rapidly, reaching a peak at 20 min post-stimulus. Previous administration of phentolamine (50 nmol), but not propranolol (100 nmol), into the MPOA blocked the glycemic response to cold exposure. On the other hand, previous administration of propranolol, but not phentolamine, into the MPOA blocked the increased FFA mobilization in response to cold exposure. On the basis of these results, we propose that MPOA alpha-adrenergic synapses relay impulses activating the sympathetic outflow expressed by neurally mediated hyperglycemia, and beta-adrenergic synapses relay impulses activating the sympathetic outflow to the adipose tissue, increasing FFA acid mobilization.

The effect of noradrenaline (NA) injection (20 or 40 nmol) into the preoptic area (POA) on plasma glucose and insulin was studied in male and female rats. The rats were implanted with chronic jugular catheters for blood sampling and unilateral intracerebral cannulas placed just above the POA. Blood samples were taken before and at 5, 10, 15, 30 and 60 min after NA injection. As early as 5 min after NA injection, plasma glucose levels rose rapidly in both male and female rats, reaching a peak at 15 min poststimulus. NA injection into the POA caused a dose-dependent hyperglycemic response in both male and female rats, although the response was more intense and longer lasting in females than in males. However, NA injection into the POA induced an increase in plasma insulin concentration in male but not in female rats. In addition, the increase in plasma glucose induced by 40 nmol NA injection in males preceded that of insulin. Plasma levels of glucose after POA injection of NA were already significantly elevated (p < 0.01) within the first experimental interval (5 min), whereas a plasma insulin increase were first detected 15 min post injection. We conclude that, when administered locally into the POA, NA can activate the sympathetic outflow expressed by a neurally mediated hyperglycemia which is more intense in females than in males. These data demonstrate that the POA has a sexually differentiated function in the regulation of glycemia.

The effect of norepinephrine (NE) injection into the medial preoptic area (MPOA) on plasma glucose was studied in freely moving male rats. The rats were implanted with chronic jugular catheters for blood sampling and with unilateral intracerebral cannulas placed just above the MPOA. Blood samples were taken immediately before and 5, 10, 15, and 30 min after NE injection. As early as 5 min after NE injection, plasma glucose levels rose rapidly, reaching a peak at 15 min poststimulus. The hyperglycemic response to NE injection into the MPOA was dose-related within the range of doses tested (10, 20, and 40 nmol). Previous administration of phentolamine (50 nmol), but not propranolol (100 nmol), into the MPOA blocked the hyperglycemic response to NE injection into the MPOA. The increase of plasma glucose induced by NE into the MPOA and the blockade of the hyperglycemic response to NE by phentolamine suggest the involvement of an alpha-adrenergic mechanism in MPOA-mediated hyperglycemia. On the basis of these and previous results, we propose that MPOA alpha-adrenergic synapses relay impulses activating the sympathetic outflow expressed by neurally mediated hyperglycemia.

Metabolic adjustment was studied in male Wistar rats weighing 180-200 g with bilateral electrolytic lesions in the preoptic area which were acclimatized to a hot environment (34 degrees C, 30 rats) and to normal temperature (25 degrees C, 20 rats) for 60 days. Oxygen consumption at 34 degrees C and body weight were measured periodically. Preoptic-lesioned rats (PO rats) showed a reduction in metabolic rate (from 46.2 +/- 2 to 33 +/- 2 Cal/m2 per h, P less than 0.05) regardless of the temperatures to which they were adapted. Although the reduced metabolic rate of PO rats living at 25 degrees C or 34 degrees C could be an indicator of adaptation to heat, only the PO rats living at 25 degrees C showed a weight gain (101 +/- 13 g) similar to that observed for the sham-operated control (75 +/- 11 g). In fact, the PO rats living at 34 degrees C failed to increase their body weight during 60 days of exposure to heat. These data indicate that the preoptic area is essential to integrate the thermal input with the energy-linked metabolic process involved in adaptation to hot environments.

The cold-adaptation process was examined in preoptic-lesioned (PO, 18 rats) and adrenaldemedullated-preoptic-lesioned rats (ADPO, 16 rats). PO rats and ADPO female Wistar rats were cold acclimatized to 5 degrees C for 2 operated and then treated exactly like the lesioned rats. Lesions in the PO region caused a decrease in the ability to maintain normal body temperature in a cold environment (5 degrees C for 2 h). Their colonic temperature fell even by the end of the 2nd h of cold exposure (-1.1 degrees C for PO rats and -1.25 degrees C for ADPO rats, P less than 0.01). However, after 2 weeks of cold acclimation the PO rats, but not the ADPO rats were able to thermoregulate in the cold and showed a normal increase in interscapular brown adipose tissue weight (79%, P less than 0.01). These data suggest that the PO is not an essential link for cold adaptation when a mild cold-adaptation method is used. Furthermore, the data show that increased adrenal medullary activity is required for the cold adaptation process in PO rats.

Metabolic adjustment was studied in rats with bilateral electrolytic lesions in the preoptic area which were exposed to heat (34 degrees C) and to normal temperature (25 degrees C) for 60 days. The metabolic rate measured at neutral temperature (29 degrees C) in preoptic-lesioned rats living at 25 degrees or 34 degrees C was reduced to 80% the rate of sham-operated controls. The increase in metabolic rate induced by heat (30 min at 34 degrees or 37 degrees C) in preoptic-lesioned rats, living at 25 degrees C, was markedly reduced to 10% the rate of sham-operated controls living at 25 degrees C. In preoptic-lesioned rats, the increased metabolic rate induced by heat exposure (34 degrees or 37 degrees C) was impaired, regardless of the living ambient temperature (25 degrees or 34 degrees C) of the animal. These data demonstrate the participation of the preoptic area in heat-induced increased oxygen consumption and provide additional evidence for its role in the integration of thermal inputs with energy-linked metabolic processes.

Previous studies indicated that a longitudinal pathway connecting preoptic, lateral, and posterior hypothalamic areas participates in the process of free fatty acid (FFA) mobilization in the rat. In the present experiments, the presence of sensitive neurons in the preoptic area was investigated by examining the effects of topical stimulation with 2-deoxyglucose (2-DG) or insulin on the levels of plasma FFA in conscious unrestrained rats. Microinjections of minute amounts (50 micrograms and 1 microliter) of 2-DG into the preoptic area of fed animals induced rapid increases in the concentration of plasma FFA. Microinjections of insulin (5 microU and 0.5 microliter) produced sharp decreases of the elevated plasma FFA levels in fasted rats. Both 2-DG and insulin induced small increases in plasma glucose that did not differ from similar increases induced by equal volumes of 0.15 M NaCl. The results provide direct evidence for the presence within the preoptic area of insulin-sensitive glucoreceptors involved in FFA mobilization. The data suggest that activation of these receptors and increased sympathetic outflow to adipose tissue contributes to fasting lipolysis.

The increase in plasma free fatty acids (FFA) induced by cold (2 h at 5 degrees C) in rats with bilateral electrolytic lesions in the preoptic area was reduced to 30% compared to sham-operated controls. Blood glucose of lesioned rats increased 35% over initial levels and remained elevated, whereas in controls it returned to initial levels after 2 h. Rectal temperature decreased 3 degrees C in lesioned rats but not in controls. These data demonstrate the participation of the preoptic area in cold-induced FFA mobilization and provide evidence for the role of this area in the integration of thermal inputs with energy-linked metabolic processes.