1. The onset of cold-induced thermogenesis was studied in a strain of mice which produced among their offspring genetically-obese (ob/ob) individuals. A thermogenic response was present in a majority by day 5 after birth.2. The thermogenic response to cold was measured on days 5, 10 or 15 after birth, and the animals reared and the onset of obesity noted. The correlation between the subsequent development of obesity and a poor thermogenic response in early life was low.3. A poor thermogenic response at day 15 was associated with the presence in brown adipocytes of mitochondria with disordered internal structures.4. At day 42 both non-obese and obviously-obese mice showed a similar thermogenic response to moderate cold exposure.5. It would seem that in this strain of mice disordered internal mitochondria1 structure in brown adipose tissue is associated with a poor thermogenic response to cold, but not invariably with the subsequent onset of obesity.

Thermoregulatory responses to pyrogens in the immediate newborn period have been reported suppressed or undeveloped. In this study we investigated these responses in the newborn rabbit. Endotoxin (Escherichia coli LPS) was injected intraperitoneally in rabbits at different doses on day 0 (day of delivery), 1 or 3 of life, each animal being used only once. Oxygen consumption (VO₂) and colonic temperature (Tc) were measured continuously for up to 5 h following endotoxin administration. On all days, a thermogenic response of a similar pattern was seen. At a low dose of endotoxin, there was a monophasic rise in VO₂ that reached a peak at 2 h, followed by a plateau phase lasting a further 2-3 h. At an intermediate dose the response was biphasic with an initial smaller peak after 45-60 min and a second more sustained peak developing by about 2 h. At a higher dose the depression between the two peaks became deeper and longer with the second peak becoming more delayed and weaker. As animals got older, the doses needed to produce this sequence increased. On day 0 the increased VO₂ caused by endotoxin was not accompanied by an increase in Tc. By day 3, Tc rose with the increase in VO₂. We conclude that rabbits on the day of delivery respond to endotoxin with an increase in VO₂ and by day 3 this is accompanied by an increase in Tc. The pattern of VO₂, changes from monophasic to biphasic with increasing doses of endotoxin and the sensitivity to endotoxin decreases over the first 3 days of life.

The preferred environmental temperature (T_E) and rates of oxygen consumption (VO₂) around the thermal neutral range were measured in rabbits on the day of birth and 2, 7 and 14 days after birth. On day 0, the preferred TE was 38.0 ± 0.8 °C, and it fell to 30.4 ± 0.5 °C by day 14. Day-0 rabbits kept for 1 h in a warm (41 °C), neutral (39 °C) or cool (28 °C) environment selected a different TE at 39.8, 39.5 and 37.3 °C, giving colonic temperatures (T_c) of 40.8, 39.9 and 37.7 °C, respectively. A similar phenomenon occurred on day 2, but not on day 7. It was concluded that newborn rabbits select a TE to match that which they experienced in utero and that this preferred TE changes after birth depending on the temperature of their surroundings and the development of their thermoregulatory control.

The onset of thermogenesis in response to cold exposure in individual mice was studied using a sensitive close circuit system for measuring their rate of oxygen consumption. On the day of birth, exposure to a cool environment did not stimulate an increase in oxygen consumption, but 48 h later the majority of mice respond by doubling their metabolic rate in response to a fall from 36 to 31 °C in ambient temperature. When 5 mice huddled together an ambient temperature drop from 36 to 23 °C was required to provoke the same response. Brown adipose tissue is present at birth but the cells are relatively small and contain little fat. By the second day they are three times larger and contain far more fat. The onset of thermogenesis appears to await the development of brown adipose tissue.

SUMMARY1. Metabolic responses of endotoxin-injected newborn rabbits were measured in a closed circuit calorimeter at a constant environmental temperature within their thermoneutral range. Oxygen consumption and colonic temperatures were then measured over a range of environmental temperatures from 21-0 to 40 0°C and the responses of endotoxin-injected rabbits compared with non-injected litter mates.2. To measure their preferred thermal environment, endotoxin-injected and noninjected litter mates were allowed to settle on a thermal gradient and their colonic temperatures measured.3. In a constant environmental temperature of 37°C, rises in oxygen consumption and colonic temperature following endotoxin injection were found to be biphasic.Oxygen consumption rose from 21 ml kg-' min-1 to a maximum 35 ml kg-1 minand colonic temperature rose from 39 0 to 39 8 'C.4. The maximal rate of oxygen consumption was the same in both injected and non-injected animals, 53 ml kg-1 min-', being provoked at the same environmental temperature of 24 'C. Minimal rates of oxygen consumption were also similar for the two groups but in the injected animals they were achieved at an environmental temperature of 39°C, 2 'C higher than for non-injected animals.5. We conclude that newborn rabbits challenged with a pyrogen have both behavioural and physiological responses. The thermogenic response is consistent with a change in sensitivity to feedback information rather than a simple shift in the central thermoregulatory set point. We find no evidence to support the view that in the febrile response a higher body temperature necessitates an increase in metabolic rate, the so-called Q1o effect.