No abstract

Estradiol benzoate (EB) treatment of male and female C57BL/6J oblob mice for 32 days led to decreased body weight (20%), percentage body fat (8%) and carcass protein content (12%) when compared with non-EB-treated obese control mice. Estradiol reduced the caloric intakes of both genders by 25-35% but did not affect body temperature regulation. Circulating glucose and insulin concentrations were also lowered by estrogens, although hyperinsulinemia persisted. Since post-treatment body weight changes correlated with daily food intakes (r = 0.8 1 ) rather than to rectal temperatures (r = -0.19), it appears that hypophagia provided a greater contribution to the estrogen-mediated reductions of growth and carcass fat than did altered energy expenditure for thermoregulation. While these data show that EB treatment does reduce the severity of some metabolic disturbances in a genetic model of type I1 diabetes, long-term estrogens do not appear to offer substantial advantages in the treatment of obesity or diabetes when compared with the effects of caloric restriction alone.

The body temperatures of mature lean and obese C57BL/6J mice were measured just after feeding, during ad libitum access to food, or every 24 h throughout a 3-day fast. Obese mice had body temperatures 1.0–1.4 °C lower than lean mice in the postprandial state and during ad libitum feeding. During food deprivation, obese mice became more hypothermic than lean sex-matched controls. A 5 °C fall in body temperature was observed in mutant females in the first 24 h of starvation, about twice that seen in any other experimental group. Over the same period the temperature changes of obese males and lean females were similar and both groups had larger hypothermic responses than lean males. The present results indicate that both genotype and gender affect thermoregulation in these mice. Under normal colony room conditions (ad libitum feeding, 23 °C) the ob/ob mutation is expressed by lower body temperatures which along with hypoactivity and hyperphagia account for the high rates of energy storage. When food availability is limited, females of both phenotypes display an increased capacity to reduce their maintenance energy requirements by lowering body temperatures. This hypothermia may be responsible for both the increased conservation of body mass seen during starvation and the slightly greater (5 %) fat stores observed in female mice.

In ob/ob mice a 12-wk period of food restriction led to a reduced rate of somatic growth and a decreased lean body mass, along with small but reliable reductions in systemic immunoreactive insulin levels and evidence of increased insulin sensitivity. However, no effects of limited access to food were noted on the basal hyperglycemia, the elevated percent carcass lipid, or on the significantly higher levels of serum corticoids that occur in obese animals. These data indicate that hyperphagia alone is not responsible for the maintenance of many of the commonly reported characteristics of the obese-hyperglycemic syndrome, but do not exclude the contribution of factors secondary to the quantity of ingested food. Additionally, the present data lend support to recent work suggesting that chronic hyperinsulinemia or an elevated set point of total carcass lipid may be instrumental in the development of this syndrome.

The American obese mouse (ob/ob) is characterized by an elevated level of blood glucose over much of its adult life. The presence in the mature ob/ob mouse of 1) adrenal cortical hypertrophy (Hellerstrom, HeIlman and Larsson 1962), 2) increased glucocorticoid production in vitro (Carstensen, Hel/man and Larsson 1961), and 3) a reduction of blood glucose following bilateral adrenalectomy (Solomon and Mayer 1973) has led to the suggestion that elevated glucocorticoids are responsible for the hyperglycemia of the ob/ob mouse. Additionally, the implantation of ACTH secreting tumors to thc non-obese mouse produces many characteristics of the obese-hyperglycemic syndrome including fasting hyperglycemia (Shul/, Cahill Jr., Gadsden and Mayer 1956), augmented lipogenesis (Zomzely and Mayer 1956), and obesity, pancreatic beta-cell hyperplasia, and hyperphagia (Hausberger and Ramsay 1959). Ta further explore the participation of glucocorticoids in the hyperglycemia of the obese mouse the fasting levels of serum glucose, immunoreactive insulin and immunoreactive corticosterone were measured in mature lean and obese mice.