INVOLVEMENT OF EPIDERMAL GROWTH-FACTOR IN INDUCING ADIPOSITY OF AGED FEMALE MICE

Aged mice exhibit an increase in their body weight (BW), which is associated with fat deposit increase. Epidermal growth. factor (EGF) concentration in the submandibular gland also increases with aging. We examined the effects of elevated EGF on the adiposity of aged female mice. Studies were started in two groups of animals consisting of sham-operated (n=10) and sialoadenectomized (n=10, Sr; surgical removal of the submandibular glands) mice at 8 weeks of age. Body weight gain and food intake were measured throughout 78 weeks of age in these two groups. Body weight was significantly less in the Sr group throughout 78 weeks, while food intake was not changed by Sr after 12 weeks of age. To examine further if EGF plays a role in the induction of adiposity in aged female mice, sham-operated animals were given 100 mu l anti-EGF rabbit antiserum (anti-EGF group, n=5) or normal rabbit serum (control group, n=5) every 3 days, and Sr animals were given 5 mu g/day EGF (Sx+EGF group, n=5) or saline (Sx group, n=5) from 78 weeks of age for 3 weeks. At 81 weeks of age, all animals of these four groups were killed, and carcass fat deposition and fat cell sizes were measured. Although the relative weights (weight ratio to BW) of the Liver and kidney were not changed by Sr and anti-EGF treatment, the relative weights of mesenteric and subcutaneous fat tissues and adipocyte weights were significantly decreased in Sr and anti-EGF; groups compared with the control group. Moreover, both acyl-CoA synthetase (ACS) and lipoprotein lipase (LPL) mRNA levels were significantly decreased by Sr or anti-EGF administration in mesenteric and subcutaneous fat tissues. On the other hand, EGF administration to Sr animals had no effect on BW, fat tissues and adipocyte weights, and ACS and LPL mRNA levels. The results, however, were consistent with the fact that adipose tissue EGF receptors were down regulated in Sr mice. These findings suggest that EGF may play a role in the induction of adiposity in aged female mice.