ENDOCRINE GLANDS AND HYPOTHALAMIC OBESITY
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March 19661 NUTRITION REVIEWS 93
amount of protein ingested does not exceed a certain threshold. Since in both operated and intact animals food intake was de- creased by the higher protein levels, i t is suggested that the ventromedial nuclei are not functioning in this regulatory mecha- nism. Again the hyperphagic rats (average body weight 430 g.) greatly over-responded at the highest protein levels in comparison with the intact controls (average body weight 200 g.) if body mass is considered, since the two groups had a similar average daily intake.
In the second experiment i t was shown that the rats prefed with high protein diets easily adapted to the high leucine diet. The Pl0 and Pe0 diets were most effective in causing this facilitating effect of protein. All groups adapted to the La diet after re- ceiving it five to six days. The rats prefed the L6 diet, in which the added amino acids served to balance the excess leucine, did not adapt as quickly to the L, diet as did those rats prefed the high leucine diet alone.
The decrease of high protein diets and amino acid imbalanced diets may be due to 9 limitation imposed by the animals ability
to metabolize large quantities of dietary nitrogen within a short period of time. It is known, though, that prefeeding diets high in protein causes increased activity of he- patic enzymes associated with amino acid nitrogen metabolism. This adaptation should diminish the influence on food intake of a diet such as L5 , as indeed Krauss and Mayers second experiment demonstrates.
The authors concluded that a safety valve effect on protein and amino acid intake is independent of the activity of the ventro- medial satiety centers. This conclusion is subject to one qualification: that the hypo- thalamic hyperphagic rats employed had a wide gradient of weights, which probably indicates a variance in amount of ventro- medial nuclei destruction. It seemed that the animals a t the higher body weights were better able to maintain a high protein intake over a wider range of dietary protein levels, while the least heavy rats may not have been able to tolerate the most extreme diets. This effect may be a result of the very low levels of carbohydrate in the high protein diet.
ENDOCRINE GLANDS AND HYPOTHALAMIC OBESITY
Pancreatic beta and adrenal cortex fascicular zone cells had increased nuclear volumes in rats made obese b y hypothalamic lesions.
Various factors have been considered 8s primary or secondary causes of the obesity observed following hypothalamic ventro- niedial lesions. It is not clear from the liter- ature what are the effects of many of the endocrine changes accompanying this type of obesity. Especially inconsistent have been the changes observed in pancreatic beta cells (F. X. Hausberger, Fed. Proc. 17, 67 (1958); W. Gepts, Ann. Endocrinol. 24, 140 (1963) ; Hausberger, G. L. Broadhead, Jr., and B. C. Hausberger, Acta Endocrinol. 45,600 (1964) ) .
G. Sdtb16 (Acta Physiol. Acad. Sci. Hung.
27, 376 (1966)) has conducted an experi- ment designed to collect data on changes of the endocrine glands in general, and espe- cially of the pancreatic islets of rats with hypothalamic obesity. The author was par- ticularly interested in whether an altered function of these organs might play a role in causing hypothalamic obesity.
Electrolytic lesions in the hypothalamic ventromedial nuclei were caused in a group of 60 to 70 g. male rats. Thirteen were de- fined as obese; these rats and eight control rats were studied for one year. Eleven months after the lesions were caused, blood
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glucose was determined in the fasted state after 400 mg. of glucose per 100 g. body weight were injected intragastrically. One year after the lesions were caused, the ani- mals were sacrificed; the following parame- ters were measured: I131/s-ratio, body weight, nose to anus length, tibia1 length, and pituitary, thyroid, adrenals, and testes weights.
Histological studies were done on the pituitaries, pancreas, testes, thyroid, brains, and adrenals. Nuclear volume of the pan- creatic beta cells and of cells in the fascicu- lar zone of the adrenals was determined. Spermiogenesis was quantitatively studied.
Rats with lesions of the hypothalamus weighed more than controls a t the end of the experiment: 417 g. versus 345 g. (P < 0.01). The obese rats had slightly shorter bodies and tibiae. The mean absolute weight of the adrenals of the obese rats was greater than the controls: 68.5 mg. versus 47.5 mg. The hypophyses of the obese rats weighed less than those of the controls (8.6 mg. versus 12.1 mg.) ; the obese rats hypophyses and testes both weighed less per unit of body weight than those of the controls.
Ventromedial nuclear lesions were histo- logically demonstrated in the obese animals. The nuclear volume of the fascicular zone cells was greater in all obese animals than in the control rats: 120 versus 70p3 ( P < 0.01). The other two adrenal cortex zones and medulla were also hypertrophied. Obese rats had reduced lipids or none in the fascicular zone. The other adrenal cortex areas had either normal or increased lipid contents. The mean nuclear volume of pan- creatic beta cells in obese rats was greater than that in the controls (90 versus 65p3) . The amounts of aldehyde-fuchsin positive granules in the beta cells were similar in both groups. All phases of spermiogenesis were detected in about the same percentage in both groups.
Fasting blood glucose levels of the two groups were similar, but intragastric injec-
tion of glucose caused a greater rate of in- crease, and higher and more sustained blood glucose levels in the obese animals.
Both groups demonstrated an abnormally high T/s ratio. The obese rats had the lesser mean ratio of 60 while the control animals had a mean ratio of 119. The high ratioq were thought to be due to the low iodine content of the food.
Hyperadrenocorticism causes obesity and hypertrophy and hyperplasia of the beta cells of the pancreas (Hausberger and Hausberger, Am. J . Clin. Nutrition 8, 671 (1960)). Obesity does not occur in mildly alloxan-diabetic rats when corticosteroids are administered, even though normal ratp do become obese, thereby suggesting that circulating corticosteroids do not alone pro- duce obesity. Adrenalectomy was not found to prevent obesity caused by hypothalamic ventromedial lesions. SktA16s experiment in- dicates that obese rats with ventromedial lesions also show hypertrophy of the fascic- ular zone and the pancreatic beta cellular nuclei, thereby indicating accelerated re- lease of corticosteroids and insulin. This may contradict other results in which hypo- thalamically caused obesity in rats did not appear to be associated with pancreatic beta cell hypertrophy (F. X. Hausberger, Fed. Proc. 17, 67 (1958)). Even though Haus- berger and Hausbergers work (Zoc. cit.) indicates that adrenal hyperactivity would not be essential for the hypothalamic obe- sity SktA16 was studying, i t did occur. Fur- thermore, since adrenal hyperactivity did occur, one would predict, from Hausberger and Hausbergers work, that pancreatic beta cell hyperactivity would also occur because of the excess of circulating corti- costeroids. These two phenomena, appearing concurrently, do cause obesity (Hausbergei and Hausberger, Am. J . Physiol. 193, 455 ( 1 958) ) .
Another factor that could account for the pancreatic beta cell nuclei hypertrophy is increased hypothalamic lateral area actio-
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ity. This would be caused by the ventro- met l id nuclei lesions, since the nuclei nor- mally inhibit lateral area activity to varying degrees, It has been shown that electrical stimulation of a dogs hypotha- laiiiic lateral area, i e . , increased lateral area activity, causes an immediate increase of tlic insulin content of pancreatic venous blood (T. Kuzuya, J . Jap . SOC. Int. Med. 51, 1048 (1962)) .
It is not a t all clear what caused the hy- pertrophy of the adrenal or pancreatic areas. Sit616 suggests that adrenal hyperfunction in obese animals with hypothalamic lesions
should be considered as a secondary phe- nomenon caused by the obesity acting as a stressor. The hyperphagia elicited hypo- thalamically could possibly be a conse- quence of horinonal factors changed by the lesions.
Animals in which lesions of the ventro- medial nuclei of the hypothalamus were produced and which became obese also ex- hibited hypertrophy of the nuclear cells of the fascicular zone of the adrenal cortex and pancreatic beta cells. It is not clear what interrelationships existed or what caused the cellular changes.
NOTES Physical Activity and Serum Cholesterol
The possibility that increased physical activity might reduce development of coro- nary atherosclerosis has received considera- hle attention in the past few years (Nut~i - (ion Reviews 21, 178 (1963)) since higher wiin cholesterol levels and cardiovascular iiiortality rates have been observed in men aho were less active physically. A compari- son of several types of physical activity n.ith respect to serum cholesterol has been made by D. E. Campbell ( J . Lipid Res. 6, 418 (1965) ) . Previous work indicated that activity involving running lowered serum cholesterol, but more static exercise did not.
The subjects were male freshman college ;tudents who were selected a t random from hose enrolled in different physical educa- tion classes for a ten week period. These classes included cross-country running, might lifting, tennis, golf, tumbling-gym- nastics, and wrestling. A control group in- cluded students who were not enrolled in physical education classes.
Serum cholesterol was determined on insting blood samples taken on three suc- cessive mornings before the start of the activity period and on three successive
mornings before the end of the activity pe- riod.
The group enrolled in cross-country run- ning showed the largest decrease in serum cholesterol after ten weeks. This decrease was significant in comparison with the con- trols, who showed a slight increase in com- parison with all the other groups, except that playing tennis. This group also showed a significant decrease in serum cholesterol, in comparison with the controls and with the groups on wrestling, weight lifting, and gymnastic routines. Students in the latter three classes showed no significant change in serum cholesterol after ten weeks. Golf produced a slight decrease.
The author tentatively concluded that physical activity of a dynamic type such as running could result in a decreased serum cholesterol level, but that a more static type of activity, although vigorous, did not result in a decrease.
It is unfortunate that no data were sup- plied on body weights of the subjects dur- ing the study. Possibly the changes in serum cholesterol were related to body weight changes. H. J. RIontoye et nl. (Am. J . Clin. iVzh-ition 7, 139 (1959) ) concluded that reduction in serum cholesterol in subjects