DISCUSSION ON EXPERIMENTAL APPROACHES TO OBESITY Dr. GC Kennedy: Experimental Hypothalamic Obesity. Physicians have recognized fora long time that obesity is associated in some way with the hypothalamic-pituitary complex. Frohlich (1901) traced descriptions of gross obesity with tumours of this region in the clinical literature as early as 1840. Both he andBabinski (1900) related the obesity to diminished secretion of the pituitary. But Erdheim, in 1904, held that it was due to damage to the hypothalamus, and subsequent clinical work has done littleto settle the controversy. Unfortunately, pathological processes are seldom so localized that they can be said with confidence to be entirely glandular or entirelynervous. However, in the last ten years experimental studies of hypothalamic obesityin animals have done something to simplify the position.

Ever since 1913, when Camus and Roussy showed that hypophysectomy in the dog never caused an increase in weight unless the base of the brainwas damaged at the same time, there have been attempts to produce pure hypothalamic obesity experimentally. But it was not until 1939 that SW Ranson (Hetherington and Ranson, 1939) was able to do it regularly by making small electrolytic lesions in the brain with an electrode introduced from above, leaving the pituitary intact. Brobeck, et al.(1943) improved the technique, used much smaller lesions, got much more striking obesity, and showed that bilateral damage to the nuclei of the tuber cinereum was the essential lesion. In 1943, Hetherington, one of Ranson's colleagues, showedthat hypophysectomy either before or after the hypothalamic operation failedto prevent the obesity, and concluded that the pituitary played no part in its production. The original work was done on the rat, but it has been confirmed in thecat, the dog and the monkey. Although, clinically, cases ofobesity where one can demonstrate organic damage to the hypothalamus are rare, I think one can learn something from the behaviour of these rats which may help towards an under-standing of obesity in general. I shall restrict this description to some of the points which suggest analogies with human obesity. The animals I shall describe have beenprepared by Brobeck's technique. The obesity causes an enormous increase in weight, and a gross change in appearance compared with an unoperated controlrat, but there is no effect on skeletal length, although most of the operations were carried out during a period of activegrowth. This in itself is strong evidence of the absence of any pituitary damage. The fat is distributed fairly uniformly through all the usual depots. By comparison the parenchymatous organs are spared-for example, inrats which have yielded over 50% of fat from the body as a whole the liver fat has been less than 10%.