Search

A model of dietary obesity was developed, in adult male rats, where duration of feeding of a high fat diet (HFD; 60 percent of calories as fat) influenced capacity to reverse the obese state following a reduction in dietary fat. After 17, and again after 30 weeks, groups of HFD fed rats were returned to ad libitum feeding of a low fat, chow diet (C; 14 percent fat). The rats switched from HFD to C after 17 weeks returned to control levels of body weight and body composition, but the rats switched from HFD to C after 30 weeks did not. This latter group remained heavier than controls without ingesting more energy, indicating an increased energy efficiency and a reduction in energy requirements. These results suggest that energy balance during development of dietary obesity may be different from energy balance in long-standing dietary obesity. In addition to demonstrating that duration (and/or severity) of dietary obesity is an important variable in the potential reversal of the obese state, the results provide further evidence that persistent obesity is not maintained solely by an elevated energy intake. A corollary to these findings is that treatment of dietary obesity may be more effective if begun early.

We studied changes in energy utilization in mature female rats exposed to varying degrees of food restriction. Food-restricted rats showed considerable energy conservation, exhibited primarily as a reduction in the energy required for daily maintenance. When a given body weight loss was produced by starvation (3 or 6 d), changes in body composition and energy utilization differed only slightly (and temporarily) compared with the same body weight lost by partial food restriction. All food-restricted groups demonstrated a remarkable ability to reduce maintenance energy costs and to achieve zero energy balance at food intakes 40-50% of controls. By contrasting these results with our previous work in food-restricted male rats, we identified possible gender differences in the response to food restriction. Females appear to preserve lean mass to a greater degree than male rats by utilizing relatively more fat for energy needs. This preference for fat as a fuel during negative energy balance suggests that females would lose less body weight for a given reduction in carcass energy than males, since fat is calorically denser than lean mass.

A prospective study of a new surgical approach (modified subtotal thyroidectomy) in the management of Graves' disease was carried out in 55 patients. The patients were followed over an average of 4 years with a strict protocol involving serial clinical and chemical evaluations (T4, T3RIA, TSH) and yearly thyroid scans. Long-term euthyroidism was achieved in 94% of the patients. These results are markedly superior to the functional results occurring after the standard thyroidectomy in widespread current use. In particular, the development of postoperative hypothyroidism, which is usually manifest by the second year after operation, has not occurred in this series. Observations of TSH elevations in som euthyroid postoperative patients may have important implications regarding the mechanism by which appropriate surgical resection favorably affects the pathophysiology of Graves' disease.

Growth hormone (GH) binding and the effect of GH and insulin on glucose metabolism in rat adipocytes were studied at various time periods following hypophysectomy. Male rats were hypophysectomized at 33-34 days of age. After 6 h, 20 h or 3, 7 and 14 days adipocytes were prepared from epididymal fat pads by mild collagenase digestion (0.5 mg X ml-1, 60 min, 37 degrees C). Glucose metabolism was studied by determining the production of CO2 from [14C]glucose and the incorporation of [14C]glucose into lipids. GH binding was measured in cell aliquots using [125I]hGH. No difference in GH binding to adipocytes was observed between control rats and rats hypophysectomized or sham-operated 6 h earlier. GH binding was significantly decreased 20 h after hypophysectomy and declined further with time after hypophysectomy. Adipose tissue from normal rats is usually refractory to the insulin-like effect of GH. Adipocytes isolated from normal rats were, however, usually responsive to GH immediately after cell isolation, suggesting that refractoriness to the insulin-like effect of GH was lost during the time required for the preparation of adipocytes. The magnitude of the response to GH in adipocytes progressively declined with time after hypophysectomy. The decreased responsiveness to GH with time after hypophysectomy parallelled the decrease in GH binding. The results suggest that the pituitary, directly or indirectly, is necessary for the maintenance of GH binding sites in adipose tissue and that these binding sites are related to the insulin-like effect of GH.

We describe a new method of studying the thermic response to dietary fuels that involves continuous infusion of a liquid formula diet through a thin nasogastric tube. The data show that the steady inflow of dietary fuel is accompanied by a relatively constant level of energy expenditure, the magnitude of which depends on the rate of fuel inflow. An increase in the rate of fuel infusion above that required for caloric maintenance leads to a rise in energy expenditure. We also give examples, based on preliminary observations, of how the technique can be used to more precisely quantify energy metabolism. The technique may prove useful in the studying efficiency of energy utilization and in examining the extent to which individuals differ in energy efficiency.

The relationship between size of a mixed, liquid meal and the thermic effect of food (TEF) was studied in two groups of nonobese male subjects differing in maximum aerobic capacity (VO2 max). A design using repeated measures was chosen in which each subject received each meal (water, 500 kcal, 1000 kcal, 1500 kcal) on a different morning. TEF was measured by indirect calorimetry for three hours following each meal and was found to increase systematically, in a nonlinear fashion, as meal size was increased. Subjects with a high VO2 max responded to the two higher calorie meals with a greater TEF than did subjects with a low VO2 max. They also showed a greater increase in TEF for any given increase in meal size. This study establishes a precise relationship between meal size and the thermic effect of food. It also identifies an important variable, VO2 max, in determination of the individual thermic response to food. These findings suggest that individuals with a high VO2 max (such as aerobically trained athletes) show a greater caloric expenditure after eating, particularly after a large meal, than do individuals with a low VO2 max. A high thermic response to food could be beneficial in body weight homeostasis.

Although it has been thought that future thyroid function after subtotal thyroidectomy for Graves' disease was intimately related to the mass of the thyroid remnant, long-term functional results have not been clearly established. These questions were examined in a retrospective study of 86 surgical cases with histologically confirmed Graves' disease. Operation resulted in euthyroidism in 76% of cases. Recurrent thyrotoxicosis appeared in 8%. Hypothyroidism developed in 14 patients (16%), all with estimated remnant weights of less than 8 gm. In each case, hypothyroidism was diagnosed within the first postoperative year. The capability for early diagnosis of hypothyroidism, however, is a significant advantage of surgical treatment. Within the range of estimated remnant weights, a significant and negative correlation was found between remnant size and the subsequent development of hypothyroidism, but neither euthyroidism nor recurrence of thyrotoxicosis could be correlated with remnant size. In the individual patient, therefore, estimated remnant size is of limited value in predicting future thyroid function.

Mature (450 g) rats were subjected to food restriction (60 percent of usual intake) with or without weight cycling (produced by cycles of 3 days of fasting followed by 7 days of refeeding). Weight cycling did not affect body weight, body composition, or food efficiency during the restriction period. However, the group subjected to weight cycling (WC) had an elevated level of lipoprotein lipase (LPL) activity in the epididymal adipose tissue as compared to the group receiving a constant amount of food each day (CO). After 40 days (four 10-day cycles) of food restriction, rats were allowed ad-libitum access to a stock diet for 18 days. WC rats restored carcass energy more rapidly, with a greater food efficiency than CO rats. Carcass energy was not totally restored at the end of the 18-day period, but WC rats had regained significantly more total carcass energy and total fat-free dry weight (FFDW) than CO rats. Food intake during refeeding did not differ significantly between WC and CO rats. These results suggest that weight cycling in a food-restricted program has the potential to increase food efficiency during a subsequent refeeding period.

A model of energy-nitrogen balance developed in animals was adapted to the study of human bioenergetics. By creating balance conditions and steady-state formula infusion rates, each of the needed components of energy and nitrogen balance can now be measured with a high level of accuracy. A comprehensive description of energetic efficiency at the whole body level is possible using appropriate mathematical modeling. Key questions in human bioenergetics await these results, and our laboratory is currently undertaking these studies.