The effect of glucocorticoid administration on energy metabolism and food intake was studied in 20 healthy, nondiabetic Caucasian male volunteers [27 +/- 5 (SD) yr, 72 +/- 9 kg, 20 +/- 7% body fat] randomly and blindly assigned to glucocorticoid (methylprednisolone, METH; n = 10) or placebo (PLAC; n = 10) treatment. Each subject was studied twice: during a weight maintenance diet and during ad libitum food intake. Energy metabolism was measured by indirect calorimetry and food intake by an automated food-selection system. Twenty-four-hour urinary norepinephrine excretion (24-h NE) was used as an estimate of sympathetic nervous system activity. During weight maintenance, METH intravenous infusion (125 mg/30 min) increased energy expenditure compared with PLAC, and after 4 days of oral therapy, METH (40 mg/day) decreased 24-h NE and increased energy expenditure compared with PLAC. During ad libitum food intake, after 4 days of METH (40 mg/day) or PLAC oral therapy, both groups increased their energy intake over weight maintenance, but the increase was significantly larger in the METH group compared with the PLAC group (4,554 +/- 1,857 vs. 2,867 +/- 846 kcal/day; P = 0.04). Our data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of glucocorticoids to act directly or indirectly on the central regulation of appetite.

To study the effect of dietary fat on postprandial substrate utilization and nutrient balance, respiratory exchange was determined in seven young men for 1 h before and 9 h after the ingestion of one of three different breakfasts: i.e., bread, jam, and dried meat (482 kcal: 27% protein, 62% carbohydrate, and 11% fat); bread, jam, and dried meat plus 50 g of margarine containing long-chain triglycerides (LCT); or bread, jam, and dried meat plus 40 g medium-chain triglycerides (MCT) and 10 g LCI margarine (858 kcal: 15% protein, 35% carbohydrate, and 50% fat).Plasma glucose concentrations peaked 45 min after the start of the meals. When compared with the low fat meal, the LC1T margarine supplement had no effect at any time on circulating glucose and insulin concentrations, nor on the respiratory quotient. When MCIrs were consumed, plasma glucose and insulin concentrations remained lower and plasma FFA concentrations higher during the first 2 h. 9 h after the breakfasts, the amounts of substrates oxidized were similar in each case, i.e., -320, 355, and 125 kcal for carbohydrate, fat, and protein, respectively. This resulted in comparable carbohydrate (mean±SD = -22±32, -22±37, and -24±22 kcal) and protein balances (-7±9, +7±7, and -8±11 kcal) after the low fat, LCT-and MCI-supplemented test meals, respectively. However, after the low fat meal, the lipid balance was negative (-287±60 kcal), which differed significantly (P < 0.001) from the fat balances after the LCT-and MCT-supplemented meals, i.e., +60±33 and +57±25 kcal, respectively. The results demonstrate that the rates of fat and of carbohydrate oxidation are not influenced by the fat content of a meal.

In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO load (r = 0.82) and between net lipogenesis and the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.

Starch, sugars, and triglycerides provide the bulk of dietary energy. To preserve homeostasis, most of the glucose and fat absorbed must be stored to be mobilized later at rates appropriate to bring about the oxidation of a fuel mix matching on average the macronutrient distribution in the diet. The body's glycogen stores are so small that regulatory mechanisms capable of efficiently adjusting carbohydrate oxidation to carbohydrate intake have developed through evolution. Fat oxidation is regulated primarily by events pertaining to the body's carbohydrate economy, rather than by fat intake. Adjustment of fat oxidation to intake occurs because cumulative errors in the fat balance lead over time to changes in adipose tissue mass, which can substantially alter free fatty acid concentration, insulin sensitivity, and fat oxidation. Fat intake and habitual glycogen concentrations are important in determining how fat one has to be to oxidize as much fat as one eats.