Jean-Pierre Flatt

Glycogen synthesis versus lipogenesis after a 500 gram carbohydrate meal in man.

The respiratory exchange and urinary nitrogen excretion of 6 healthy male subjects (age 21 +/- 1 yr; body weight 70 +/- 2 kg; means +/- SD) were followed for 10 hr after ingestion of a large amount of carbohydrates (CHO) in the form of bread, jam, and fruit juice, equivalent to 479 g of starch. Peak values for blood glucose (6.6 +/- 0.6 mM; mean +/- SEM) and plasma insulin (139 +/- 26 microU/ml) were reached after 90 min at which time the nonprotein respiratory quotient (NP-RQ) had risen to 0.97. During the next 8 hr glucose levels remained near 5.5 mM while insulin declined gradually to 22 +/- 7 microU/ml. The average NP-RQ remained in the range of 0.91 to 0.98, though individual values exceeding 1.0 for very short periods were observed. The increase in energy expenditure above basal rates corresponded to a specific dynamic action (SDA) of 5.9 +/- 0.6%. Assuming the CHO load to be completely absorbed after 5 hr, and allowing for glucose oxidation calculated from the gas exchange data, the glycogen content of the subjects body tissue had then increased by 408 +/- 19 g. During the 10 hr after the meal, 133 g CHO, 17 g fat and 29 g protein were oxidized, providing respectively 66%, 19% and 15% of caloric expenditure, and leaving a gain in glycogen stores estimated at 346 +/- 12 g. The data imply that: (1) The capacity for glycogen storage in man in larger than generally believed, and (2) Fat synthesis from CHO will not exceed fat oxidation after one high-carbohydrate meal, even if it is uncommonly large. When a single high-carbohydrate meal is consumed, dietary CHO merely has the effect of reducing the rate of fat oxidation. These findings challenge the common perception that conversion of CHO to fat is an important pathway for the retention of dietary energy and for the accumulation of body fat.

Use and storage of carbohydrate and fat.

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 bodys 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 bodys 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.

Determination of optimal hyperalimentation infusion rate

Increased attention is being paid to the proper nutrition of critically ill surgical and medical patients. The effects of prolonged starvation or semistarvation on morbidity and mortality are well recognized [7, 14,261. Total parenteral nutrition (TPN) techniques [18, 291 and oral chemically defined diets [12, 34, 381 have made it possible to feed patients in most disease states. Indications for the use of these therapies have become widespread [I, 20, 22, 341. Most complications related to TPN are well recognized and their incidence can be reduced by the creation of hospital nutritional services that include interested staff, hyperalimentation nurse, therapeutic dietitian, and pharmacy. Proper guidelines have been developed for the management of central vein catheterrelated complications [36, 401, fluid and electrolyte, acid-base derangements [19, 37, 441 and septic complications [4, 16,431.

Body composition, respiratory quotient, and weight maintenance.

For weight maintenance, the fuel mix oxidized must match the nutrient distribution in the diet. The composition of the fuel mix oxidized and the respiratory quotient are influenced by circulating substrate and hormone concentrations, which, among other things, reflect the degree of replenishment of the bodys fuel reserves. Carbohydrate and protein balances are maintained without obvious changes in the bodys glycogen stores and protein pools. One of the most readily quantifiable measures by which to judge the effect of various inherited and circumstantial factors on energy metabolism and body composition is the percentage body fat for which weight maintenance occurs. The amount of body fat for which the steady state of weight maintenance tends to become established is therefore a key fact on which an understanding of body weight regulation should be based, rather than rates of energy turnover or past circumstances that may have led to fat accumulation, as often believed.

Corrective responses in human food intake identified from an analysis of 7-d food-intake records

BACKGROUND We tested the hypothesis that ad libitum food intake shows corrective responses over periods of 1-5 d. DESIGN This was a prospective study of food intake in women. METHODS Two methods, a weighed food intake and a measured food intake, were used to determine daily nutrient intake during 2 wk in 20 women. Energy expenditure with the use of doubly labeled water was done contemporaneously with the weighed food-intake record. The daily deviations in macronutrient and energy intake from the average 7-d values were compared with the deviations observed 1, 2, 3, 4, and 5 d later to estimate the corrective responses. RESULTS Both methods of recording food intake gave similar patterns of macronutrient and total energy intakes and for deviations from average intakes. The intraindividual CVs for energy intake ranged from +/-12% to +/-47% with an average of +/-25%. Reported energy intake was 85.5-95.0% of total energy expenditure determined by doubly labeled water. Significant corrective responses were observed in food intakes with a 3- to 4-d lag that disappeared when data were randomized within each subject. CONCLUSIONS Human beings show corrective responses to deviations from average energy and macronutrient intakes with a lag time of 3-4 d, but not 1-2 d. This suggests that short-term studies may fail to recognize important signals of food-intake regulation that operate over several days. These corrective responses probably play a crucial role in bringing about weight stability.

Differences in Basal Energy Expenditure and Obesity

Objective: To assess the impact of differences in basal energy expenditure on adiposity.

Issues and Misconceptions About Obesity

Energy is a concept of universal importance. In relation to body weight regulation, one is so used to consider energy intake, energy expenditure, and energy balance that one forgets that energy is an abstract notion without physiological equivalent. The body’s regulatory functions may strive to maintain carbohydrate (CHO), protein and/or fat balances, but not energy balance. The body ignores that 1 g of fat contains more than twice the energy present in 1 g of carbohydrate, an element of information needed to determine the energy balance. In applying this knowledge to consider body weight regulation, one introduces a biologically irrelevant fact. One may learn to be in awe at the body’s ability to maintain approximate energy balances over extended periods of an individual’s life, as a consequence of the organism’s ability to maintain substrate balances, but attempts to understand this as the result of a regulatory process directed at the energy balance itself are doomed to be frustrated. Not surprisingly, failure to be aware of the inappropriate use of the energy and energy balance concepts in considering body weight regulation and obesity has spawned numerous misconceptions (1). The intent of this article is to provide direct access to the considerations that pertain to particular notions commonly cited in the context of obesity. Their presentation under separate headings should be helpful, in particular to individuals not necessarily immersed in obesity research who want to understand the meaning of specific terms and concepts.

Day-to-Day Variation in Food Intake and Energy Expenditure in Healthy Women: The Dietitian II Study

Because day-to-day food intake varies, we tested the hypothesis that ad libitum food intake and energy expenditure show corrective responses over periods of 1 to 10 days in healthy young women. Food intake and accelerometry measurements were collected daily for 17 days in 15 young women. Total daily energy expenditure (TDEE) using doubly labeled water was also measured. The daily deviations in macronutrient and energy intake and energy expenditure from the average values were compared with the deviations observed over succeeding intervals to estimate the corrective responses. The intraindividual coefficients of variation for energy intake averaged ±25%, ranging from 16% to 34%. TDEE had a coefficient of variation of 8.3%, and accelerometry had a coefficient of variation of 8.4% (range=4.6% to 16.4%). Energy expenditure by accelerometry (2,087±191 kcal/day) was not significantly different from TDEE (2,128±177 kcal/day), but reported daily energy intake was 20.4% lower (1,693±276 kcal/day). There were significant corrective responses in energy from fat and total energy intake. This occurred from Days 3 to 6, with a peak at Day 5 that disappeared when data were randomized within each subject. Human beings show corrective responses to deviations from average energy and macronutrient intakes with a lag time of 3 to 6 days, but not 1 to 2 days. These corrective responses are likely to play a role in bringing about weight stability.

Effects of β-hydroxybutyrate, glycerol, and free fatty acid infusions on glucagon and epinephrine secretion in dogs during acute hypoglycemia

The importance of glucagon in the regulation of carbohydrate metabolism is clearly established. However, the role played by this hormone in the regulation of the overall fuel economy is less certain, particularly with respect to such nonglucose fuels as free fatty acids, glycerol, and ketoacids. In order to elucidate glucagons role with respect to the latter substrates, dogs were infused with solutions of these three fuels, and their A-cell responses to concomitant insulin-induced hypoglycemia were studied. In addition, epinephrine levels were also monitored. It was found that while these infusions failed to suppress glucagon release, the ketoacid infusion did significantly reduce epinephrine secretion during the insulin-induced hypoglycemic period. It was therefore concluded that glucagon secretion under these experimental conditions is not responsive to prevailing non-glucose fuel levels. Indeed, these data suggest that the sympathetic nervous system may play an important role in the regulation of the over-all fuel economy.

A protein sparing model in the rat during hypocaloric feeding: Factors determining preservation of visceral protein function

The requirements to spare total body protein during hypocaloric feeding in 102 342 ± 7-g rats were studied. Twelve rats were fasted; 12 had fasting supplemented by 478 ± 39 mg of nitrogen/day as crystalline amino acids. Twenty-four rats received 41 kcal/day as fat and 24 additional rats received isocaloric diets in which 13 cal as fat were replaced with 491 ± 40 mg of nitrogen as crystalline amino acids. All were compared to 30 animals maintained on a semisynthetic diet sufficient in both calories and protein ad libitum . Survival, liver weight and protein content, serum albumin, and delayed hypersensitivity response were dependent upon the availability of nonprotein calories either endogenously supplied or provided as dietary fat. Redistribution of body protein mass allowed a maintenance of adequate visceral function. The provision of dietary amino acids better preserved visceral function and total body nitrogen. For the rat to become a useful experimental model for investigating hypocaloric therapies, nonprotein calories are required.