Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men

Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men1–3 Iva Marques-Lopes, Diana Ansorena, Iciar Astiasaran, Luis Forga, and J Alfredo Martínez ABSTRACT Background: Adjustments of carbohydrate intake and oxidation occur in both normal-weight and overweight individuals. Nevertheless, the contribution of carbohydrates to the accumulation of fat through either reduction of fat oxidation or stimulation of fat synthesis in obesity remains poorly investigated. Objective: The objective of this study was to assess the postprandial metabolic changes and the fractional hepatic de novo lipogenesis (DNL) induced by a high-carbohydrate, low-fat meal in lean and overweight young men. Design: A high-carbohydrate, low-fat meal was administered to 6 lean and 7 overweight men after a 17.5-h fast. During the fasting and postprandial periods, energy expenditure (EE), macronutrient oxidation, diet-induced thermogenesis, and serum insulin, glucose, triacylglycerol, and fatty acids were measured. To determine DNL, [1-13C]sodium acetate was infused and the mass isotopomer distribution analysis method was applied. Results: After intake of the high-carbohydrate meal, the overweight men had hyperinsulinemia and higher fatty acid and triacylglycerol concentrations than did the lean men. The overweight group showed a greater EE, whereas there was no significant difference in carbohydrate oxidation between the groups. Nevertheless, the overweight men had a marginally higher protein oxidation and a lower lipid oxidation than did the lean men. DNL was significantly higher before and after meal intake in the overweight men and was positively associated with fasting serum glucose and insulin concentrations. Furthermore, postprandial DNL was positively correlated with body fat mass, EE, and triacylglycerol. Conclusion: After a high-carbohydrate, low-fat meal, overweight men had a lower fat oxidation and a higher fractional hepatic fat synthesis than did lean men. Am J Clin Nutr 2001;73:253–61. KEY WORDS Obesity, hyperinsulinemia, carbohydrates, fuel metabolism, fractional hepatic de novo lipogenesis, overweight men, lean men, diet-induced thermogenesis, energy expenditure, triacylglycerol, fractional hepatic fat synthesis INTRODUCTION The stability of body composition requires that intakes of protein, carbohydrate, and fat are balanced in terms of macronutrient oxidation over time (1, 2). Mechanisms such as postprandial endocrine and metabolic signals arise to give high priority to the adjustment of carbohydrate oxidation to carbohydrate availability (3). In this way, glycogen stores appear to determine the contribution of glucose to the oxidized fuel mix, which influences the rate of protein and fat oxidation (4). Despite this acute and precise regulation, carbohydrate consumption reduces the need to use fat as fuel, so carbohydrate is important in controlling the balance between fat intake and fat oxidation (5). Thus, the level of adiposity may be affected if short-term meal-related factors are sustained over long periods (6). Obesity is a multifactorial and complex disorder that is characterized by a long-term energy intake above energy expenditure (EE) (7). Many studies examined the regulation of these 2 components to provide an understanding of energy balance in overweight men. In this context, it is well known that fatty acid synthesis is stimulated by high-carbohydrate, low-fat diets in both animals and humans (8–10), but it is generally thought that de novo lipogenesis (DNL) is a quantitatively unimportant metabolic pathway in weight-stable men (11). Nevertheless, DNL may be higher in overweight hyperinsulinemic men than in lean men, depending on the type of carbohydrate in the diet (12). A widely used technique for assessing in vivo DNL has been indirect calorimetry, which allows estimation of the net conversion of carbohydrate to fat, because DNL is the only metabolic process with a respiratory quotient > 1; however, indirect calorimetry measures only net DNL and not the flux through the pathway (11). Glycogen storage was shown to represent the major fate of excess dietary carbohydrate after large carbohydrate loads from a single meal (13, 14) or from several days of surplus intake of energy as carbohydrate (15), showing a minor quantitative role for DNL in the day-to-day storage of surplus energy. In the past few years, new isotopic methods for studying human hepatic DNL in vivo were developed by measuring the incorpora- 1 From the Departments of Physiology and Nutrition and of Food Science, University of Navarra, Pamplona, Spain. 2 Supported by the Linea Especial en Nutrición y Obesidad (Special Investigation Project on Nutrition and Obesity), University of Navarra, and Gobierno de Navarra (project 1/98 de OF 32/98). 3 Address reprint requests to JA Martínez, Department of Physiology and Nutrition, University of Navarra, C/Irunlarrea s/n, 31008 Pamplona, Spain. E-mail: . Received December 21, 1999. Accepted for publication July 28, 2000. Am J Clin Nutr 2001;73:253–61. Printed in USA. © 2001 American Society for Clinical Nutrition 253 254 MARQUES-LOPES ET AL TABLE 1 Characteristics of the 13 young male participants1 Variable Lean (n = 6) Overweight (n = 7) Age (y) Height (m) Weight (kg) BMI (kg/m2) Percentage body fat (%) Body fat (kg) Fat-free mass (kg) 1– x ± SEM. 22.1 1.74 ± 0.01 63.5 ± 2.8 20.8 ± 0.7 15.4 ± 1.6 9.9 ± 1.3 53.6 ± 2.1 20.5 1.76 ± 0.01 96.1 ± 6.212 30.8 ± 1.72 26.7 ± 1.22 26.1 ± 3.02 69.9 ± 3.32 2 Significantly different from lean, P < 0.01. tion of [1-13C]sodium acetate into plasma VLDL fatty acids, which specifically determines the hepatic fraction of de novo synthesized VLDL palmitate (16, 17). Using this method (mass isotopomer distribution analysis; MIDA), several researchers studied the effects of isoenergetic low-fat, high-carbohydrate diets composed of simple and complex carbohydrates (10, 18) or during surplus or deficit carbohydrate diets (15). In these studies, a strong relation between carbohydrate intake and fractional DNL was found, but it remained quantitatively insignificant to the body fat stores. Nevertheless, these trials were performed in healthy nonobese men. Until now, only one study showed that DNL in obese men was correlated with body adiposity (19), but the factors influencing fatty acid synthesis in obese humans remain unclear. An understanding of the processes involved in the development of obesity is necessary so that strategies for its prevention and management can be designed. This can be facilitated by a better ability to identify individuals who are at risk of becoming obese, who may be characterized by a metabolic or genetic susceptibility to weight gain (20). The aim of this study was to determine the fractional hepatic DNL and the relation of this pathway with some metabolic and hormonal factors in lean and overweight men in response to a short fast (...truncated)