Fat and carbohydrate overfeeding in humans: different effects on energy storage

Horton, Tracy J.; Drougas, H. J.; Brachey, A; Reed, George W.; Peters, John C.; Hill, James O.

doi:10.1093/ajcn/62.1.19

Cited by 302 publications

(195 citation statements)

References 28 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…The ability to switch on fat oxidation in response to an increase in dietary fat is variable between subjects and may translate to a positive fat balance and weight gain over time (24). Furthermore, an impaired ability to oxidize fatty acids is postulated to increase intramyocellular triglycerides and other lipid intermediates in the cell, which interfere with insulin signaling (25,26).…”

Section: Discussionmentioning

confidence: 99%

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

et al. 2007

View full text Add to dashboard Cite

Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n ‫؍‬ 8) and in ageand fatness-matched individuals with a strong family history of type 2 diabetes (n ‫؍‬ 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P < 0.05). This was related to impaired activation of genes involved in lipid metabolism, including those for peroxisome proliferator-activated receptor coactivator-1␣ (PGC1␣) and fatty acid translocase (FAT)/CD36 (P < 0.05). Of interest, adiponectin receptor-1 expression decreased 23% after the high-fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1␣ and FAT/CD36 are likely candidates in mediating this response. Diabetes 56: [2046][2047][2048][2049][2050][2051][2052][2053] 2007 R elatives of individuals with type 2 diabetes are an ideal human model to test for mechanisms in the early development of insulin resistance because approximately two-thirds eventually develop diabetes, and they can be tested before the development of other confounding factors, including hyperglycemia, dyslipidemia, and changes in insulin secretion (1). Insulin-resistant relatives will also develop impaired lipid metabolism, including increased circulating free fatty acids (FFAs) (2), accumulation of triglycerides and other lipid moieties within skeletal muscle (3), and postprandial hypertriglyceridemia (4). However, the mechanism(s) responsible for these early defects in lipid metabolism is not completely elucidated, although we and others suggest that intramuscular triglyceride accumulation may occur secondary to the development of insulin resistance (3,5).In lean individuals, increasing the proportion of dietary fat switches on fatty acid oxidation, whereas the infusion of glucose and insulin promotes carbohydrate oxidation. The cellular capacity to switch from lipid to carbohydrate and vice versa has been termed "metabolic flexibility," and there is large variation in this parameter between individuals (6). Obese and weight-reduced obese individuals have impaired metabolic flexibility on a whole-body level (7). Fatty acid...

show abstract

Section: Discussionmentioning

confidence: 99%

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

et al. 2007

View full text Add to dashboard Cite

show abstract

“…This result is in general agreement with observations using indirect calorimetry showing that addition of excess dietary fat had little impact on macronutrient oxidation rates in comparison with dietary carbohydrate or protein. 1,13,14 Glycogen changes can impact the macronutrient oxidation rates, but these effects are limited to only a few days after which glycogen achieves a new equilibrium. Therefore, our model responds correctly after that time period as illustrated by comparisons with the macronutrient oxidation data in Figures 3 and 4.…”

Section: Discussionmentioning

confidence: 99%

How adaptations of substrate utilization regulate body composition

2007

View full text Add to dashboard Cite

Objective: To elucidate the mathematical relationship between longitudinal changes of body composition and the adaptations of substrate utilization required to produce those changes. Design: We developed a simple mathematical model of macronutrient balance. By using an empirical relationship describing lean body mass as a function of fat mass, we derived a mathematical expression for how substrate utilization adapts to changes of diet, energy expenditure and body fat such that energy imbalances produced the required changes of body composition. Results: The general properties of our model implied that short-term changes of dietary fat alone had little impact on either fat or non-fat oxidation rates, in agreement with indirect calorimetry data. In contrast, changes of non-fat intake caused robust adaptations of both fat and non-fat oxidation rates. Without fitting any model parameters, the predicted body composition changes and oxidation rates agreed with experimental studies of overfeeding and underfeeding when the measured food intake, energy expenditure and initial body composition were used as model inputs. Conclusion: This is the first report to define the quantitative connection between longitudinal changes of body composition and the required relationship between substrate utilization, diet, energy expenditure and body fat mass. The mathematical model predictions are in good agreement with experimental data and provide the basis for future study of how changes of substrate utilization impact body composition regulation.

show abstract

“…As a result, calorie per calorie, the theoretical excess energy storage will be lower with CHO overfeeding as compared to fat overfeeding. 19 When saturation of glycogen stores occurs the diversion of excess CHO into fat will be operating as a virtual 'sink' process or a sort of safety valve. 12 It is necessary to dispose of the excessive exogenous CHO, since this is limited by the magnitude of the oxidation process in the tissues consuming glucose.…”

Section: Fat Balance and De Novo Lipogenesis Y Schutzmentioning

confidence: 99%

Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis

Schütz

2004

Int J Obes

View full text Add to dashboard Cite

The measurement of fat balance (fat input minus fat output) involves the accurate estimation of both metabolizable fat intake and total fat oxidation. This is possible mostly under laboratory conditions and not yet in free-living conditions. In the latter situation, net fat retention/mobilization can be estimated based on precise and accurate sequential body composition measurements. In case of positive balance, lipids stored in adipose tissue can originate from dietary (exogenous) lipids or from nonlipid precursors, mainly from carbohydrates (CHOs) but also from ethanol, through a process known as de novo lipogenesis (DNL). Basic equations are provided in this review to facilitate the interpretation of the different subcomponents of fat balance (endogenous vs exogenous) under different nutritional circumstances. One difficulty is methodological: total DNL is difficult to measure quantitatively in man; for example, indirect calorimetry only tracks net DNL, not total DNL. Although the numerous factors (mostly exogenous) influencing DNL have been studied, in particular the effect of CHO overfeeding, there is little information on the rate of DNL in habitual conditions of life, that is, large day-to-day fluctuations of CHO intakes, different types of CHO ingested with different glycemic indexes, alcohol combined with excess CHO intakes, etc. Three issues, which are still controversial today, will be addressed: (1) Is the increase of fat mass induced by CHO overfeeding explained by DNL only, or by decreased endogenous fat oxidation, or both? (2) Is DNL different in overweight and obese individuals as compared to their lean counterparts? (3) Does DNL occur both in the liver and in adipose tissue? Recent studies have demonstrated that acute CHO overfeeding influences adipose tissue lipogenic gene expression and that CHO may stimulate DNL in skeletal muscles, at least in vitro. The role of DNL and its importance in health and disease remain to be further clarified, in particular the putative effect of DNL on the control of energy intake and energy expenditure, as well as the occurrence of DNL in other tissues (such as in myocytes) in addition to hepatocytes and adipocytes.

show abstract

Fat and carbohydrate overfeeding in humans: different effects on energy storage

Cited by 302 publications

References 28 publications

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

How adaptations of substrate utilization regulate body composition

Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis

Contact Info

Product

Resources

About