Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets—Data from a Randomized Cross-Over Study in Healthy Subjects

Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.

Download Full-text

Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice

International Journal of Molecular Medicine ◽

10.3892/ijmm.2016.2831 ◽

2016 ◽

Vol 39 (2) ◽

pp. 407-414 ◽

Cited By ~ 14

Author(s):

Takumi Kawaguchi ◽

Takato Ueno ◽

Yoichi Nogata ◽

Masako Hayakawa ◽

Hironori Koga ◽

...

Keyword(s):

Oxidative Stress ◽

Amino Acid ◽

Wheat Bran ◽

High Fat Diet ◽

High Fat ◽

Alcoholic Steatohepatitis ◽

Branched Chain Amino Acid ◽

Branched Chain

Download Full-text

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz073 ◽

2019 ◽

Vol 110 (2) ◽

pp. 349-357 ◽

Cited By ~ 7

Author(s):

Stella Iacovides ◽

David Goble ◽

Bronwyn Paterson ◽

Rebecca M Meiring

Keyword(s):

Cognitive Function ◽

Sleep Quality ◽

Visual Learning ◽

Normal Weight ◽

Healthy Individuals ◽

High Fat ◽

Low Fat ◽

High Carbohydrate ◽

Cohen’S D ◽

Cohen's D

ABSTRACTBackgroundThe high-fat ketogenic diet (KD) has become an increasingly popular diet not only in overweight/obese populations, or those with clinical conditions, but also in healthy non-overweight populations.ObjectiveBecause there are concerns about the association between high-fat diets and cognitive decline, this study aimed to determine the effects of a KD compared with an isocaloric high-carbohydrate, low-fat (HCLF) diet on cognitive function, sleep, and mood in healthy, normal-weight individuals.MethodsEleven healthy, normal-weight participants (mean age: 30 ± 9 y) completed this randomized, controlled, crossover study. Participants followed 2 isocaloric diets—an HCLF diet (55% carbohydrate, 20% fat, and 25% protein) and a KD (15% carbohydrate, 60% fat, and 25% protein)—in a randomized order for a minimum of 3 wk, with a 1-wk washout period between diets. Measures of β-hydroxybutyrate confirmed that all participants were in a state of nutritional ketosis during post-KD assessments (baseline: 0.2 ± 0.2 mmol/L; KD: 1.0 ± 0.5 mmol/L; washout: 0.2 ± 0.1 mmol/L; and HCLF: 0.3 ± 0.2 mmol/L). Cognitive function was assessed using a validated, psychological computer-based test battery before and after each diet. Subjective measures of mood and sleep were also monitored throughout the study using validated scales.ResultsThree weeks of sustained nutritional ketosis, compared with the HCLF diet, had no effect on speed and accuracy responses in tasks designed to measure vigilance (speed: P = 0.39, Cohen's d = 0.26; accuracy: P = 0.99, Cohen's d = 0.04), visual learning and memory (speed: P = 0.99, Cohen's d = 0.04; accuracy: P = 0.99, Cohen's d = 0.03), working memory (speed: P = 0.62, Cohen's d = 0.26; accuracy: P = 0.98, Cohen's d = 0.07), and executive function (speed: P = 0.60, Cohen's d = 0.31; accuracy: P = 0.90, Cohen's d = 0.19). Likewise, mood, sleep quality, and morning vigilance did not differ (P > 0.05) between the dietary interventions.ConclusionThe results of our randomized, crossover, controlled study suggest that 3 wk of sustained nutritional ketosis had no effect on cognitive performance, mood, or subjective sleep quality in a sample of healthy individuals. This trial was registered in the Pan African Clinical Trial Registry as PACTR201707002406306.

Download Full-text

Time course of effects of preloads high in fat or carbohydrate on food intake and hunger ratings in humans

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.4.r756 ◽

1991 ◽

Vol 260 (4) ◽

pp. R756-R763 ◽

Cited By ~ 15

Author(s):

B. J. Rolls ◽

S. Kim ◽

A. L. McNelis ◽

M. W. Fischman ◽

R. W. Foltin ◽

...

Keyword(s):

Food Intake ◽

Time Course ◽

Delay Condition ◽

Normal Weight ◽

Time Interval ◽

Physiological Effects ◽

High Fat ◽

Macronutrient Composition ◽

High Carbohydrate ◽

Self Selection

A high-carbohydrate (CHO) yogurt (81% CHO) and a high-fat yogurt (65% fat), containing similar levels of protein, were given in equal volumes as preloads to 14 normal-weight, nondieting males and 14 normal-weight, nondieting females. The yogurts were formulated to have similar energy densities and sensory properties, so that differences in responses to the preloads would depend on postingestive physiological effects. Three intervals (30, 90, and 180 min) between the preloads and a self-selection meal consisting of a variety of foods were utilized. The self-selection meal was served at the subject's normal lunchtime under all conditions. In the 30-min-delay condition, subjects accurately compensated for the calories in the preloads compared with a no-preload condition, but as the interval increased, compensation was less precise. No significant differences in subsequent food intake were found between the high-CHO and high-fat yogurts at any time interval. Also, there were no differences in ratings of hunger and fullness between the yogurts. The macronutrient composition of the preloads did not affect the types of foods, or macronutrients, consumed at lunch.

Download Full-text

Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity

Metabolites ◽

10.3390/metabo11060392 ◽

2021 ◽

Vol 11 (6) ◽

pp. 392

Author(s):

Ueli Bütikofer ◽

David Burnand ◽

Reto Portmann ◽

Carola Blaser ◽

Flurina Schwander ◽

...

Keyword(s):

Amino Acids ◽

Branched Chain Amino Acids ◽

Normal Weight ◽

Dependent Manner ◽

Metabolic Dysfunction ◽

High Fat ◽

Randomized Controlled ◽

Two Factors ◽

Branched Chain ◽

Dose Dependent

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity.

Download Full-text

Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-00475 ◽

2017 ◽

Vol 102 (7) ◽

pp. 2473-2481 ◽

Cited By ~ 24

Author(s):

Domenico Tricò ◽

Hetty Prinsen ◽

Cosimo Giannini ◽

Robin de Graaf ◽

Christoph Juchem ◽

...

Keyword(s):

Amino Acid ◽

Glycemic Control ◽

Branched Chain Amino Acid ◽

Amino Acid Levels ◽

Branched Chain

Download Full-text

Impact of Branched Chain Amino Acid Supplementation on Hepatic Mitochondrial Metabolism in Mice with Non-alcoholic Fatty Liver Disease (P08-136-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-136-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Muhammed Muyyarikkandy ◽

Meghan Maguire ◽

Christine Zhang ◽

Nathan Kattapuram ◽

Vaishna Muralidaran ◽

...

Keyword(s):

Gene Expression ◽

Liver Disease ◽

Fatty Liver Disease ◽

Mitochondrial Protein ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Branched Chain Amino Acid ◽

Mitochondrial Lipid ◽

Branched Chain ◽

Alcoholic Fatty Liver Disease

Abstract Objectives Elevated circulating branched chain amino acid (BCAA) levels are correlated with the development of insulin resistance and type 2 diabetes mellitus in humans. On the other hand, BCAA supplementation has been shown to be beneficial in improving insulin resistance during chronic liver disease. Furthermore, there is recent evidence of significant crosstalk between BCAA and mitochondrial lipid metabolism. Considering the central role of dysfunctional mitochondrial lipid metabolism in diet-induced obesity and non-alcoholic fatty liver disease (NAFLD), our objective was to determine the impact of dietary BCAA supplementation on hepatic mitochondrial function, in a diet-induced mouse model of NAFLD. We hypothesized that the dietary supplementation of BCAA, together with a high fat diet, will exacerbate hepatic mitochondrial dysfunction during NAFLD. Methods C57BL/6NJ mice were fed with a control (10% kcal fat), high fat (HF; 60% kcal fat), or HF diet supplemented with BCAA (BA; 60% kcal fat; 1.5X BCAA) diet for 16 weeks. Livers from these mice were used for mitochondrial isolation, total liver and mitochondrial protein estimation, determination of amino acids and Kreb's cycle intermediates by mass spectrometry, and gene expression profiles. Results While the liver weights (g ± SEM) of HF fed mice (2.6 ± 0.36) were significantly higher than the control mice (1.5 ± 0.19), BCAA supplemented mice had significantly lower liver weights than the HF fed mice (1.8 ± 0.28). Hepatic mitochondrial protein content (µg/g liver ± SEM) was enriched in BCAA supplemented mice compared to their HF diet fed counterparts (BA, 3858 ± 476; HF, 2635 ± 394; P ˂ 0.05). Many of the organic acid intermediates of the Kreb's cycle were significantly lower in the liver of HF fed mice. Interestingly, BCAA supplementation (BA) with HF feeding restored hepatic organic acid intermediates to similar levels observed in control mice. Further, HF and BA feeding, both downregulated lipogenic gene expression (e.g., Fasn, Scd1, Acly) in the liver. Conclusions Our results suggest that BCAA supplementation enhanced hepatic mitochondrial biogenesis and oxidative metabolism in the liver of mice with NAFLD. High-fat diets which significantly suppressed the rates of de novo lipogenesis, could have provided the BCAAs, a metabolic milieu favorable for the induction of mitochondrial activity. Funding Sources National Institutes of Health (R01).

Download Full-text

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

Infection and Immunity ◽

10.1128/iai.02579-14 ◽

2014 ◽

Vol 83 (1) ◽

pp. 173-183 ◽

Cited By ~ 23

Author(s):

Gael Gesbert ◽

Elodie Ramond ◽

Fabiola Tros ◽

Julien Dairou ◽

Eric Frapy ◽

...

Keyword(s):

Amino Acid ◽

Critical Role ◽

Cell Types ◽

Host Cells ◽

Metabolic Adaptation ◽

Amino Acid Transporters ◽

Loss Of Function ◽

Content Type ◽

Branched Chain Amino Acid ◽

Branched Chain

Intracellular bacterial pathogens have adapted their metabolism to optimally utilize the nutrients available in infected host cells. We recently reported the identification of an asparagine transporter required specifically for cytosolic multiplication ofFrancisella. In the present work, we characterized a new member of the major super family (MSF) of transporters, involved in isoleucine uptake. We show that this transporter (here designated IleP) plays a critical role in intracellular metabolic adaptation ofFrancisella. Inactivation of IleP severely impaired intracellularF. tularensissubsp.novicidamultiplication in all cell types tested and reduced bacterial virulence in the mouse model. To further establish the importance of theilePgene inF. tularensispathogenesis, we constructed a chromosomal deletion mutant ofileP(ΔFTL_1803) in theF. tularensissubsp.holarcticalive vaccine strain (LVS). Inactivation of IleP in theF. tularensisLVS provoked comparable intracellular growth defects, confirming the critical role of this transporter in isoleucine uptake. The data presented establish, for the first time, the importance of isoleucine utilization for efficient phagosomal escape and cytosolic multiplication ofFrancisellaand suggest that virulentF. tularensissubspecies have lost their branched-chain amino acid biosynthetic pathways and rely exclusively on dedicated uptake systems. This loss of function is likely to reflect an evolution toward a predominantly intracellular life style of the pathogen. Amino acid transporters should be thus considered major players in the adaptation of intracellular pathogens.

Download Full-text

The Differences in Postprandial Serum Concentrations of Peptides That Regulate Satiety/Hunger and Metabolism after Various Meal Intake, in Men with Normal vs. Excessive BMI

Nutrients ◽

10.3390/nu11030493 ◽

2019 ◽

Vol 11 (3) ◽

pp. 493 ◽

Cited By ~ 5

Author(s):

Edyta Adamska-Patruno ◽

Lucyna Ostrowska ◽

Joanna Goscik ◽

Joanna Fiedorczuk ◽

Monika Moroz ◽

...

Keyword(s):

Body Weight ◽

Normal Weight ◽

Serum Concentrations ◽

High Fat ◽

Obese People ◽

High Carbohydrate ◽

Meal Intake ◽

Total Ghrelin ◽

Normal Body Weight ◽

Challenge Tests

The energy balance regulation may differ in lean and obese people. The purposes of our study were to evaluate the hormonal response to meals with varying macronutrient content, and the differences depending on body weight. Methods. The crossover study included 46 men, 21–58 years old, normal-weight and overweight/obese. Every subject participated in two meal-challenge-tests with high-carbohydrate (HC), and normo-carbohydrate (NC) or high-fat (HF) meals. Fasting and postprandial blood was collected for a further 240 min, to determine adiponectin, leptin and total ghrelin concentrations. Results. In normal-weight individuals after HC-meal we observed at 60min higher adiponectin concentrations (12,554 ± 1531 vs. 8691 ± 1070 ng/mL, p = 0.01) and significantly (p < 0.05) lower total ghrelin concentrations during the first 120 min, than after HF-meal intake. Fasting and postprandial leptin levels were significantly (p < 0.05) higher in overweigh/obese men. Leptin concentrations in normal-weight men were higher (2.72 ± 0.8 vs. 1.56 ± 0.4 ng/mL, p = 0.01) 180 min after HC-meal than after NC-meal intake. Conclusions. Our results suggest that in normal-body weight men we can expect more beneficial leptin, adiponectin, and total ghrelin response after HC-meal intake, whereas, in overweight/obese men, the HC-meal intake may exacerbate the feeling of hunger, and satiety may be induced more by meals with lower carbohydrate content.

Download Full-text