Kevin Seyssel

An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men

The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure.

Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance

Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1−/− mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1−/− only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.

Effects of a breakfast spread out over time on the food intake at lunch and the hormonal responses in obese men.

The effects of frequent eating on health and particularly on appetite and metabolism are unclear. We have previously shown that frequent eating decreased appetite and energy intake at the subsequent meal in lean men. In the present study, we tested the same pattern in obese subjects. Seventeen obese men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180min (F4), followed by an ad libitum buffet (T240) in an experimental restaurant. Subjects rated their appetite throughout the sessions. (ii) two sessions consisting of the same breakfasts F1 and F4 in a Clinical Centre, followed by a standardized meal. Blood sampling was performed to study ghrelin, glucagon-like peptide-1 (GLP-1), and metabolic kinetics. Indirect calorimetry measurements were performed. After F4, at T240min, ghrelin concentration (P=0.03) and hunger ratings (P<0.001) were lower while GLP-1 concentration (P=0.006) and satiety ratings (P=0.02) were higher. In F4, subjects consumed at the buffet, less food in grams (P=0.04) and less energy from low energy dense foods (P=0.01), but total energy intakes were not different between conditions. In F4, the area under the curve was lower for insulin (P=0.02) and non-esterified fatty acids (NEFA) (P=0.03). Diet induced thermogenesis was reduced in F4 (P=0.03) between T0 and T240. Even if subjective and physiological data suggest a beneficial effect of frequent eating on appetite in obese men, no effect was demonstrated on energy intake. Moreover, the decrease in diet induced thermogenesis and lipolysis, reflected by NEFA profiles, could be deleterious on energy balance in the long run.

Regulation of Energy Metabolism and Mitochondrial Function in Skeletal Muscle During Lipid Overfeeding in Healthy Men

CONTEXT/OBJECTIVE The aim of this study was to evaluate the regulation of the fuel partitioning and energy metabolism in skeletal muscle during lipid overfeeding in healthy men. Design/Participants/Intervention: Thirty-nine healthy volunteers were overfed for 56 days with a high-fat diet (3180 kJ/d). Energy metabolism (indirect calorimetry) was characterized in the fasting state and during a test meal before and at the end of the diet. Skeletal muscle biopsies were taken at day 0 and day 56. MAIN OUTCOME MEASURES Change in gene expression, mitochondrial respiration, nicotinamide adenine dinucleotide (NAD(+)) content, and acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in skeletal muscle was measured. RESULTS Overfeeding increased body weight (+2.6 kg) and fat mass concomitantly with a shift in the use of substrates as energy fuel toward preferential oxidation of carbohydrates instead of lipids. Changes in lipid metabolic gene expression supported this observation, with a reduction in pyruvate dehydrogenase kinase 4 expression that could be the consequences of decreased NAD(+) concentration and reduced deacetylase activity of the sirtuins, as supported by hyperacetylation of PGC-1α after overfeeding. Interestingly, this reduction of the sirtuin PGC-1α pathway was associated with increased mitochondrial gene expression and higher respiration rate under these conditions. CONCLUSION Adaptation to lipid overfeeding and regulation of fuel partitioning in human muscle appear to rely on a dissociation between the regulatory functions of the sirtuin-PGC-1α pathway on fatty acid oxidation and on mitochondrial regulation. This may facilitate lipid storage during a period of positive energy balance while maintaining mitochondrial functions and oxidative capacities.

Plasma acyl-ghrelin increases after meal initiation: a new insight.

Background/Objectives:Plasma ghrelin secretion over time in humans is characterized by pre-prandial increases and by post-prandial decreases all day long. However, some authors who measured ghrelin concentrations around meals showed a rise in plasma ghrelin concentration after meal initiation followed by the typical post-prandial decrease. In order to confirm this observation that has never been discussed, we described ghrelin profiles around four eating episodes in the morning in adult men.Subjects/Methods:Twenty normal-weight and 17 obese men were instructed to eat four fixed meals (706 kJ) 10 min long at 0800 h, 0900 h, 1000 h and 1100 h. Using frequent blood sampling, we determined plasma acyl-ghrelin concentrations around those eating episodes. Glucose, insulin and GLP-1 concentrations were also measured.Results:The meals consumption induced a significant increase in plasma acyl-ghrelin concentrations 10 min after meal initiation (P<0.0001): +20.9±5.8 and +10.7±3.3 pg/ml in normal-weight and obese subjects for the first meal; +10.4±3.0 and +5.5±3.9 pg/ml in normal-weight and obese subjects for the second meal; +12.4±3.6 and +4.2±2.1 pg/ml in normal-weight and obese subjects for the third meal; and +4.4±4.1 and +3.3±2.61 pg/ml in normal-weight and obese subjects for the fourth meal.Conclusions:This study is the first to describe and discuss the post-meal initiation ghrelin increase. This finding is consistent in normal-weight and obese individuals.

Fructose overfeeding in first-degree relatives of type 2 diabetic patients impacts energy metabolism and mitochondrial functions in skeletal muscle.

SCOPE The aim of the study was to assess the effects of a high-fructose diet (HFrD) on skeletal muscle transcriptomic response in healthy offspring of patients with type 2 diabetes, a subgroup of individuals prone to metabolic disorders. METHODS AND RESULTS Ten healthy normal weight first-degree relatives of type 2 diabetic patients were submitted to a HFrD (+3.5 g fructose/kg fat-free mass per day) during 7 days. A global transcriptomic analysis was performed on skeletal muscle biopsies combined with in vitro experiments using primary myotubes. Transcriptomic analysis highlighted profound effects on fatty acid oxidation and mitochondrial pathways supporting the whole-body metabolic shift with the preferential use of carbohydrates instead of lipids. Bioinformatics tools pointed out possible transcription factors orchestrating this genomic regulation, such as PPARα and NR4A2. In vitro experiments in human myotubes suggested an indirect action of fructose in skeletal muscle, which seemed to be independent from lactate, uric acid, or nitric oxide. CONCLUSION This study shows therefore that a large cluster of genes related to energy metabolism, mitochondrial function, and lipid oxidation was downregulated after 7 days of HFrD, thus supporting the concept that overconsumption of fructose-containing foods could contribute to metabolic deterioration in humans.

Comparison of MRI-derived vs. traditional estimations of fatty acid composition from MR spectroscopy signals

The composition of fatty acids in the body is gaining increasing interest, and can be followed up noninvasively by quantitative magnetic resonance spectroscopy (MRS). However, current MRS quantification methods have been shown to provide different quantitative results in terms of lipid signals, with possible varying outcomes for a given biological examination. Quantitative magnetic resonance imaging using multigradient echo sequence (MGE‐MRI) has recently been added to MRS approaches. In contrast, these methods fit the undersampled magnetic resonance temporal signal with a simplified model function (expressing the triglyceride [TG] spectrum with only three TG parameters), specific implementations and prior knowledge. In this study, an adaptation of an MGE‐MRI method to MRS lipid quantification is proposed.

Fructose use in clinical nutrition: metabolic effects and potential consequences

Purpose of review The current article presents recent findings on the metabolic effects of fructose. Recent findings Fructose has always been considered as a simple ‘caloric’ hexose only metabolized by splanchnic tissues. Nevertheless, there is growing evidence that fructose acts as a second messenger and induces effects throughout the human body. Summary Recent discoveries made possible with the evolution of technology have highlighted that fructose induces pleiotropic effects on different tissues. The fact that all these tissues express the specific fructose carrier GLUT5 let us reconsider that fructose is not only a caloric hexose, but could also be a potential actor of some behaviors and metabolic pathways. The physiological relevance of fructose as a metabolic driver is pertinent regarding recent scientific literature.

Breath acetone as a marker of energy balance: an exploratory study in healthy humans

An exploratory study was performed on eight healthy volunteers to assess how short-term changes in energy balance and dietary carbohydrate content impact breath acetone concentrations. Participants were studied on three occasions: on each occasion, they remained fasted and in resting conditions during the first 2 h to assess basal breath acetone and blood beta-hydroxybutyrate (BOHB). During the next 6 h, they remained fasted on one occasion (F), or were fed hourly high carbohydrate (HC) or low-carbohydrate (LC) meals to induce a positive energy balance on the other two occasions. They remained in resting conditions during 4 h, then performed a 2-hour low intensity exercise (25 W) inducing a negative energy balance. In resting conditions, breath acetone and blood BOHB concentrations increased progressively compared to basal values in F, but decreased and remained low throughout the test in HC. With LC, breath acetone increased progressively, while blood BOHB decreased. This exploratory study indicates that breath acetone reliably detects a stimulation of ketogenesis during a short-term fast. It also suggests that LC and HC differentially impact BOHB and acetone production and utilization, and reveals possible limitations to the use of breath acetone as a marker of energy balance.

The Impact of Caloric and Non-Caloric Sweeteners on Food Intake and Brain Responses to Food: A Randomized Crossover Controlled Trial in Healthy Humans

Whether non-nutritive sweetener (NNS) consumption impacts food intake behavior in humans is still unclear. Discrepant sensory and metabolic signals are proposed to mislead brain regulatory centers, in turn promoting maladaptive food choices favoring weight gain. We aimed to assess whether ingestion of sucrose- and NNS-sweetened drinks would differently alter brain responses to food viewing and food intake. Eighteen normal-weight men were studied in a fasted condition and after consumption of a standardized meal accompanied by either a NNS-sweetened (NNS), or a sucrose-sweetened (SUC) drink, or water (WAT). Their brain responses to visual food cues were assessed by means of electroencephalography (EEG) before and 45 min after meal ingestion. Four hours after meal ingestion, spontaneous food intake was monitored during an ad libitum buffet. With WAT, meal intake led to increased neural activity in the dorsal prefrontal cortex and the insula, areas linked to cognitive control and interoception. With SUC, neural activity in the insula increased as well, but decreased in temporal regions linked to food categorization, and remained unchanged in dorsal prefrontal areas. The latter modulations were associated with a significantly lower total energy intake at buffet (mean kcal ± SEM; 791 ± 62) as compared to WAT (942 ± 71) and NNS (917 ± 70). In contrast to WAT and SUC, NNS consumption did not impact activity in the insula, but led to increased neural activity in ventrolateral prefrontal regions linked to the inhibition of reward. Total energy intake at the buffet was not significantly different between WAT and NNS. Our findings highlight the differential impact of caloric and non-caloric sweeteners on subsequent brain responses to visual food cues and energy intake. These variations may reflect an initial stage of adaptation to taste-calorie uncoupling, and could be indicative of longer-term consequences of repeated NNS consumption on food intake behavior.