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The ingestion of low or high lipid diets enriched with fructo-oligosaccharide (FOS) affects energy homeostasis. Ingesting protein diets also induces a depression of energy intake and decreases body weight. The goal of this study was to investigate the ability of FOS, combined or not with a high level of protein (P), to affect energy intake and body composition when included in diets containing different levels of lipids (L). We performed two studies of similar design over a period of 5weeks. During the first experiment (exp1), after a 3-week period of adaptation to a normal protein-low fat diet, the rats received one of the following four diets for 5weeks (6 rats per group): (i) normal protein (14% P/E (Energy) low fat (10% L/E) diet, (ii) normal protein, low fat diet supplemented with 10% FOS, (iii) high protein (55%P/E) low fat diet, and (iv) high protein, low fat diet supplemented with 10% FOS. In a second experiment (exp2) after the 3-week period of adaptation to a normal protein-high fat diet, the rats received one of the following 4 diets for 5weeks (6 rats per group): (i) normal protein, high fat diet (35% of fat), (ii) normal protein, high fat diet supplemented with 10% FOS, (iii) high protein high fat diet and (iv) high protein high fat diet supplemented with 10% FOS. In low-fat fed rats, FOS did not affect lean body mass (LBM) and fat mass but the protein level reduced fat mass and tended to reduce adiposity. In high-fat fed rats, FOS did not affect LBM but reduced fat mass and adiposity. No additive or antagonistic effects between FOS and the protein level were observed. FOS reduced energy intake in low-fat fed rats, did not affect energy intake in normal-protein high-fat fed rats but surprisingly, and significantly, increased energy intake in high-protein high-fat fed rats. The results thus showed that FOS added to a high-fat diet reduced body fat and body adiposity., (Published by Elsevier Inc.)

Human consumption of obesogenic diets and soft drinks, sweetened with different molecules, is increasing worldwide, and increases the risk of metabolic diseases. We hypothesized that the chronic consumption of caloric (sucrose, high-fructose corn syrup (HFCS), maltodextrin) and non-caloric (sucralose) solutions under 2-hour intermittent access, alongside the consumption of a high-fat high-sucrose diet, would result in differential obesity-associated metabolic abnormalities in mice. Male C57BL/6 mice had ad libitum access to an HFHS diet and to water (water control group). In addition, some mice had access, 2h/day, 5days/week (randomly chosen) for 12weeks, to different solutions: i) a sucrose solution (2.1kJ/ml), ii) an HFCS solution (2.1kJ/ml), iii) a maltodextrin solution (2.1kJ/ml) and a sucralose solution (60mM) (n=15/group). Despite no changes in total caloric intake, 2h-intermittent access to the sucrose, HFCS or maltodextrin solutions led to increased body weight and accumulation of lipids in the liver when compared to the group consuming water only. The HFCS and sucrose solutions induced a higher fat mass in various fat depots, glucose intolerance, increased glucose oxidation at the expense of lipid oxidation, and a lower hypothalamic expression of NPY in the fasted state. HFCS also reduced proopiomelanocortin expression in the hypothalamus. 2h-intermittent access to sucralose did not result in significant changes in body composition, but caused a stronger expression of CART in the hypothalamus. Finally, sucrose intake showed a trend to increase the expression of various receptors in the nucleus accumbens, linked to dopamine, opioid and endocannabinoid signaling. In conclusion, 2h-intermittent access to caloric solutions (especially those sweetened with sucrose and HFCS), but not sucralose, resulted in adverse metabolic consequences in high-fat high-sucrose-fed mice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To prevent the development of adiposity-associated metabolic diseases, early biomarkers are needed. Such markers could bring insight to understand the complexity of susceptibility to obesity. Urine and plasma metabolomics fingerprints have been successfully associated with metabolic dysfunctions. Fat resistance (FR) was found to be associated with higher urinary levels of acylglycines and leucine. However, no differences were observed before the diet switch. In this context, we aimed at characterizing metabolic signatures predictive of resistance or sensitivity to fat in the C57Bl6/J mouse model. Urinary metabolic profiles of FR (n=15) and fat sensitivity (FS) mice (n=14) were performed on liquid chromatography-mass spectrometry. Urinary and plasma metabolic profiles were first collected at baseline (during low-fat diet), then after 10weeks of high-fat (HF) feeding. Mice were sorted a posteriori into FS and FR based on their final adiposity. After HF feeding for 10weeks, FS mice tended to have lower plasma levels of β-hydroxybutyrate than FR ones. Urinary metabolic profiles showed that baseline levels of octanoylglycine, leucine and valine were significantly lower in FS mice. Moreover, expressions in the adipose tissue of Baat and Glyat mRNA were lower in FS than in FR mice. In muscle, mRNA encoding CaD and UbE2b tended to be lower in FS mice than in FR mice (P=.056 and P=.071, respectively). The data show that lower levels of urinary octanoylglycine, leucine and valine are potential predictive biomarkers of FS and could be related to a lower stimulation in adipose acyl-coenzyme A conjugation to glycine and to muscle protein breakdown., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Consumption of sugar-sweetened beverages is associated with overweight and obesity. In this study, we hypothesized that obesity-prone (OP) mice fed a high-fat high-sucrose diet (HFHS) are more sensitive to consumption of sucrose-sweetened water (SSW) than obesity-resistant (OR) mice. After 3weeks of ad libitum access to the HFHS diet (7.5h/day), 180 male mice were classified as either OP (upper quartile of body weight gain, 5.2±0.1g, n=45) or OR (lower quartile, 3.2±0.1g, n=45). OP and OR mice were subsequently divided into 3 subgroups that had access to HFHS (7.5h/day) for 16weeks, supplemented with: i) water (OP/water and OR/water); ii) water and SSW (12.6% w/v), available for 2h/day randomly when access to HFHS was available and for 5 randomly-chosen days/week (OP/SSW and OR/SSW); or iii) water and SSW for 8weeks, then only water for 8weeks (OP/SSW-water and OR/SSW-water). OR/SSW mice decreased their food intake compared to OR/water mice, while OP/SSW mice exhibited an increase in food and total energy intake compared to OP/water mice. OP/SSW mice also gained more body weight and fat mass than OP/water mice, showed an increase in liver triglycerides and developed insulin resistance. These effects were fully reversed in OP/SSW-water mice. In the gut, OR/SSW mice, but not OP/SSW mice, had an increase GLP-1 and CCK response to a liquid meal compared to mice drinking only water. OP/SSW mice had a decreased expression of melanocortin receptor 4 in the hypothalamus and increased expression of delta opioid receptor in the nucleus accumbens compared to OP/water mice when fasted that could explain the hyperphagia in these mice. When access to the sucrose solution was removed for 8weeks, OP mice had increased dopaminergic and opioidergic response to a sucrose solution. Thus, intermittent access to a sucrose solution in mice fed a HFHS diet induces changes in the gut and brain signaling, leading to increased energy intake and adverse metabolic consequences only in mice prone to HFHS-induced obesity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Fermentable dietary fibre such as fructo-oligosaccharide and viscous dietary fibers such as guar gum and alginate affect energy homeostasis. The goal of this study was to compare the impact of long term intake of these three dietary fibers on food intake, meal pattern, body weight and fat accumulation in mice. Over a period of 3weeks, the mice were fed daily with a preload containing 32mg of fructo-oligosaccharide or alginate or 13mg of guar gum. Food intake and body weight were monitored weekly, while meal patterns, adiposity and the expression of hypothalamic neuropeptide genes were evaluated at the end of the study period. The 3 dietary fibers produced a similar decrease in total daily food intake (14 to 22%) at the end of the first week, and this effect disappeared over time. The 3 dietary fibers induced a slight variation in satiation parameters. Body weight and expression of hypothalamic neuropeptide genes were not affected by any of the treatment. Preload of fructo-oligosaccharide and guar gum induced a similar and substantial decrease in the development of adiposity (17% and 14%, respectively), while alginate had no effect. Our results demonstrate mainly that the inhibitory effect of dietary fiber on food intake is lost over time, and that guar gum limits fat storage., (Copyright © 2015. Published by Elsevier Inc.)

Intake of sodas has been shown to increase energy intake and to contribute to obesity in humans and in animal models, although the magnitude and importance of these effects are still debated. Moreover, intake of sugar sweetened beverages is often associated with high-fat food consumption in humans. We studied two different accesses to a sucrose-sweetened water (SSW, 12.3%, a concentration similar to that usually found in sugar sweetened beverages) in C57BL/6 mice fed a normal-fat (NF) or a high-fat (HF) diet in a scheduled access (7.5h). NF-fed and HF-fed mice received during 5weeks access to water, to SSW continuously for 7.5h (SSW), or to water plus SSW for 2h (randomly-chosen time slot for only 5 random days/week) (SSW-2h). Mouse preference for SSW was greater in HF-fed mice than NF-fed mice. Continuous SSW access induced weight gain whatever the diet and led to greater caloric intake than mice drinking water in NF-fed mice and in the first three weeks in HF-fed mice. In HF-fed mice, 2h-intermittent access to SSW induced a greater body weight gain than mice drinking water, and led to hyperphagia on the HF diet when SSW was accessible compared to days without SSW 2h-access (leading to greater overall caloric intake), possibly through inactivation of the anorexigenic neuropeptide POMC in the hypothalamus. This was not observed in NF-fed mice, but 2h-intermittent access to SSW stimulated the expression of dopamine, opioid and endocannabinoid receptors in the nucleus accumbens compared to water-access. In conclusion, in mice, a sucrose solution provided 2h-intermittently and a high-fat diet have combined effects on peripheral and central homeostatic systems involved in food intake regulation, a finding which has significant implications for human obesity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

It is well known that intake of dietary fiber (DF) potently decreases food intake and feelings of hunger and/or promotes satiety ratings. However, the mechanisms explaining these effects are not well characterized. This work was performed to determine which of satiation and/or satiety mechanisms provoke the decrease of food intake induced by DF in mice. We tested in an intra-group protocol a low-viscosity (LV, fructo-oligosaccharide), a viscous (VP, guar gum) and a high-viscosity (HV, mixture of guar gum and fructo-oligosaccharide) preload. These were given to mice by intra-gastric gavage. It appeared that viscous preloads such as VP and HV reduced the daily energy intake by 14% and 21% respectively. The strong effect of HV was mainly due to a large decrease of meal size (by 57%) and meal duration (by 65%) with no effect on ingestion rate during the first 30 min after administration. Therefore, the DF-induced decrease of energy intake was due to a satiation mechanism. This is further supported by a 3-fold increased sensitization of neurons in the nucleus of the solitary tract as observed by c-Fos protein immunolabelling. No compensation of food intake was observed during the rest of the day, a phenomenon that may be explained by the fact that metabolic rate remained high despite the lower food intake. We have also shown that the DF-induced inhibition of food intake was not paired with a conditioned taste aversion. To conclude, this work demonstrates that DF inhibits food intake by increasing satiation during ~1h after administration., (Copyright © 2012 Elsevier Inc. All rights reserved.)

High-protein (HP) milk formulas are routinely used in infants born with a low birth weight (LBW) to enhance growth and ensure a better verbal IQ development. Indirect evidence points to a link between an HP intake during early life and the prevalence of obesity in later life. We hypothesized that HP milk supplementation to LBW pups during early postnatal life would impact hypothalamic appetite neuronal pathways development with consequences, at adulthood, on energy homeostasis regulation. Rat pups born with a LBW were equipped with gastrostomy tubes on the fifth day of life. They received a milk formula with either normal protein (NP, 8.7 g protein/dl) or high protein content (HP; 13.0 g protein/dl) and were subsequently weaned to a standard, solid diet at postnatal day 21. Rats that had been fed HP content milk gained more weight at adulthood associated with an increase of plasma insulin, leptin and triglycerides concentrations compared to NP rats. Screening performed on hypothalamus in development from the two groups of rats identified higher gene expression for cell proliferation and neurotrophin markers in HP rats. Despite these molecular differences, appetite neuronal projections emanating from the arcuate nucleus did not differ between the groups. Concerning feeding behavior at adulthood, rats that had been fed HP or NP milk exhibited differences in the satiety period, resting postprandial duration and nocturnal meal pattern. The consequences of HP milk supplementation after LBW will be discussed in regard to neural development and metabolic anomalies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study aimed to compare energy balance, metabolic profiles and body composition between two inbred strains of rats (F344 and Lou) submitted to a self-selecting macronutrient. During the 3 weeks of experiment, the two strains did not differ significantly for their total energy intake; males: F344 = 5875.4 +/- 171.4 kJ, Lou = 5619.2 +/- 349.4 kJ; and females: F344 = 4058.8 +/- 118.7 kJ, Lou = 3864.4+/-166.4 kJ. However, F344 rats showed a higher weight gain, and percentage of total fat tissue, together with a lower percentage of carcass weight than Lou rats regardless of sex. The percentages of each macronutrient revealed a lower preference of protein for F344 males and the opposite in females for CHO. The thermogenic activity measured in interscapular brown adipose tissue was lower in Fischer than in Lou while the reverse was observed for leptinemia and insulinemia. These results indicate that the mechanism responsible for the regulation of body composition observed in Lou rats takes place very early in life and attest the interest in this strain for studying the features of resistance to obesity.

The factors involved in the depression of food intake produced by a high-protein diet are still poorly understood. The aim of this study was to assess the role of several preingestive or preabsorptive factors likely to influence food intake when rats were fed ad libitum. Food intake was measured after modifying the composition of the high-protein diet, i.e., the type of proteins, or carbohydrates. Moreover, correlations between high-protein diet intake and the quantity of fluid ingested or stomach volume were studied. By varying the carbohydrate composition (sucrose/cornstarch) and the protein source (soy or gluten or total milk protein) of high-protein diets, we modified the orosensory properties of these diets. However, no differences in food intake were observed between these groups of rats during the transition phase or after adaptation, except during the first day of soy- or gluten-based diets when the depression of food intake was intensified. The depression of high-protein diet intake was neither the consequence of any delay necessary to increase the fluid intake induced by eating a high-protein diet nor due to a marked increase in stomach volume, which might explain enhanced satiety and decreased food intake through the activation of vagal afferent fibers. Our experiments do not indicate a preponderant role for oropharyngeal or preabsorptive factors in the depression of food intake induced by a high-protein diet.

N-acetyl-muramyl-L-alanine-D-isoglutamine or muramyl dipeptide (MDP) is the minimally active subunit of bacterial peptidoglycan. During a systemic infection, the involvement of MDP has been demonstrated in food intake depression by the macrophage hydrolysis of Gram-positive bacteria. Under normal conditions, mammals are constantly exposed to the release of endogenous MDP from degraded gut flora and that of exogenous MDP from the diet. However, MDP digestion and absorption in the gastrointestinal tract are not fully understood, and their physiological significance needs to be clarified. After gavage (1.5 mg/kg), very low levels of MDP were found in the systemic circulation of rats and feeding patterns were not altered. In contrast, after the intraperitoneal injection of a similar dose, a depression in food intake was observed. The rats reduced their meal frequency and constant feeding rate, showing signs of satiety. The behavioral satiety sequence (BSS) was modified by behavioral changes, similar to those which appear during sickness, such as an increase in resting and a reduction in grooming. Our data suggest that the hypophagic effect of MDP may result from satiety and sickness behavior.

In order to determine the respective roles of conditioned food aversion, satiety and palatability, we studied behavioral responses to a 50% total milk protein diet, compared with those to a normal protein diet containing 14% total milk protein. Different paradigms were employed, including meal pattern analysis, two-choice testing, flavor testing, a behavioral satiety sequence (BSS) and taste reactivity. Our experiments showed that only behavioral and food intake parameters were disturbed during the first day when an animal ate the high-protein (P50) diet, and that most parameters returned to baseline values as soon as the second day of P50. Rats adapted to P50 did not acquire a conditioned taste aversion (CTA) but exhibited satiety, and a normal BSS. The initial reduction in high-protein diet intake appeared to result from the lower palatability of the food combined with the satiety effect of the high-protein diet and the delay required for metabolic adaptation to the higher protein level.

The aim of this work was to study the evolution of rat food choice in relation to their age and metabolic parameters. Eighty Wistar rats were studied from birth to 13 weeks of age. At weaning, six litters were fed on a macronutrient self-selecting diet and four on a standard diet. In self-selecting males, protein intake was maximal at Week 7 of age and then plateaued (Week 13), whereas in females, protein consumption peaked at Week 7 and then steadily decreased. Females showed a strong and early preference for fat, which increased continuously with age. Males and females ingested their total energy intake during the dark period (respectively, 79% and 70%). Simple meals (composed of one item) were mainly ingested during the light phase, while mixed meals (at least two items) were ingested during the night. In males, most mixed meals began with carbohydrate bouts and finished with proteins, while in females no particular choice was observed at the beginning of meals, but most of them ended with protein bouts. Body weights of either male and female self-selecting or control fed rats were not significantly different at the end of the experiment. Differences between dietary groups in body fat mass were not observed with the exception of higher subcutaneous fat found in self-selecting rats. Moreover, insulinemia was lower in both male and female self-selecting rats. The high-protein, high-fat diet chosen by the self-selecting rats could be linked to a prevention of the age-related insulin resistance.

The purpose of this study was to characterize further the effects of loads of protein versus carbohydrate on subsequent food intake in rats. We used an intraoral cannula to deliver isoenergetic isovolumic loads, in a tightly controlled time frame allowing for both metabolic responses and orosensory components of the load. Our results showed that the gluten load (GLT-100%) induced a greater depression in food intake than an isocaloric wheat starch load (GLT-0%). The types of protein used in the load (total milk protein vs. GLT) did not seem to influence their appetite-suppressive effect. There was a dose-dependent effect of the satiating effects of the protein loads, the GLT-100% load being more effective than either the GLT-35% or GLT-50% loads. Pattern analysis of the meal following the load suggested that animals were more satiated by protein, at least when loads contained 35% or 50% of protein, than by carbohydrate. At least 1 day was necessary before we saw a significant decrease in the energy intake following the protein loads. Thus, the animals had to learn the postingestive effects of the loads before the response stabilized. Taken together, the present results confirm that protein has a greater satiating effect than carbohydrate and extend these results by revealing that the larger the proportion of protein in the food, the larger the satiating effect, and that the quality of protein does not seem to play a significant role.