Impact of Plant-Based Dietary Fibers on Metabolic Homeostasis in High-Fat Diet Mice via Alterations in the Gut Microbiota and Metabolites.

BACKGROUND: The gut microbiota contributes to metabolic disease, and diet shapes the gut microbiota, emphasizing the need to better understand how diet impacts metabolic disease via gut microbiota alterations. Fiber intake is linked with improvements in metabolic homeostasis in rodents and humans, which is associated with changes in the gut microbiota. However, dietary fiber is extremely heterogeneous, and it is imperative to comprehensively analyze the impact of various plant-based fibers on metabolic homeostasis in an identical setting and compare the impact of alterations in the gut microbiota and bacterially derived metabolites from different fiber sources. OBJECTIVES: The objective of this study was to analyze the impact of different plant-based fibers (pectin, ß-glucan, wheat dextrin, resistant starch, and cellulose as a control) on metabolic homeostasis through alterations in the gut microbiota and its metabolites in high-fat diet (HFD)-fed mice. METHODS: HFD-fed mice were supplemented with 5 different fiber types (pectin, ß-glucan, wheat dextrin, resistant starch, or cellulose as a control) at 10% (wt/wt) for 18 wk (n = 12/group), measuring body weight, adiposity, indirect calorimetry, glucose tolerance, and the gut microbiota and metabolites. RESULTS: Only ß-glucan supplementation during HFD-feeding decreased adiposity and body weight gain and improved glucose tolerance compared with HFD-cellulose, whereas all other fibers had no effect. This was associated with increased energy expenditure and locomotor activity in mice compared with HFD-cellulose. All fibers supplemented into an HFD uniquely shifted the intestinal microbiota and cecal short-chain fatty acids; however, only ß-glucan supplementation increased cecal butyrate concentrations. Lastly, all fibers altered the small-intestinal microbiota and portal bile acid composition. CONCLUSIONS: These findings demonstrate that ß-glucan consumption is a promising dietary strategy for metabolic disease, possibly via increased energy expenditure through alterations in the gut microbiota and bacterial metabolites in mice.

Restrictive diets have a beneficial impact on dextran sodium sulfate-induced colitis in male mice.

BACKGROUND: Previously, we assessed the impact of restrictive diets, including caloric restriction (CR), intermittent fasting (IF), or fasting-mimicking diet (FMD), on a healthy gastrointestinal tract. We revealed that each of the diets shows anti-inflammatory outcomes. OBJECTIVE: The current study aimed to verify the diets' applicability in treating colitis. METHODS: We exposed a mouse model with mild chronic dextran sodium sulfate (DSS)-induced colitis to ad libitum control feeding, CR, IF, or FMD. The collected samples were analyzed for markers of inflammation. RESULTS: The diets reduced DSS-triggered increases in spleen weight and myeloperoxidase (MPO) activity. Diet intervention also influenced occludin levels, small intestine morphology, as well as cytokine and inflammatory gene expression, mainly in the mucosa of the proximal colon. The diets did not reverse DSS-enhanced gut permeability and thickening of the colon muscularis externa. Concerning inflammatory gene expression, the impact of DSS and the dietary intervention was limited to the colon as we did not measure major changes in the jejunum mucosa, Peyer's patches, and mesenteric lymph nodes. Further, rather modest changes in the concentration of intestinal bile acids were observed in response to the diets, whereas taurine and its conjugates levels were strongly affected. CONCLUSIONS: Despite the differences in the dietary protocol, the tested diets showed very similar impacts and, therefore, may be interchangeable when aiming to reduce inflammation in the colon. However, FMD showed the most consistent beneficial impact.

Energy and macronutrient restriction regulate bile acid homeostasis.

As we reported previously, caloric restriction (CR) results in an increased concentration of bile acids (BA) in the intestinal mucosa. We now investigated the background of this phenotype, trying to identify nutrition-related factors modulating BA levels. Male mice were submitted to various types of restrictive diets and BA levels and expression of associated factors were measured. We found that BA concentration is increased in the liver of CR mice, which corresponds to reduced expression of the Shp gene and elevated mRNA levels of Cyp27a1, Bal, and Ntcp, as well as CYP7A1 protein and gene expression. Correlation between decreased concentration of BAs in the feces, increased BAs levels in plasma, and elevated gene expression of BAs transporters in the ileum mucosa suggests enhanced BA uptake in the intestine of CR mice. Corresponding to CR upregulation of liver and ileum mucosa, BA concentration was found in animals submitted to other types of prolonged energy-restricting dietary protocols, including intermittent fasting and fasting-mimicking diet. While over-night fasting had negligible impact on BAs levels. Manipulation of macronutrient levels partly affected BA balance. Low-carbohydrate and ketogenic diet increased BAs in the liver but not in the intestine. Carbohydrate restriction stimulates BA synthesis in the liver, but energy restriction is required for the increase in BA levels in the intestine and its uptake.

Ketogenic diets composed of long-chain and medium-chain fatty acids induce cardiac fibrosis in mice.

PURPOSE: Heart diseases are the leading cause of death worldwide. Metabolic interventions via ketogenic diets (KDs) have been used for decades to treat epilepsy, and more recently, also diabetes and obesity, as common comorbidities of heart diseases. However, recent reports linked KDs, based on long-chain triglycerides (LCTs), to cardiac fibrosis and a reduction of heart function in rodents. As intervention using medium-chain triglycerides (MCTs) was recently shown to be beneficial in murine cardiac reperfusion injury, the question arises as to what extent the fatty acid (FA)-composition in a KD alters molecular markers of FA-oxidation (FAO) and modulates cardiac fibrotic outcome. METHODS: The effects of LCT-KD as well as an LCT/MCT mix (8:1 ketogenic ratio) on cardiac tissue integrity and the plasma metabolome were assessed in adult male C57/BL6NRJ mice after eight weeks on the respective diet. RESULTS: Both KDs resulted in increased amount of collagen fibers and cardiac tissue was immunologically indistinguishable between groups. MCT supplementation resulted in i) profound changes in plasma metabolome, ii) reduced hydroxymethylglutaryl-CoA synthase upregulation, and mitofusin 2 downregulation, iii) abrogation of LCT-induced mitochondrial enlargement, and iv) enhanced FAO profile. Contrary to literature, mitochondrial biogenesis was unaffected by KDs. We propose that the observed tissue remodeling is caused by the accumulation of 4-hydroxy-2-nonenal protein adducts, despite an inconspicuous nuclear factor (erythroid-derived 2)-like 2 pathway. CONCLUSION: We conclude that regardless of the generally favorable effects of MCTs, they cannot inhibit 4-hydroxy-2-nonenal adduct formation and fibrotic tissue formation in this setting. Furthermore, we support the burgeoning concern about the effect of KDs on the cardiac safety profile.

Versatile Triad Alliance: Bile Acid, Taurine and Microbiota.

Taurine is the most abundant free amino acid in the body, and is mainly derived from the diet, but can also be produced endogenously from cysteine. It plays multiple essential roles in the body, including development, energy production, osmoregulation, prevention of oxidative stress, and inflammation. Taurine is also crucial as a molecule used to conjugate bile acids (BAs). In the gastrointestinal tract, BAs deconjugation by enteric bacteria results in high levels of unconjugated BAs and free taurine. Depending on conjugation status and other bacterial modifications, BAs constitute a pool of related but highly diverse molecules, each with different properties concerning solubility and toxicity, capacity to activate or inhibit receptors of BAs, and direct and indirect impact on microbiota and the host, whereas free taurine has a largely protective impact on the host, serves as a source of energy for microbiota, regulates bacterial colonization and defends from pathogens. Several remarkable examples of the interaction between taurine and gut microbiota have recently been described. This review will introduce the necessary background information and lay out the latest discoveries in the interaction of the co-reliant triad of BAs, taurine, and microbiota.

A Comparison of the Impact of Restrictive Diets on the Gastrointestinal Tract of Mice.

The rate of gut inflammatory diseases is growing in modern society. Previously, we showed that caloric restriction (CR) shapes gut microbiota composition and diminishes the expression of inflammatory factors along the gastrointestinal (GI) tract. The current project aimed to assess whether prominent dietary restrictive approaches, including intermittent fasting (IF), fasting-mimicking diet (FMD), and ketogenic diet (KD) have a similar effect as CR. We sought to verify which of the restrictive dietary approaches is the most potent and if the molecular pathways responsible for the impact of the diets overlap. We characterized the impact of the diets in the context of several dietary restriction-related parameters, including immune status in the GI tract; microbiota and its metabolites; bile acids (BAs); gut morphology; as well as autophagy-, mitochondria-, and energy restriction-related parameters. The effects of the various diets are very similar, particularly between CR, IF, and FMD. The occurrence of a 50 kDa truncated form of occludin, the composition of the microbiota, and BAs distinguished KD from the other diets. Based on the results, we were able to provide a comprehensive picture of the impact of restrictive diets on the gut, indicating that restrictive protocols aimed at improving gut health may be interchangeable.

Gender, Age, Hunger, and Body Mass Index as Factors Influencing Portion Size Estimation and Ideal Portion Sizes.

Portion sizes of meals have been becoming progressively larger which contributes to the onset of obesity. So far, little research has been done on the influence of body weight on portion size preferences. Therefore, we assessed whether Body Mass Index (BMI), as well as other selected factors, contribute to the estimation of food portions weight and the subjective perception of portion sizes. Through online questionnaires, the participants were asked to estimate the weight of pictured foods in the first study. In the second study, the participants indicated how the depicted varying portion sizes of different meals relate to their actual consumed real-life portion sizes. A total of 725 and 436 individuals were included in the statistical analysis in the first and second study, respectively. BMI and gender had a small effect on the capacity to estimate the weight of foods. The main predictor for portion size choices was the factor gender with men estimating ideal portion sizes as larger than women. Further, age and hunger together with external and restrictive eating behaviors were among the deciding factors for portion size choices. As expected, externally motivated eaters chose bigger portions while restrictive individual smaller ones. Gender- and age-related differences in portion size preferences likely reflect distinct energy requirements. The individuals with a higher BMI do not differ strongly from other BMI groups in their portion-related preferences. Therefore, other factors such as meal frequency, snacking, or a lifestyle, may contribute more to the onset, development, and maintenance of overweight.

Colonic Medium-Chain Fatty Acids Act as a Source of Energy and for Colon Maintenance but Are Not Utilized to Acylate Ghrelin.

The capacity of microbiota to produce medium-chain fatty acids (MCFA) and related consequences for the gastrointestinal (GI) tract have never been reported before. We verified the impact of nutrition-related factors on fatty acid (FAs) production and found that caloric restriction decreased levels of most of MCFAs in the mouse cecum, whereas overnight fasting reduced the levels of acetate and butyrate but increased propionate and laurate. A diet high in soluble fibre boosted the production of short-chain fatty acids (SCFA) and caproate whereas a high-cellulose diet did not have an effect or decreased the levels of some of the FAs. Rectal infusion of caprylate resulted in its rapid metabolism for energy production. Repeated 10-day MCFA infusion impacted epididymal white adipose tissue (eWAT) weight and lipid accumulation. Repeated infusion of caprylate rectally tended to increase the concentration of active ghrelin in mice plasma; however, this increase was not statistically significant. In Caco-2 cells, caprylate increased the expression of Fabp2, Pdk4, Tlr3, and Gpr40 genes as well as counteracted TNFα-triggered downregulation of Pparγ, Occludin, and Zonulin mRNA expression. In conclusion, we show that colonic MCFAs can be rapidly utilized as a source of energy or stored as a lipid supply. Further, locally produced caprylate may impact metabolism and inflammatory parameters in the colon.

Microbial contribution to the caloric restriction-triggered regulation of the intestinal levels of glutathione transferases, taurine, and bile acid.

Recently we showed that caloric restriction (CR) triggers an increase in the levels of free taurine, taurine-conjugated bile acids (BA), and other taurine conjugates in intestinal mucosa while decreasing glutathione (GSH) levels in wild-type male mice. In the current project, we decided to investigate whether the microbiota is involved in the response to CR by depleting gut bacteria. The antibiotics treatment diminished CR-specific increase in the levels of free taurine and its conjugates as well as upregulated expression and activity of GSH transferases (GST) in the intestinal mucosa. Further, it diminished a CR-related increase in BAs levels in the liver, plasma, and intestinal mucosa. Transplant of microbiota from CR mice to ad libitum fed mice triggered CR-like changes in MGST1 expression, levels of taurine and taurine conjugates in the mucosa of the ileum. We show for the first time, that microbiota contributes to the intestinal response to CR-triggered changes in BA, taurine, and GST levels.

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction.

Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR's anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection.

Caloric restriction increases levels of taurine in the intestine and stimulates taurine uptake by conjugation to glutathione.

Our previous study indicated increased levels of taurine-conjugated bile acids (BA) in the intestine content of mice submitted to caloric restriction (CR). In the current project, we found increased levels of free taurine and taurine conjugates, including glutathione (GSH)-taurine, in CR compared to ad libitum fed animals in the mucosa along the intestine but not in the liver. The levels of free GSH were decreased in the intestine of CR compared to ad libitum fed mice. However, the levels of oxidized GSH were not affected and were complemented by the lack of changes in the antioxidative parameters. Glutathione-S transferases (GST) enzymatic activity was increased as was the expression of GST genes along the gastrointestinal tract of CR mice. In the CR intestine, addition of GSH to taurine solution enhanced taurine uptake. Accordingly, the expression of taurine transporter (TauT) was increased in the ileum of CR animals and the levels of free and BA-conjugated taurine were lower in the feces of CR compared to ad libitum fed mice. Fittingly, BA- and GSH-conjugated taurine levels were increased in the plasma of CR mice, however, free taurine remained unaffected. We conclude that CR-triggered production and release of taurine-conjugated BA in the intestine results in increased levels of free taurine what stimulates GST to conjugate and enhance uptake of taurine from the intestine.

Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans.

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.

Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm.

The circadian rhythm plays a chief role in the adaptation of all bodily processes to internal and environmental changes on the daily basis. Next to light/dark phases, feeding patterns constitute the most essential element entraining daily oscillations, and therefore, timely and appropriate restrictive diets have a great capacity to restore the circadian rhythm. One of the restrictive nutritional approaches, caloric restriction (CR) achieves stunning results in extending health span and life span via coordinated changes in multiple biological functions from the molecular, cellular, to the whole-body levels. The main molecular pathways affected by CR include mTOR, insulin signaling, AMPK, and sirtuins. Members of the family of nuclear receptors, the three peroxisome proliferator-activated receptors (PPARs), PPARα, PPARß/δ, and PPARγ take part in the modulation of these pathways. In this non-systematic review, we describe the molecular interconnection between circadian rhythm, CR-associated pathways, and PPARs. Further, we identify a link between circadian rhythm and the outcomes of CR on the whole-body level including oxidative stress, inflammation, and aging. Since PPARs contribute to many changes triggered by CR, we discuss the potential involvement of PPARs in bridging CR and circadian rhythm.

PPARs and Microbiota in Skeletal Muscle Health and Wasting.

Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and fasting. Skeletal muscle wasting occurs in many diseases and during aging. Muscle wasting is often accompanied by chronic low-grade inflammation associated to inter- and intra-muscular fat deposition. During aging, muscle wasting is advanced due to increased movement disorders, as a result of restricted physical exercise, frailty, and the pain associated with arthritis. Muscle atrophy is characterized by increased protein degradation, where the ubiquitin-proteasomal and autophagy-lysosomal pathways, atrogenes, and growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcription factors, which are activated by fatty acids and their derivatives. PPARs regulate genes that are involved in development, metabolism, inflammation, and many cellular processes in different organs. PPARs are also expressed in muscle and exert pleiotropic specialized responses upon activation by their ligands. There are three PPAR isotypes, viz., PPARα, -ß/δ, and -γ. The expression of PPARα is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPARß/δ is expressed more ubiquitously and is the predominant isotype in skeletal muscle. It is involved in energy metabolism, mitochondrial biogenesis, and fiber-type switching. The expression of PPARγ is high in adipocytes, but it is also implicated in lipid deposition in muscle and other organs. Collectively, all three PPAR isotypes have a major impact on muscle homeostasis either directly or indirectly. Furthermore, reciprocal interactions have been found between PPARs and the gut microbiota along the gut-muscle axis in both health and disease. Herein, we review functions of PPARs in skeletal muscle and their interaction with the gut microbiota in the context of muscle wasting.

Peroxisome Proliferator-Activated Receptors and Caloric Restriction-Common Pathways Affecting Metabolism, Health, and Longevity.

Caloric restriction (CR) is a traditional but scientifically verified approach to promoting health and increasing lifespan. CR exerts its effects through multiple molecular pathways that trigger major metabolic adaptations. It influences key nutrient and energy-sensing pathways including mammalian target of rapamycin, Sirtuin 1, AMP-activated protein kinase, and insulin signaling, ultimately resulting in reductions in basic metabolic rate, inflammation, and oxidative stress, as well as increased autophagy and mitochondrial efficiency. CR shares multiple overlapping pathways with peroxisome proliferator-activated receptors (PPARs), particularly in energy metabolism and inflammation. Consequently, several lines of evidence suggest that PPARs might be indispensable for beneficial outcomes related to CR. In this review, we present the available evidence for the interconnection between CR and PPARs, highlighting their shared pathways and analyzing their interaction. We also discuss the possible contributions of PPARs to the effects of CR on whole organism outcomes.

Visual stimulation with food pictures in the regulation of hunger hormones and nutrient deposition, a potential contributor to the obesity crisis.

Food cues affect hunger and nutritional choices. Omnipresent stimulation with palatable food contributes to the epidemics of obesity. The objective of the study was to investigate the impact of food cues on appetite-related hormones and to assess the functionality of the secreted hormones on macronutrient uptake in healthy subjects. Additionally, we aimed at verifying differences in the response of total and active ghrelin to stimulation with food pictures and to a meal followed by the stimulation. We were also interested in the identification of factors contributing to response to food cues. We recruited healthy, non-obese participants for two independent cross-over studies. During the first study, the subjects were presented random non-food pictures on the first day and pictures of foods on the second day of the study. Throughout the second study, following the picture session, the participants were additionally asked to drink a milkshake. Concentrations of blood glucose, triglycerides and hunger-related hormones were measured. The results showed that concentrations of several hormones measured in the blood are interdependent. In the case of ghrelin and gastric inhibitory peptide (GIP) as well as ghrelin and glucagon-like peptide-1 (GLP-1), this co-occurrence relies on the visual cues. Regulation of total ghrelin concentration following food stimulation is highly individual and responders showed upregulated total ghrelin, while the concentration of active ghrelin decreases following a meal. Protein content and colour intensity of food pictures reversely correlated with participants' rating of the pictures. We conclude that observation of food pictures influences the concentration of several appetite-related hormones. The close link of visual clues to physiological responses is likely of clinical relevance. Additionally, the protein content of displayed foods and green colour intensity in pictures may serve as a predictor of subjective attractiveness of the presented meal.

Enteric Microbiota⁻Gut⁻Brain Axis from the Perspective of Nuclear Receptors.

Nuclear receptors (NRs) play a key role in regulating virtually all body functions, thus maintaining a healthy operating body with all its complex systems. Recently, gut microbiota emerged as major factor contributing to the health of the whole organism. Enteric bacteria have multiple ways to influence their host and several of them involve communication with the brain. Mounting evidence of cooperation between gut flora and NRs is already available. However, the full potential of the microbiota interconnection with NRs remains to be uncovered. Herewith, we present the current state of knowledge on the multifaceted roles of NRs in the enteric microbiota⁻gut⁻brain axis.

Complementary intestinal mucosa and microbiota responses to caloric restriction.

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR.

The OEA effect on food intake is independent from the presence of PPARα in the intestine and the nodose ganglion, while the impact of OEA on energy expenditure requires the presence of PPARα in mice.

BACKGROUND: Oleoylethanolamide (OEA) is an endocannabinoid that controls food intake, energy expenditure and locomotor activity. Its anorexigenic effect appears to be mediated by PPARα, but the tissue where the presence of this receptor is required for OEA to inhibit feeding is unknown as yet. Previous studies point to a possible role of proximal enterocytes and neurons of the nodose ganglion. MATERIALS AND METHODS: Acute intraperitoneal OEA effects on food intake, energy expenditure, respiratory exchange ratio (RER) and locomotor activity were studied in control mice (PPARα-loxP) and intestinal (Villin-Cre;PPARα-loxP) or nodose ganglion (Phox2B-Cre;PPARα-loxP) specific PPARα knockout mice placed in calorimetric cages. RESULTS: OEA administration to both intestinal and nodose ganglion PPARα knockout mice decreased food intake, RER (leading to increased lipid oxidation) and locomotor activity as in control mice. However, while OEA injection acutely decreased energy expenditure in controls, this effect was not observed in mice devoid of PPARα in the intestine. CONCLUSION: These results indicate that the OEA effect on food intake is independent from the presence of PPARα in the intestine and the nodose ganglion, while the impact of OEA on energy expenditure requires the presence of PPARα in the intestine.