An inter-organ neural circuit for appetite suppression.

Glucagon-like peptide-1 (GLP-1) is a signal peptide released from enteroendocrine cells of the lower intestine. GLP-1 exerts anorectic and antimotility actions that protect the body against nutrient malabsorption. However, little is known about how intestinal GLP-1 affects distant organs despite rapid enzymatic inactivation. We show that intestinal GLP-1 inhibits gastric emptying and eating via intestinofugal neurons, a subclass of myenteric neurons that project to abdominal sympathetic ganglia. Remarkably, cell-specific ablation of intestinofugal neurons eliminated intestinal GLP-1 effects, and their chemical activation functioned as a GLP-1 mimetic. GLP-1 sensing by intestinofugal neurons then engaged a sympatho-gastro-spinal-reticular-hypothalamic pathway that links abnormal stomach distension to craniofacial programs for food rejection. Within this pathway, cell-specific activation of discrete neuronal populations caused systemic GLP-1-like effects. These molecularly identified, delimited enteric circuits may be targeted to ameliorate the abdominal bloating and loss of appetite typical of gastric motility disorders.

Amelioration impact of gut-brain communication on obesity control by regulating gut microbiota composition through the ingestion of animal-plant-derived peptides and dietary fiber: can food reward effect as a hidden regulator?

Various roles of intestinal flora in the gut-brain axis response pathway have received enormous attention because of their unique position in intestinal flora-derived metabolites regulating hormones, inducing appetite, and modulating energy metabolism. Reward pathways in the brain play a crucial role in gut-brain communications, but the mechanisms have not been methodically understood. This review outlined the mechanisms by which leptin, ghrelin, and insulin are influenced by intestinal flora-derived metabolites to regulate appetite and body weight, focused on the significance of the paraventricular nucleus and ventromedial prefrontal cortex in food reward. The vagus nerve and mitochondria are essential pathways of the intestinal flora involved in the modulation of neurotransmitters, neural signaling, and neurotransmission in gut-brain communications. The dynamic response to nutrient intake and changes in the characteristics of feeding activity requires the participation of the vagus nerve to transmit messages to be completed. SCFAs, Bas, BCAAs, and induced hormones mediate the sensory information and reward signaling of the host in the complex regulatory mechanism of food selection, and the composition of the intestinal flora significantly impacts this process. Food reward in the process of obesity based on gut-brain communications expands new ideas for the prevention and treatment of obesity.

Gut peptide regulation of food intake - evidence for the modulation of hedonic feeding.

The number of people living with obesity has tripled worldwide since 1975 with serious implications for public health, as obesity is linked to a significantly higher chance of early death from associated comorbidities (metabolic syndrome, type 2 diabetes, cardiovascular disease and cancer). As obesity is a consequence of food intake exceeding the demands of energy expenditure, efforts are being made to better understand the homeostatic and hedonic mechanisms governing food intake. Gastrointestinal peptides are secreted from enteroendocrine cells in response to nutrient and energy intake, and modulate food intake either via afferent nerves, including the vagus nerve, or directly within the central nervous system, predominantly gaining access at circumventricular organs. Enteroendocrine hormones modulate homeostatic control centres at hypothalamic nuclei and the dorso-vagal complex. Additional roles of these peptides in modulating hedonic food intake and/or preference via the neural systems of reward are starting to be elucidated, with both peripheral and central peptide sources potentially contributing to central receptor activation. Pharmacological interventions and gastric bypass surgery for the treatment of type 2 diabetes and obesity elevate enteroendocrine hormone levels and also alter food preference. Hence, understanding of the hedonic mechanisms mediated by gut peptide action could advance development of potential therapeutic strategies for the treatment of obesity and its comorbidities.

Administration of Exendin-4 but not CCK alters lick responses and trial initiation to sucrose and intralipid during brief-access tests.

Administration of cholecystokinin (CCK) or the glucagon-like peptide 1 (GLP-1) receptor agonist Exendin-4 (Ex-4) reduces food intake. Findings in the literature suggest CCK reduces intake primarily as a satiety signal whereas GLP-1 may play a role in both satiety and reward-related feeding signals. Compounds that humans describe as âsweetâ and âfattyâ are palatable yet are signaled via separate transduction pathways. Here, unconditioned lick responses to sucrose and intralipid were measured in a brief-access lick procedure in food-restricted male rats in response to i.p. administration of Ex-4 (3 h before test), CCK (30 min before test), or a combination of both. The current experimental design measures lick responses to water and varying concentrations of both sucrose (0.03, 0.1, and 0.5 M) and intralipid (0.2%, 2%, and 20%) during 10-s trials across a 30-min single test session. This design minimized postingestive influences. Compared with saline-injected controls, CCK (1.0, 3.0, or 6.0 µg/kg) did not change lick responses to sucrose or intralipid. Number of trials initiated and lick responses to both sucrose and intralipid were reduced in rats injected with 3.0 µg/kg, but not 1.0 µg/kg Ex-4. The supplement of CCK did not alter lick responses or trials initiated compared with Ex-4 administration alone. These findings support a role for GLP-1 but not CCK in the oral responsiveness to palatable stimuli. Furthermore, Ex-4-induced reductions were observed for both sucrose and intralipid, compounds representing âsweetâ and âfat,â respectively.

Hypothalamic regulation of energy homoeostasis when consuming diets of different energy concentrations: comparison between Tibetan and Small-tailed Han sheep.

Seasonal energy intake of Tibetan sheep on the harsh Qinghai-Tibetan Plateau (QTP) fluctuates greatly and is often well below maintenance requirements. The aim of this study was to gain insight into how the hypothalamus regulates energy homoeostasis in Tibetan sheep. We compared Tibetan and Small-tailed Han sheep (n 24 of each breed), which were each allocated randomly into four groups and offered one of four diets that differed in digestible energy densities: 8·21, 9·33, 10·45 and 11·57 MJ/kg DM. Sheep were weighed every 2 weeks, and it was assumed that the change in body weight (BW) reflected the change in energy balance. The arcuate nucleus of the hypothalamus in Tibetan sheep had greater protein expressions of neuropeptide Y (NPY) and agouti-related peptide (AgRP) when in negative energy balance, but lesser protein expressions of proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) when in positive energy balance than Small-tailed Han sheep. As a result, Tibetan sheep had a lesser BW loss when in negative energy balance and stored more energy and gained more BW when in positive energy balance than Small-tailed Han sheep with the same dietary intake. Moreover, in the hypothalamic adenosine monophosphate-activated protein kinase (AMPK) regulation pathway, Tibetan sheep had greater adenosine monophosphate-activated protein kinase-α 2 protein expression than Small-tailed Han sheep, which supported the premise of a better ability to regulate energy homoeostasis and better growth performance. These differences in the hypothalamic NPY/AgRP, POMC/CART and AMPK pathways between breeds conferred an advantage to the Tibetan over Small-tailed Han sheep to cope with low energy intake on the harsh QTP.

Postprandial glycine as a biomarker of satiety: A dose-rising randomised control trial of whey protein in overweight women.

This study aimed to identify biomarkers of appetite response, modelled using a dose-rising whey protein preload intervention. Female participants (n = 24) with body mass index (BMI) between 23 and 40 kg/m2 consumed preload beverages (0 g protein water control, WC; 12.5 g low-dose protein, LP; or 50.0 g high-dose protein, HP) after an overnight fast, in a randomised cross over design. Repeated venous blood samples were collected to measure plasma biomarkers of appetite response, including glucose, glucoregulatory peptides, gut peptides, and amino acids (AAs). Appetite was assessed using Visual Analogue Scales (VAS) and ad libitum energy intake (EI). Dose-rising protein beverage significantly changed the postprandial trajectory of almost all biomarkers (treatment*time, p < 0.05), but did not suppress postprandial appetite (treatment*time, p > 0.05) or EI (ANOVA, p = 0.799). Circulating glycine had the strongest association with appetite response. Higher area under the curve (AUC0-240) glycine was associated with lower EI (p = 0.026, trend). Furthermore, circulating glycine was associated with decreased Hunger in all treatment groups, whereas the associations of glucose, alanine and amylin with appetite were dependent on treatment groups. Multivariate models, incorporating multiple biomarkers, improved the estimation of appetite response (marginal R2, range: 0.13-0.43). In conclusion, whilst glycine, both alone and within a multivariate model, can estimate appetite response to both water and whey protein beverage consumption, a large proportion of variance in appetite response remains unexplained. Most biomarkers, when assessed in isolation, are poor predictors of appetite response, and likely of utility only in combination with VAS and EI.

New Insights in the Control of Fat Homeostasis: The Role of Neurotensin.

Neurotensin (NT) is a small peptide with pleiotropic functions, exerting its primary actions by controlling food intake and energy balance. The first evidence of an involvement of NT in metabolism came from studies on the central nervous system and brain circuits, where NT acts as a neurotransmitter, producing different effects in relation to the specific region involved. Moreover, newer interesting chapters on peripheral NT and metabolism have emerged since the first studies on the NT-mediated regulation of gut lipid absorption and fat homeostasis. Intriguingly, NT enhances fat absorption from the gut lumen in the presence of food with a high fat content, and this action may explain the strong association between high circulating levels of pro-NT, the NT stable precursor, and the increased incidence of metabolic disorders, cardiovascular diseases, and cancer observed in large population studies. This review aims to provide a synthetic overview of the main regulatory effects of NT on several biological pathways, particularly those involving energy balance, and will focus on new evidence on the role of NT in controlling fat homeostasis, thus influencing the risk of unfavorable cardio-metabolic outcomes and overall mortality in humans.

Neurohormonal Changes in the Gut-Brain Axis and Underlying Neuroendocrine Mechanisms following Bariatric Surgery.

Obesity is a complex, multifactorial disease that is a major public health issue worldwide. Currently approved anti-obesity medications and lifestyle interventions lack the efficacy and durability needed to combat obesity, especially in individuals with more severe forms or coexisting metabolic disorders, such as poorly controlled type 2 diabetes. Bariatric surgery is considered an effective therapeutic modality with sustained weight loss and metabolic benefits. Numerous genetic and environmental factors have been associated with the pathogenesis of obesity, while cumulative evidence has highlighted the gut-brain axis as a complex bidirectional communication axis that plays a crucial role in energy homeostasis. This has led to increased research on the roles of neuroendocrine signaling pathways and various gastrointestinal peptides as key mediators of the beneficial effects following weight-loss surgery. The accumulate evidence suggests that the development of gut-peptide-based agents can mimic the effects of bariatric surgery and thus is a highly promising treatment strategy that could be explored in future research. This article aims to elucidate the potential underlying neuroendocrine mechanisms of the gut-brain axis and comprehensively review the observed changes of gut hormones associated with bariatric surgery. Moreover, the emerging role of post-bariatric gut microbiota modulation is briefly discussed.

Spatiotemporal organization of enteroendocrine peptide expression in Drosophila.

The digestion of food and absorption of nutrients occurs in the gut. The nutritional value of food and its nutrients is detected by enteroendocrine cells, and peptide hormones produced by the enteroendocrine cells are thought to be involved in metabolic homeostasis, but the specific mechanisms are still elusive. The enteroendocrine cells are scattered over the entire gastrointestinal tract and can be classified according to the hormones they produce. We followed the changes in combinatorial expression of regulatory peptides in the enteroendocrine cells during metamorphosis from the larva to the adult fruit fly, and re-confirmed the diverse composition of enteroendocrine cell populations. Drosophila enteroendocrine cells appear to differentially regulate peptide expression spatially and temporally depending on midgut region and developmental stage. In the late pupa, Notch activity is known to determine which peptides are expressed in mature enteroendocrine cells of the posterior midgut, and we found that the loss of Notch activity in the anterior midgut results in classes of enteroendocrine cells distinct from the posterior midgut. These results suggest that enteroendocrine cells that populate the fly midgut can differentiate into distinct subtypes that express different combinations of peptides, which likely leads to functional variety depending on specific needs.

Enteroendocrine Regulation of Nutrient Absorption.

Enteroendocrine cells (EECs) in the intestine regulate many aspects of whole-body physiology and metabolism. EECs sense luminal and circulating nutrients and respond by secreting hormones that act on multiple organs and organ systems, such as the brain, gallbladder, and pancreas, to control satiety, digestion, and glucose homeostasis. In addition, EECs act locally, on enteric neurons, endothelial cells, and the gastrointestinal epithelium, to facilitate digestion and absorption of nutrients. Many recent reports raise the possibility that EECs and the enteric nervous system may coordinate to regulate gastrointestinal functions. Loss of all EECs results in chronic malabsorptive diarrhea, placing EECs in a central role regulating nutrient absorption in the gut. Because there is increasing evidence that EECs can directly modulate the efficiency of nutrient absorption, it is possible that EECs are master regulators of a feed-forward loop connecting appetite, digestion, metabolism, and abnormally augmented nutrient absorption that perpetuates metabolic disease. This review focuses on the roles that specific EEC hormones play on glucose, peptide, and lipid absorption within the intestine.

Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism.

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.

The Association Between Kidney Disease and Diabetes Remission in Bariatric Surgery Patients With Type 2 Diabetes.

RATIONALE & OBJECTIVE: The association between bariatric surgery, type 2 diabetes, and chronic kidney disease (CKD) is poorly understood. We studied whether remission of type 2 diabetes induced by bariatric surgery influences markers of kidney disease, if CKD is associated with remission of diabetes after bariatric surgery, and if baseline levels of gut hormones and peptides modify these associations. STUDY DESIGN: Prospective observational study. STUDY PARTICIPANTS: 737 bariatric surgery patients with type 2 diabetes who participated in a multicenter cohort study for up to 5 years. PREDICTORS: Demographics, blood pressure, medications, type of bariatric surgery, anthropometrics, markers of kidney disease, and circulating levels of gut hormones and peptides. OUTCOMES: Estimated glomerular filtration rate (eGFR), urinary albumin excretion, prognostic risk for CKD, and remission of diabetes. ANALYTICAL APPROACH: Linear mixed models for eGFR; generalized linear mixed models with logit link for albuminuria, prognostic risk for CKD, and diabetes remission. RESULTS: Remission of diabetes at 5 years post-bariatric surgery was not independently associated with eGFR but was associated with lower risk for moderate/severe increase in albuminuria (risk ratio, 0.66; 95% CI, 0.48-0.90) and stabilization in prognostic risk for CKD. These findings were modified by baseline ghrelin level. Lower preoperative eGFR and greater prognostic risk for CKD were independently associated with reduced likelihood of diabetes remission. The association with preoperative GFR was modified by C-peptide level. Higher baseline circulating ghrelin level was independently associated with a lower prognostic risk for CKD. LIMITATIONS: A minority of participants had baseline CKD; lack of comparison group; no information on duration of diabetes, other clinical end points, or kidney biopsy results. CONCLUSIONS: Remission of type 2 diabetes 5 years after bariatric surgery was associated with improvements in albuminuria and stabilized prognostic risk for CKD, but not with eGFR. Lower kidney function and greater prognostic risk at the time of bariatric surgery was linked to a lower likelihood of diabetes remission. These results highlight the need to identify the mechanisms through which bariatric surgery may delay the long-term progression of CKD in type 2 diabetes.

Disturbance of gut satiety peptide in purging disorder.

OBJECTIVE: Little is known about biological factors that contribute to purging after normal amounts of food-the central feature of purging disorder (PD). This study comes from a series of nested studies examining ingestive behaviors in bulimic syndromes and specifically evaluated the satiety peptide YY (PYY) and the hunger peptide ghrelin in women with PD (n = 25), bulimia nervosa-purging (BNp) (n = 26), and controls (n = 26). Based on distinct subjective responses to a fixed meal in PD (Keel, Wolfe, Liddle, DeYoung, & Jimerson, ), we tested whether postprandial PYY response was significantly greater and ghrelin levels significantly lower in women with PD compared to controls and women with BNp. METHOD: Participants completed structured clinical interviews, self-report questionnaires, and laboratory assessments of gut peptide and subjective responses to a fixed meal. RESULTS: Women with PD demonstrated a significantly greater postprandial PYY response compared to women with BNp and controls, who did not differ significantly. PD women also endorsed significantly greater gastrointestinal distress, and PYY predicted gastrointestinal intestinal distress. Ghrelin levels were significantly greater in PD and BNp compared to controls, but did not differ significantly between eating disorders. Women with BNp endorsed significantly greater postprandial hunger, and ghrelin predicted hunger. DISCUSSION: PD is associated with a unique disturbance in PYY response. Findings contribute to growing evidence of physiological distinctions between PD and BNp. Future research should examine whether these distinctions account for differences in clinical presentation as this could inform the development of specific interventions for patients with PD.

Comparatively study on the insulin-regulated glucose homeostasis through brain-gut peptides in Japanese flounder Paralichthys olivaceus after intraperitoneal and oral administration of glucose.

The present study comparatively analyzed the blood glucose and insulin concentration, the temporal and spatial expression of brain-gut peptides and the key enzymes of glycolysis and gluconeogenesis in Japanese flounder by intraperitoneal injection (IP) and oral administration (OR) of glucose. Samples were collected at 0, 1, 3, 5, 7, 9, 12, 24 and 48 h after IP and OR glucose, respectively. Results showed that the hyperglycemia lasted for about 10 h and 21 h in OR and IP group, respectively. The serum insulin concentration significantly decreased at 3 h (1.58 ±â€¯0.21 mIU/L) after IP glucose. However, it significantly increased at 3 h (3.37 ±â€¯0.341 mIU/L) after OR glucose. The gene expressions of prosomatostatin, neuropeptide Y, cholecystokinin precursor and orexin precursor in the brain showed different profiles between the OR and IP group. The OR not IP administration of glucose had significant effects on the gene expressions of preprovasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide and gastrin in intestine. In conclusion, brain-gut peptides were confirmed in the present study. And the serum insulin and the brain-gut peptides have different responses between the IP and OR administration of glucose. The OR could stimulate the brain-gut peptide expressions, which have effects on the insulin secretion and then regulate the blood glucose levels. However, in IP group, there is little chance to stimulate brain-gut peptide expression to influence the insulin secretion, which leads to a longer hyperglycemia.

Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.

BACKGROUND: High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption. METHODS: Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate. RESULTS: At baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories). CONCLUSION: Consuming 30 g HAM-RS2 daily for 6 weeks can improve glucose homeostasis, lower leptin concentrations, and increase fasting PYY in healthy overweight adults without impacting body composition and may aid in the prevention of chronic disease. However, between-group differences in biomarkers were not observed and future research is warranted before specific recommendations can be made. TRIAL REGISTRATION: None.

Jejunal Infusion of Glucose Decreases Energy Intake to a Greater Extent than Fructose in Adult Male Rats.

BACKGROUND: Intestinal nutrient infusions result in variable decreases in energy intake and body weight based on nutrient type and specific intestinal infusion site. OBJECTIVE: The objective was to test whether an intrajejunal fructose infusion (FRU) would lower energy intake and body weight and induce similar increases in gut hormones as those found after intrajejunal glucose infusions (GLU). METHODS: Male Sprague-Dawley rats received an intrajejunal infusion of either an equal kilocalorie load of glucose or fructose (11.4 kcal) or saline (SAL) for 5 d while intake of a standard rodent diet was continuously recorded; body weight was measured daily. Immediately after the infusion on the final day, rats were killed and plasma was collected to measure hormones. RESULTS: Daily energy intake was significantly lower in the GLU group than in the SAL group, but the FRU group did not differ from the GLU or SAL groups when the 11.4 kcal of the infusate was included as energy intake. Lower energy intake was due to smaller meal sizes during the infusion period in the GLU group than in the FRU and SAL groups; the FRU and SAL groups did not differ. The percentage of change in body weight was lower in the GLU group than in the FRU and SAL groups. Plasma glucagon-like-peptide 1 (GLP-1) concentrations were greater in the GLU group than in the SAL group; the FRU group did not differ from the GLU or SAL groups. The plasma insulin concentration was greater in the FRU group than in both the GLU and SAL groups. CONCLUSION: These results demonstrate that glucose induces a greater decrease in energy intake and increase in GLP-1 at distal intestinal sites than fructose in rats, which may explain differential effects of these monosaccharides between studies when delivered orally or along the proximal to distal axis of the intestine.

The Gut as an Endocrine Organ: Role in the Regulation of Food Intake and Body Weight.

UNLABELLED: Obesity and its related complications remain a major threat to public health. Efforts to reduce the prevalence of obesity are of paramount importance in improving population health. Through these efforts, our appreciation of the role of gut-derived hormones in the management of body weight has evolved and manipulation of this system serves as the basis for our most effective obesity interventions. PURPOSE OF THE REVIEW: We review current understanding of the enteroendocrine regulation of food intake and body weight, focusing on therapies that have successfully embraced the physiology of this system to enable weight loss. RECENT FINDINGS: In addition to the role of gut hormones in the regulation of energy homeostasis, our understanding of the potential influence of enteroendocrine peptides in food reward pathways is evolving. So too is the role of gut derived hormones on energy expenditure. Gut-derived hormones have the ability to alter feeding behavior. Certain obesity therapies already manipulate this system; however, our evolving understanding of the effects of enteroendocrine signals on hedonic aspects of feeding and energy expenditure may be crucial in identifying future obesity therapies.

Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes.

Obesity is associated with a systemic chronic low-grade inflammation that contributes to the development of metabolic disorders such as cardiovascular diseases and type 2 diabetes. However, the etiology of this obesity-related pro-inflammatory process remains unclear. Most studies have focused on adipose tissue dysfunctions and/or insulin resistance in skeletal muscle cells as well as changes in adipokine profile and macrophage recruitment as potential sources of inflammation. However, low-grade systemic inflammation probably involves a complex network of signals interconnecting several organs. Recent evidences have suggested that disturbances in the composition of the gut microbial flora and alterations in levels of gut peptides following the ingestion of a high-fat diet may be a cause of low-grade systemic inflammation that may even precede and predispose to obesity, metabolic disorders or type 2 diabetes. This hypothesis is appealing because the gastrointestinal system is first exposed to nutrients and may thereby represent the first link in the chain of events leading to the development of obesity-associated systemic inflammation. Therefore, the present review will summarize the latest advances interconnecting intestinal mucosal bacteria-mediated inflammation, adipose tissue and skeletal muscle in a coordinated circuitry favouring the onset of a high-fat diet-related systemic low-grade inflammation preceding obesity and predisposing to metabolic disorders and/or type 2 diabetes. A particular emphasis will be given to high-fat diet-induced alterations of gut homeostasis as an early initiator event of mucosal inflammation and adverse consequences contributing to the promotion of extended systemic inflammation, especially in adipose and muscular tissues.

Gut microbiota, nutrient sensing and energy balance.

The gastrointestinal (GI) tract is a highly specialized sensory organ that provides crucial negative feedback during a meal, partly via a gut-brain axis. More specifically, enteroendocrine cells located throughout the GI tract are able to sense and respond to specific nutrients, releasing gut peptides that act in a paracrine, autocrine or endocrine fashion to regulate energy balance, thus controlling both food intake and possibly energy expenditure. Furthermore, the gut microbiota has been shown to provide a substantial metabolic and physiological contribution to the host, and metabolic disease such as obesity has been associated with aberrant gut microbiota and microbiome. Interestingly, recent evidence suggests that the gut microbiota can impact the gut-brain axis controlling energy balance, at both the level of intestinal nutrient-sensing mechanisms, as well as potentially at the sites of integration in the central nervous system. A better understanding of the intricate relationship between the gut microbiota and host energy-regulating pathways is crucial for uncovering the mechanisms responsible for the development of metabolic diseases and for possible therapeutic strategies.

Systematic review and meta-analysis of gut peptides expression during fasting and postprandial states in individuals with obesity.

Gut peptides play a role in signaling appetite control in the hypothalamus. Limited knowledge exists regarding the release of these peptides in individuals with obesity before and during external stimuli. We hypothesize that the expression of gut peptides is different in the fasting and postprandial states in the scenario of obesity. PubMed/MEDLINE, Scopus, and Science Direct electronic databases were searched. The meta-analysis was performed using Review Manager Software. Randomized controlled trials that measured gut peptides in both obese and lean subjects were included in the analysis. A total of 552 subjects with obesity were enrolled in 25 trials. The gut peptide profile did not show any significant difference between obese and lean subjects for glucagon-like peptide 1 (95% confidence interval [CI], -1.21 to 0.38; P = .30), peptide YY (95% CI, -1.47 to 0.18; P = .13), and cholecystokinin (95% CI, -1.25 to 1.28; P = .98). Gut peptides are decreased by an increased high-fat, high-carbohydrate diet and by decreased chewing. There is no statistically significant difference in gut peptides between individuals with obesity and leanness in a fasting state. However, the release of gut peptides is affected in individuals with obesity following external stimuli, such as dietary interventions and chewing. Further studies are necessary to investigate the relationship between various stimuli and the release of gut peptides, as well as their impact on appetite regulation in subjects with obesity.