Gut Hormones and Appetite Control: A Focus on PYY and GLP-1 as Therapeutic Targets in Obesity

The global obesity epidemic has resulted in significant morbidity and mortality. However, the medical treatment of obesity is limited. Gastric bypass is an effective surgical treatment but carries significant perioperative risks. The gut hormones, peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP-1), are elevated following gastric bypass and have been shown to reduce food intake. They may provide new therapeutic targets. This review article provides an overview of the central control of food intake and the role of PYY and GLP-1 in appetite control. Key translational animal and human studies are reviewed

GLP-1, DPP-4 and GPCR Levels in Diabetic and Diabetic neuropathy Patient`s

Background: Neuropathy is a common disorder in DM patients which results from poor glycaemic control and long duration of diabetes. Higher body mass index, smoking, hypertension, hypercholesterolemia and hypertriglyceridemia are associated with the incidence of neuropathy. Objective: The aim of this study is to estimate glucagon like Peptide-1, DPP-4 and G-Protein coupled Receptor levels in diabetic and diabetic neuropathy and to compares the results with control group. Also, to find the correlation of GPCR with GLP-1 and DPP-4 in all studied groups.Subjects and Methods: ninety subjects were enrolled in this study with aged ranged (40-65) years and BMI with (30-35) Kg/m2 that divided into three groups as follows: group one (G1) consists of 30 healthy individuals as a control group, group two (G2) consists of 30 patients with diabetic and group three (G3) consists of 30 patients with diabetic and neuropathy as complication. ESC(Feet Mean), ESC(Hand Mean), ESC(Risk of neuropathies), HbA1C, GLP-1, DPP-4 and GPCR  were determined.Results: The result showed highly significant elevation in HbA1C levels in patients groups comparing to control group. Results, also a highly significant elevation in GLP-1 and DPP-4 levels in G2 comparing to G1, and in G3 comparing to G2 and G1 were noticed. A highly significant elevation in GPCR levels in G2 comparing to G1and G3, while no significant increased noticed in G3 comparing to G2. A high significant positive correlation was found between GLP-1 and DPP-4 in G1, while highly significant negative correlation was found in G2 and G3. A high significant positive correlation was observed between GLP-1 and GPCR in G1. Moreover, No significant positive correlation was observed in G2, but a significant positive correlation was observed in G3. High significant negative correlation was found between GPCR and DPP-4 in G1 and G2, while a high significant positive correlation was found in G3. Conclusion: the conclusion is obtained from this study that GLP-1and GPCR have important role in development of neuro injury in neurodiabetic patients. Also, correlation was found between GPCR with GLP-1 and DPP-4. Keywords: Diabetic neuropathy, GLP-1, DPP-4 and GPCR

The Gut Hormones in Appetite Regulation

Obesity has received much attention worldwide in association with an increased risk of cardiovascular diseases, diabetes, and cancer. At present, bariatric surgery is the only effective treatment for obesity in which long-term weight loss is achieved in patients. By contrast, pharmacological interventions for obesity are usually followed by weight regain. Although the exact mechanisms of long-term weight loss following bariatric surgery are yet to be fully elucidated, several gut hormones have been implicated. Gut hormones play a critical role in relaying signals of nutritional and energy status from the gut to the central nervous system, in order to regulate food intake. Cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin act through distinct yet synergistic mechanisms to suppress appetite, whereas ghrelin stimulates food intake. Here, we discuss the role of gut hormones in the regulation of food intake and body weight

The Gut–Brain Axis and Its Role in Controlling Eating Behavior in Intestinal Inflammation

Malnutrition represents a major problem in the clinical management of the inflammatorybowel disease (IBD). Presently, our understanding of the cross-link between eating behavior andintestinal inflammation is still in its infancy. Crohn’s disease patients with active disease exhibit stronghedonic desires for food and emotional eating patterns possibly to ameliorate feelings of low mood,anxiety, and depression. Impulsivity traits seen in IBD patients may predispose them to palatablefood intake as an immediate reward rather than concerns for future health. The upregulation ofenteroendocrine cells (EEC) peptide response to food intake has been described in ileal inflammation,which may lead to alterations in gut–brain signaling with implications for appetite and eatingbehavior. In summary, a complex interplay of gut peptides, psychological, cognitive factors, diseaserelatedsymptoms, and inflammatory burden may ultimately govern eating behavior in intestinalinflammation

A functional neuroimaging review of obesity, appetitive hormones and ingestive behavior

Adequate energy intake is vital for the survival of humans and is regulated by complex homeostatic and hedonic mechanisms. Supported by functional MRI (fMRI) studies that consistently demonstrate differences in brain response as a function of weight status during exposure to appetizing food stimuli, it has been posited that hedonically driven food intake contributes to weight gain and obesity maintenance. These food reward theories of obesity are reliant on the notion that the aberrant brain response to food stimuli relates directly to ingestive behavior, specifically, excess food intake. Importantly, functioning of homeostatic neuroendocrine regulators of food intake, such as leptin and ghrelin, are impacted by weight status. Thus, data from studies that evaluate the effect of weight status on brain response to food may be a result of differences in neuroendocrine functioning and/or behavior. In the present review, we examine the influence of weight and weight change, exogenous administration of appetitive hormones, and ingestive behavior on BOLD response to food stimuli

The Effects of an Acute Bout of Exercise on Hunger Hormones in Individuals at Risk for Type 2 Diabetes

Background: Hunger hormone levels are typically dysregulated in obese and diabetic populations, however; postprandial exercise has been shown to influence hunger hormone levels. Purpose: To determine if hunger hormones including acylated ghrelin and GLP-1 levels are altered in response to an acute bout (15 minutes) of walking in individuals at risk for type 2 diabetes mellitus (T2DM). Methods: Ten subjects at risk for prediabetes (fasting blood glucose 100–125mg/dL) participated in this randomized crossover design trial. Subjects arrived at the laboratory following an overnight fast and underwent one of two conditions: 1) Test meal with no walking (CON) or 2) Test meal followed by a 15-minute treadmill walk at preferred walking speed (WALK). Blood samples were taken over two hours and assayed for acylated ghrelin and active GLP-1. A repeated measures ANOVA was used to compare mean differences for all outcome variables. Results: There were no statistical differences in acylated ghrelin (F = 1.535, p = 0.247) or GLP-1 (F = 0.003, p = 0.955) concentrations between CON and WALK conditions at any time period. There was a main effect of time for ghrelin (F = 41.339; p \u3c 0.001). Post hoc analysis indicated a significant difference between baseline and 60 minutes (p \u3c 0.001) and between baseline and 120 minutes (p \u3c 0.001) for acylated ghrelin concentrations. No difference was found between 60 minutes and 120 minutes (p = 0.834). There was a main effect of time for GLP-1 (F = 17.968; p \u3c 0.001). Post hoc analysis indicated a significant difference between baseline and 60 minutes (p = 0.001) and between baseline and 120 minutes (p = 0.002) for GLP-1 concentrations. No difference was found between 60 minutes and 120 minutes (p = 0.665). There was no significant difference in the AUC for acylated ghrelin between the CON and WALK conditions (t = -1.257; p = 0.240). There was no significant difference in the AUC for GLP-1 between the CON and WALK conditions (t = -0.107; p = 0.918). Correlations between perceived hunger and biological hunger were weak and nonsignificant (p \u3e 0.05). Conclusion: A 15-minute walk performed shortly after a meal does not have a significant impact on hunger hormones including acylated ghrelin and active GLP-1 concentrations in individuals at risk for T2DM

Regulation of Food Intake in Adults with and without Obesity: The Role of the Gastrointestinal Tract and Gut-Brain Axis

Obesity is a complex global health issue affecting a significant portion of the population. In the UK, it is estimated that approximately 1 in 4 adults and 1 in 5 children aged 10 to 11 years are living with obesity. Impairment in food intake regulation, including hunger and satiety sensations, are key factors contributing to overeating and weight gain, particularly in individuals with obesity. While various mechanisms may explain these alterations, such as altered appetite and satiety regulators, accelerated gastric emptying (GE), and heightened brain responses to food cues and reward, it remains inconclusive whether these mechanisms are altered in people living with obesity compared to normalweight (NW) adults. There are various approaches to studying food regulation, each offering unique insights into the complex mechanisms that control appetite, satiety, and food intake. Non-invasive imaging, particularly magnetic resonance imaging (MRI), provides a powerful tool for investigating the physiological mechanisms underlaying the regulation of food intake. The work in this PhD thesis aims to combine physiological measurements obtained by using MRI with behavioural assessments (i.e., subjective satiety rating), to provide a more comprehensive understanding of appetite control in NW adults and alterations associated with obesity. The work in this thesis included a functional neuroimaging metaanalysis, and three eating behaviour intervention studies, two of which used MRI techniques. A functional neuroimaging meta-analysis was performed to identify brain areas associated with changes in appetite and satiety regulators in NW and Obese adults. The caudate nucleus and hypothalamus were identified as key areas associated with satiety regulators in NW participants. However, conclusive findings for Obese participants were limited due to the small number of studies conducted in this area. An MRI study was conducted to investigate the effect of a standard meal on gastrointestinal (GI) responses. The study found that GI responses including gastric content volume (GCV), GE rate, small bowel water content (SBWC), and superior mesenteric artery (SMA) blood flow, and appetite and satiety regulators were not significantly altered by obesity following the meal. However, Obese participants showed lower satiety subjective rating, and higher insulin and triglyceride levels compared to NW participants. Different macronutrients play distinct roles in influencing feelings of fullness and satiety, and their impact on the satiety sensation can be a valuable strategy for weight loss. In a pilot MRI study combining gut and brain imaging, responses to a high-fat (HF) emulsion drink and a carbohydrate drink that is matched in caloric content, volume, and viscosity were assessed in NW and Obese participants. Data collection in this study was significantly impacted by the COVID pandemic; therefore, findings from this work are focused on GI responses. The results suggest that the HF drink might induce higher GCV, SBWC, SMA blood flow, and subjective satiety ratings when compared to an iso-caloric, and iso-viscous high carbohydrate drink (HC) in both NW and Obese. The final study investigated the satiating effect of acute high protein consumption compared to high carbohydrate in NW and Obese participants using ad libitum meal intake and subjective satiety ratings. This study found no significant differences in ad libitum energy intake, subjective satiety, or energy intake between the drinks in either NW or Obese participants. This research integrated different approaches to measuring the regulation of food intake and alterations in obesity. This holistic approach facilitates a comprehension understanding of the mechanisms governing food regulation, including the impact of macronutrient composition, hormonal influences, gastrointestinal responses, neural signalling, and eating behaviours. While the studies in the thesis did not reveal significant differences in certain aspects of appetite regulation between NW and Obese, including macronutrient compositions, they did highlight several areas requiring further investigations. The complicated nature of obesity and appetite regulation necessitates continued research to better understand these complex mechanisms and inform strategies for obesity management and prevention