Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index

2014 ◽  
Vol 307 (10) ◽  
pp. G958-G967 ◽  
Author(s):  
Tanya J. Little ◽  
Nicole J. Isaacs ◽  
Richard L. Young ◽  
Raffael Ott ◽  
Nam Q. Nguyen ◽  
...  

Fatty acids (FAs) stimulate the secretion of gastrointestinal hormones, including cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1), which suppress energy intake. In obesity, gastrointestinal responses to FAs are attenuated. Recent studies have identified a key role for the FA-sensing receptors cluster of differentiation (CD)36, G protein-coupled receptor (GPR)40, GPR120, and GPR119 in mediating gastrointestinal hormone secretion. This study aimed to determine the expression and localization of these receptors in the duodenum of humans and to examine relationships with obesity. Duodenal mucosal biopsies were collected from nine lean [body mass index (BMI): 22 ± 1 kg/m2], six overweight (BMI: 28 ± 1 kg/m2), and seven obese (BMI: 49 ± 5 kg/m2) participants. Absolute levels of receptor transcripts were quantified using RT-PCR, while immunohistochemistry was used for localization. Transcripts were expressed in the duodenum of lean, overweight, and obese individuals with abundance of CD36>>GPR40>GPR120>GPR119. Expression levels of GPR120 ( r = 0.46, P = 0.03) and CD36 ( r = 0.69, P = 0.0004) were directly correlated with BMI. There was an inverse correlation between expression of GPR119 with BMI ( r2 = 0.26, P = 0.016). Immunolabeling studies localized CD36 to the brush border membrane of the duodenal mucosa and GPR40, GPR120, and GPR119 to enteroendocrine cells. The number of cells immunolabeled with CCK ( r = −0.54, P = 0.03) and GLP-1 ( r = −0.49, P = 0.045) was inversely correlated with BMI, such that duodenal CCK and GLP-1 cell density decreased with increasing BMI. In conclusion, CD36, GPR40, GPR120, and GPR119 are expressed in the human duodenum. Transcript levels of duodenal FA receptors and enteroendocrine cell density are altered with increasing BMI, suggesting that these changes may underlie decreased gastrointestinal hormone responses to fat and impaired energy intake regulation in obesity.

2007 ◽  
Vol 293 (3) ◽  
pp. E743-E753 ◽  
Author(s):  
Amelia N. Pilichiewicz ◽  
Reawika Chaikomin ◽  
Ixchel M. Brennan ◽  
Judith M. Wishart ◽  
Christopher K. Rayner ◽  
...  

Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 (“G1”), 2) 2 (“G2”), and 3) 4 (“G4”) kcal/min or of 4) saline (“control”) were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions ( P < 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 ( P < 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load ( r > 0.82, P < 0.05). All glucose infusions suppressed antral ( P < 0.05), but only G4 decreased duodenal, pressure waves ( P < 0.01), resulted in a sustained stimulation of basal pyloric pressure ( P < 0.01), and decreased energy intake ( P < 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1104
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Richard L. Young ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
...  

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.


2003 ◽  
Vol 88 (12) ◽  
pp. 5914-5920 ◽  
Author(s):  
Yumi Matsushita ◽  
Tetsuji Yokoyama ◽  
Nobuo Yoshiike ◽  
Yasuhiro Matsumura ◽  
Chigusa Date ◽  
...  

Abstract The β3-adrenergic receptor (ADRB3) is expressed mainly in visceral adipose tissue and is thought to contribute to lipolysis and the delivery of free fatty acids to the portal vein. Although many studies have examined the relationship between the Trp64Arg mutation of ADRB3 and obesity, the results have been inconsistent. We examined the cross-sectional relationship of ADRB3 variants with indexes of obesity, and their longitudinal changes over 10 yr, in men and women, aged 40–69 yr, who were randomly selected from the Japanese rural population. The study considered both dietary energy intake and physical activity levels. Among the 746 participants, the genotype frequencies of the Trp64Trp, Trp64Arg, and Arg64Arg variants were 483, 224, and 39, respectively. The cross-sectional analysis showed no significant differences in height, weight, body mass index, blood pressure, serum total and high density lipoprotein cholesterols, and hemoglobin A1c among the genotype groups even after adjustments for gender, age, smoking, alcohol drinking, physical activity, and energy intake. No significant differences in the weight changes between the genotype groups were evident in the longitudinal analysis. We conclude that the Trp64Arg mutation of ADRB3 has little or no influence on either body weight or body mass index in the general Japanese population.


2017 ◽  
Vol 30 (4) ◽  
pp. 455-461
Author(s):  
Priscila Francisco MARQUES ◽  
Maria Angela Bellomo BRANDÃO ◽  
Gabriel HESSEL ◽  
Roberta Vacari ALCANTARA ◽  
Marcela Linden FERREIRA ◽  
...  

ABSTRACT Objective: This study aims to evaluate dietary intake, nutritional status, and growth rate in children and adolescents with extrahepatic portal vein obstruction and portal hypertension. Methods: Outpatients aged 1-18 years, diagnosed with extrahepatic portal vein obstruction and portal hypertension, who had no associated diseases, and who had not been subjected to a venous shunt were included in this study. Two evaluations were carried out in this study: an initial (evaluation 1) and a final evaluation (evaluation 2), with a three-month minimum interval between them. In each evaluation, dietary intake was analyzed comparing the results with recommended energy intake using the Harris & Benedict equation and participants’ anthropometric data, such as weight, height, mid-arm muscle circumference, weight-for-age, height-for-age, and body mass index-for-age, based on the World Health Organization 2006 standards. Results: A total of 22 patients participated in this study. There was a significant improvement in weight, height, body mass index, and mid-arm muscle circumference measurements (p<0.001; p<0.001; p<0.017; p=0.0018 respectively) and in the relationship between dietary intake and energy recommended energy intake, according to the Harris & Benedict equation (p=0.0001) from the first and second evaluation. Conclusion: Extrahepatic portal vein obstruction and portal hypertension were not shown to be factors predisposing to malnourishment.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jeremy D. Coplan ◽  
Shariful Syed ◽  
Tarique D. Perera ◽  
Sasha L. Fulton ◽  
Mary Ann Banerji ◽  
...  

Glucagon-like peptide-1 (GLP-1) regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1), and body mass index (BMI) in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.


2018 ◽  
Vol 113 ◽  
pp. 91-99 ◽  
Author(s):  
Jerry L. Campbell ◽  
Miyoung Yoon ◽  
Peyton L. Ward ◽  
Hermann Fromme ◽  
Winfried Kessler ◽  
...  

Author(s):  
Raquel Barba ◽  
Josep Bisbe ◽  
José Nicolas Alcalá Pedrajas ◽  
Jesús Toril ◽  
Rafael Monte ◽  
...  

Background The relationship between body mass index (BMI) and mortality in patients with established arterial disease remains controversial. Methods FRENA is an ongoing, observational registry of consecutive outpatients with coronary artery disease (CAD), cerebrovascular disease, or peripheral artery disease (PAD). We examined the prognostic importance of accepted BMI categories on outcome among patients in the FRENA registry. Results In April 2008, 2274 patients (mean age, 66 years) had been enrolled, of whom 14 (0.6%) were underweight; 533 (23%) normal; 1051 (46%) overweight; and 676 (30%) were obese. Over a mean follow-up of 14 months, the incidence of major cardiovascular events (myocardial infarction, ischemic stroke, or critical limb ischemia) per 100 patient-years was: 7.1 [95% confidence interval (CI): 0.4–35]; 11 (95% CI: 8.4–14); 6.9 (95% CI: 5.6–8.5); and 8.5 (95% CI: 6.6–11), respectively. Their cardiovascular mortality was: 7.1 (95% CI: 0.4–35); 4.1 (95% CI: 5.9–11); 1.3 (95% CI: 0.9–2.3); and 1.5 (95% CI: 1.4–3.5), respectively. On multivariate analysis, the hazard ratio for cardiovascular mortality was: 2.2 (95% CI: 0.3–17); 1.0 (reference); 0.37 (95% CI: 0.20–0.69); and 0.37 (95% CI: 0.18–0.73), respectively. Survival benefit was only found in patients with CAD or PAD. Weight loss had little influence on outcome. Conclusion Patients with CAD or PAD (not those with cerebrovascular disease) have an inverse correlation between BMI and cardiovascular mortality, even after adjusting for confounding variables.


Medicina ◽  
2006 ◽  
Vol 43 (1) ◽  
pp. 10 ◽  
Author(s):  
Gražina Drąsutienė ◽  
Janina Tutkuvienė ◽  
Jolita Zakarevičienė ◽  
Diana Ramašauskaitė ◽  
Žaneta Kasilovskienė ◽  
...  

Objective. To evaluate changes in anthropometric and biochemical parameters in pregnancy and their dynamics during last two decades and to determine the association between anthropometric and biochemical parameters, their influence on fetal and neonatal development. Material and methods. In 1985–2005, anthropometric (height, body mass, weight gain during pregnancy, pelvic measurements, skinfold thicknesses, passive body mass) and biochemical (cholesterol, triglyceride, protein, and iron levels) parameters, their correlation, changes in pregnancy were examined; also the correlations between these parameters and neonatal body mass indices were evaluated. In 1986–1987, 383 pregnant women were examined, in 1998 – 130, and in 2003–2005 – 133. Results. During 20 years, the height of examined women increased on an average of 2.5 cm; they became thinner; body mass index decreased. The body composition became similar to “cylinder” shape due to decreased thickness of adipose tissue in the limbs. The dimensions of bony pelvis – external conjugate and bicristal diameters – decreased. Primiparous women became older (1995 – 22.5 years of age, 2004 – 27.6). At the beginning of investigation, the weight gain was on an average of 21.9% of body mass before pregnancy (13.3 kg) and at the end – 23.9% (14.2 kg). The values of anthropometric parameters vary in a consistent pattern during pregnancy: the lower body mass and body mass index at the beginning of pregnancy, the higher weight gain at the end of pregnancy. Blood serum levels of cholesterol, triglycerides, and especially iron were decreased during the study. Conclusions. An inverse correlation between body mass index and lipid metabolism in pregnancy was revealed: the higher body mass index was at the beginning of pregnancy, the lower increase in lipid concentration was during pregnancy. At the beginning of investigation as well as after 20 years, women with low body mass index showed the most significant anthropometric and lipid metabolic changes in pregnancy.


2008 ◽  
Vol 74 (6) ◽  
pp. 469-475 ◽  
Author(s):  
Ronald H. Clements ◽  
Kishore Yellumahanthi ◽  
Mary Wesley ◽  
Naveen Ballem ◽  
Kirby I. Bland

Hyperparathyroidism (HPT) can occur after gastric bypass because of the alteration in vitamin D and calcium absorption. Adequate serum vitamin D concentrations have not been clearly defined in this patient population. Vitamin D (Vit D) and parathyroid hormone (PTH) were assessed 1 year after laparoscopic gastric bypass (LGB). The prevalence of HPT and Vit D deficiency were determined and their association was evaluated using Fisher's exact test. Ninety-three patients (aged 44 ± 1.1 years, 49.6 ± 0.67 kg/m2 body mass index, 79.6% female, 69.6% white) were evaluated. The prevalence of Vit D deficiency (less than 20 ng/mL) and HPT (greater than 65 pg/mL) was 23.6 per cent (n = 22) and 25.7 per cent (n = 28), respectively. Among patients with HPT, only eight of 28 (28.6%) had Vit D deficiency, and of those with Vit D deficiency, only eight of 22 (36.4%) had HPT. There was a weak inverse correlation (r = –0.37) between PTH and Vit D. Blacks are at higher risk for Vit D deficiency. There was no significant association between Vit D deficiency and HPT, Vit D deficiency and Roux limb length, or HPT and Roux limb length. After LGB, Vit D deficiency and hyperparathyroidism occur commonly. Body mass index and Roux limb length are not associated with these two conditions, but racial differences do exist. There is a weak inverse correlation between Vit D and PTH. Further research is needed to elucidate the causes, treatments, and significance of HPT after LGB.


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