scholarly journals Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Joanna Michałowska ◽  
Ewa Miller-Kasprzak ◽  
Paweł Bogdański
Keyword(s):  
Treatment Strategies ◽  
Noncommunicable Diseases ◽  
Alcoholic Fatty Liver ◽  
Incretin Mimetics ◽  
Cardiometabolic Disorders ◽  
Public Health Challenges ◽  
Prevalence Of Obesity ◽  
Incretin Secretion ◽  
Obese Subjects ◽  
Glucagon Like Peptide 1

The prevalence of obesity continues to grow rapidly worldwide, posing many public health challenges of the 21st century. Obese subjects are at major risk for serious diet-related noncommunicable diseases, including type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Understanding the mechanisms underlying obesity pathogenesis is needed for the development of effective treatment strategies. Dysregulation of incretin secretion and actions has been observed in obesity and related metabolic disorders; therefore, incretin-based therapies have been developed to provide new therapeutic options. Incretin mimetics present glucose-lowering properties, together with a reduction of appetite and food intake, resulting in weight loss. In this review, we describe the physiology of two known incretins—glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and their role in obesity and related cardiometabolic disorders. We also focus on the available and incoming incretin-based medications that can be used in the treatment of the above-mentioned conditions.

scholarly journals Roles of Gut-Derived Secretory Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Their Possible Clinical Applications

2018 ◽  
Vol 19 (10) ◽  
pp. 3064 ◽  
Author(s):  
Hirofumi Okubo ◽  
Akifumi Kushiyama ◽  
Yusuke Nakatsu ◽  
Takeshi Yamamotoya ◽  
Yasuka Matsunaga ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Strategies ◽  
Alcoholic Fatty Liver ◽  
Glucagon Like Peptide 1 ◽  
Global Increase ◽  
Underlying Mechanisms ◽  
Alcoholic Fatty Liver Disease

The rising prevalence of non-alcoholic fatty liver disease (NAFLD) parallels the global increase in the number of people diagnosed with obesity and metabolic syndrome. The gut-liver axis (GLA) plays an important role in the pathogenesis of NAFLD/non-alcoholic steatohepatitis (NASH). In this review, we discuss the clinical significance and underlying mechanisms of action of gut-derived secretory factors in NAFLD/NASH, focusing on recent human studies. Several studies have identified potential causal associations between gut-derived secretory factors and NAFLD/NASH, as well as the underlying mechanisms. The effects of gut-derived hormone-associated drugs, such as glucagon-like peptide-1 analog and recombinant variant of fibroblast growth factor 19, and other new treatment strategies for NAFLD/NASH have also been reported. A growing body of evidence highlights the role of GLA in the pathogenesis of NAFLD/NASH. Larger and longitudinal studies as well as translational research are expected to provide additional insights into the role of gut-derived secretory factors in the pathogenesis of NAFLD/NASH, possibly providing novel markers and therapeutic targets in patients with NAFLD/NASH.

scholarly journals The Pattern of Fasting and Post 75 G Glucose Loading of Glucagon-Like Peptide 1 Levels in Obese and Non-Obese Subjects

2019 ◽  
Vol 7 (3) ◽  
pp. 358-362
Author(s):  
Ida Bagus Aditya Nugraha ◽  
Made Ratna Saraswati ◽  
Ketut Suastika
Keyword(s):  
Fasting State ◽  
Glucose Loading ◽  
Cardiometabolic Diseases ◽  
Prevalence Of Obesity ◽  
Obese Subjects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Difference ◽  
Time Observation ◽  
Age And Sex

BACKGROUND: Prevalence of obesity increased sharply recently; it was associated with an increased prevalence of several cardiometabolic diseases. Reduced glucagon-like peptide 1 (GLP-1) secretion is observed among obese subjects in many studies, and it may mediate the failure of insulin secretion response to food intake. AIM: To evaluate the pattern of fasting and post 75 g glucose loading of GLP-1 levels in obese and non-obese subjects. METHODS: An experimental study on the pattern of GLP-1 levels in fasting state and response in post 75 g glucose loading in obese and non-obese subjects, was conducted. Sixteen obese and 16 non-obese subjects were enrolled in the study, with age- and sex-matching in both groups. GLP-1 levels were measured at fasting state (0), 15, 30, 60, and 120 minutes post-glucose loading. RESULTS: The GLP-1 response to glucose loading were similar in obese and non-obese subjects, which increased from fasting state to post glucose loading and reaching the peak levels in 15 minutes, then declined until the end of observation. There was tendency that GLP-1 levels in fasting state and post glucose loading were lower in obese subjects compared to in non-obese subjects (in fasting state, 5.67 vs. 6.16 ng/mL, P = 0.338; in 15 minutes, 6.20 vs. 6.94 ng/mL, P = 0.239; in 30 minutes 6.20 vs. 6.90 ng/mL, P = 0.264; in 60 minutes, 5.77 vs. 6.12 ng/mL, P = 0.242), but the difference were not statistically significant, except in 120 minutes (5.24 vs. 6.67 ng/mL, P = 0.049; in obese and non-obese subjects, respectively). Similar finding was also seen in the pattern of response (delta) of GLP-1 from time-to-time observation among obese and non-obese subjects (0-15 minutes [0.52 vs. 0.8 ng/mL, P = 0.350], 0-30 minutes [0.53 vs. 0.74, P = 0.550], 0-60 minutes [0.11 vs. 0.31 ng/mL, P = 0.546], in 0-120 minute [-0.42 vs. 0.31, P = 0.006]). CONCLUSIONS: The patterns of GLP-1 levels post glucose loading were similar in obese and non-obese subjects which increased from fasting state to post glucose loading, reaching the peak levels in 15 minutes and then declined until the end of observation, except in non-obese subjects where the GLP-1 levels were increased at 120 minutes. There was a tendency of GLP-1 levels in fasting state and post-glucose loading to be lower in obese subjects compared within non-obese subjects.

scholarly journals The albumin-to-alkaline phosphatase ratio as an independent predictor of future non-alcoholic fatty liver disease in a 5-year longitudinal cohort study of a non-obese Chinese population

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Guotai Sheng ◽  
Nan Peng ◽  
Chong Hu ◽  
Ling Zhong ◽  
Mingchun Zhong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Fatty Liver Disease ◽  
Chinese Population ◽  
Independent Predictor ◽  
Multiple Regression Model ◽  
Obese People ◽  
Alcoholic Fatty Liver ◽  
Obese Subjects ◽  
Alcoholic Fatty Liver Disease

Abstract Background The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. Methods The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. Results The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend< 0.0001). Additionally, there were significant interactions between the AAPR and BMI, blood pressure and lipids (P-interaction < 0.05). Stratified analysis showed that the risk of AAPR-related NAFLD decreased in people with normal blood pressure and lipid levels, while the risk of AAPR-related NAFLD increased abnormally in people who were underweight. Conclusions This longitudinal cohort study provides the first evidence that the AAPR is an independent predictor of future NAFLD events in non-obese people. For non-obese people with a low AAPR, especially those with BMI < 18.5 kg/m2, more attention should be given to the management of risk factors for NAFLD to prevent future NAFLD.

scholarly journals Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion

2018 ◽  
Vol 315 (4) ◽  
pp. E489-E495 ◽  
Author(s):  
Tanya J. Little ◽  
Nada Cvijanovic ◽  
Nicholas V. DiPatrizio ◽  
Donovan A. Argueta ◽  
Christopher K. Rayner ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Hormone Secretion ◽  
Intestinal Microbiome ◽  
Intestinal Alkaline Phosphatase ◽  
Toll Like Receptor 4 ◽  
Incretin Hormone ◽  
Incretin Secretion ◽  
Glucagon Like Peptide 1 ◽  
Factor Α ◽  
Insulinotropic Peptide

Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation; however, little is known of these effects in humans. This study aimed to 1) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl- sn-glycerol (2-AG), and OEA in humans; and 2) examine relationships to intestinal permeability, inflammation markers, and incretin hormone secretion. Twenty lean, 18 overweight, and 19 obese participants underwent intraduodenal Intralipid infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumor necrosis factor-α (TNFα), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and Toll-like receptor 4 (TLR4) (by RT-PCR) were assessed. Fasting plasma AEA was increased in obese compared with lean and overweight patients ( P < 0.05), with no effect of BMI group or ID lipid infusion on plasma 2-AG or OEA. Duodenal expression of IAP and ZO-1 was reduced in obese compared with lean ( P < 0.05), and these levels related negatively to plasma AEA ( P < 0.05). The iAUC for AEA was positively related to iAUC GIP ( r = 0.384, P = 0.005). Obese individuals have increased plasma AEA and decreased duodenal expression of ZO-1 and IAP compared with lean and overweight subjects. The relationships between plasma AEA with duodenal ZO-1, IAP, and GIP suggest that altered endocannabinoid signaling may contribute to changes in intestinal permeability, inflammation, and incretin release in human obesity.

Heart Failure with Preserved Ejection Fraction: Mechanisms and Treatment Strategies

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kazunori Omote ◽  
Frederik H. Verbrugge ◽  
Barry A. Borlaug
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Treatment Strategies ◽  
Annual Review ◽  
Publication Date ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Prevalence Of Obesity

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Glucose-Induced Glucagon-Like Peptide 1 Secretion Is Deficient in Patients with Non-Alcoholic Fatty Liver Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e87488 ◽  
Author(s):  
Christine Bernsmeier ◽  
Anne C. Meyer-Gerspach ◽  
Lea S. Blaser ◽  
Lia Jeker ◽  
Robert E. Steinert ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Alcoholic Fatty Liver Disease

scholarly journals Assessing longitudinal and cross-sectional effects of age on adult obesity in an Iranian population: results from a large population-based cohort study

2021 ◽  
Author(s):  
Mahsa Rafiee Alhossaini ◽  
Anoshirvan Kazemnejad ◽  
Farid Zayeri ◽  
Masoumeh Sadeghi
Keyword(s):  
Odds Ratio ◽  
Large Population ◽  
Significant Risk ◽  
High Rate ◽  
Noncommunicable Diseases ◽  
Public Health Issue ◽  
Related Factors ◽  
Cross Sectional ◽  
Longitudinal Effects ◽  
Prevalence Of Obesity

Abstract Background Obesity is a significant risk factor for Noncommunicable diseases, and it is related to many adverse health consequences. The risk of obesity commonly changes with age, which is called a longitudinal or aging effect. Also, individuals born or enter to the study of the same age have similar living conditions that may influence their obesity risk in a particular way; this is a cross-sectional effect. In the current study, an advanced statistical model is used to distinguish between longitudinal and cross-sectional effects of age on the risk of obesity for men and women. Methods Participants are a group of 6504 Iranian adults over 35 years of age in 2001, who live in the central region of Iran. They were followed up for 12 years in a large community-based study. Various medical indexes, including Body Mass Index, were collected in 2001, 2007, and 2013. The Marginal Logistic Regression model, which includes linear and quadratic effects of the Baseline Age and its difference with current age, is used. Results Between 2001 and 2013, the prevalence of obesity raised from 13% to 18% in men and from 31% to 44% in women. The odds of obesity for women was approximately three times the odds of obesity for men on average adjusting for the age effects. Both cross-sectional and longitudinal effects of age were significantly associated with the odds ratio of obesity. There was a rise in the prevalence of obesity for individuals with Baseline Age 35 to 55 and a decline thereafter. Also, the odds ratio of obesity across one’s life course, had about 3% increase, on average, by each year aging, regardless of the age at baseline. Conclusions The high rate of obesity and its fast growth is a serious public health issue among Iranians, especially in adults age 35-55, and women. In the present study, Baseline Age was more strongly associated with the risk of obesity than aging. Considering both cross-sectional and longitudinal effects of age, helps us to understand the effect of age on obesity better and to identify the related factors.

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