scholarly journals The Roles and Pharmacological Effects of FGF21 in Preventing Aging-Associated Metabolic Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Junbin Yan ◽  
Yunmeng Nie ◽  
Jielu Cao ◽  
Minmin Luo ◽  
Maoxiang Yan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Cellular Aging ◽  
Fibroblast Growth Factor 21 ◽  
Aging Effects ◽  
Dark Cloud ◽  
Alcoholic Fatty Liver ◽  
Glucose And Lipid Metabolism ◽  
Theoretical Support

With the continuous improvement of living standards but the lack of exercise, aging-associated metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) are becoming a lingering dark cloud over society. Studies have found that metabolic disorders are near related to glucose, lipid metabolism, and cellular aging. Fibroblast growth factor 21 (FGF21), a member of the FGFs family, efficiently regulates the homeostasis of metabolism and cellular aging. By activating autophagy genes and improving inflammation, FGF21 indirectly delays cellular aging and directly exerts anti-aging effects by regulating aging genes. FGF21 can also regulate glucose and lipid metabolism by controlling metabolism-related genes, such as adipose triglyceride lipase (ATGL) and acetyl-CoA carboxylase (ACC1). Because FGF21 can regulate metabolism and cellular aging simultaneously, FGF21 analogs and FGF21 receptor agonists are gradually being valued and could become a treatment approach for aging-associated metabolic diseases. However, the mechanism by which FGF21 achieves curative effects is still not known. This review aims to interpret the interactive influence between FGF21, aging, and metabolic diseases and delineate the pharmacology of FGF21, providing theoretical support for further research on FGF21.

scholarly journals Fibroblast growth factor 21: a regulator of metabolic disease and health span

2017 ◽  
Vol 313 (3) ◽  
pp. E292-E302 ◽  
Author(s):  
Ting Xie ◽  
Po Sing Leung
Keyword(s):  
Lipid Metabolism ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Metabolic Diseases ◽  
Scientific Basis ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Glucose And Lipid Metabolism ◽  
Care Guidelines

Fibroblast growth factor 21 (FGF21) is a potent endocrine regulator with physiological effects on glucose and lipid metabolism and thus garners much attention for its translational potential for the management of obesity and related metabolic syndromes. FGF21 is mainly expressed in several metabolically active tissue organs, such as the liver, adipose tissue, skeletal muscle, and pancreas, with profound effects and therapeutic relevance. Emerging experimental and clinical data point to the demonstrated metabolic benefits of FGF21, which include, but are not limited to, weight loss, glucose and lipid metabolism, and insulin sensitivity. In addition, FGF21 also acts directly through its coreceptor β-klotho in the brain to alter light-dark cycle activity. In this review, we critically appraise current advances in understanding the physiological actions of FGF21 and its role as a biomarker of various metabolic diseases, especially type 2 diabetes mellitus. We also discuss the potentially exciting role of FGF21 in improving our health and prolonging our life span. This information will provide a fuller understanding for further research into FGF21, as well as providing a scientific basis for potentially establishing health care guidelines for this promising molecule.

scholarly journals Hepatokines as a Molecular Transducer of Exercise

2021 ◽  
Vol 10 (3) ◽  
pp. 385
Author(s):  
Dae Yun Seo ◽  
Se Hwan Park ◽  
Jubert Marquez ◽  
Hyo-Bum Kwak ◽  
Tae Nyun Kim ◽  
...  
Keyword(s):  
Physical Activity ◽  
Metabolic Regulation ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Endocrine Organ ◽  
Nutritional Conditions ◽  
Research Findings

Exercise has health benefits and prevents a range of chronic diseases caused by physiological and biological changes in the whole body. Generally, the metabolic regulation of skeletal muscle through exercise is known to have a protective effect on the pathogenesis of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and cardiovascular disease (CVD). Besides this, the importance of the liver as an endocrine organ is a hot research topic. Hepatocytes also secrete many hepatokines in response to nutritional conditions and/or physical activity. In particular, certain hepatokines play a major role in the regulation of whole-body metabolic homeostasis. In this review, we summarize the recent research findings on the exercise-mediated regulation of hepatokines, including fibroblast growth factor 21, fetuin-A, angiopoietin-like protein 4, and follistatin. These hepatokines serve as molecular transducers of the metabolic benefits of physical activity in chronic metabolic diseases, including NAFLD, T2D, and CVDs, in various tissues.

scholarly journals Fat Mass and Obesity Associated (FTO) Gene and Hepatic Glucose and Lipid Metabolism

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1600 ◽  
Author(s):  
Tooru Mizuno
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Fat Mass ◽  
Metabolic Diseases ◽  
Fto Gene ◽  
Glucose And Lipid Metabolism ◽  
Common Genetic Variants ◽  
Regulation Of Metabolism ◽  
Hepatic Glucose

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed. Earlier studies have focused on the role of hypothalamic FTO in the regulation of metabolism. However, recent studies suggest that expression of hepatic FTO is regulated by metabolic signals, such as nutrients and hormones, and altered FTO levels in the liver affect glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: FXR signalling: a novel target in metabolic diseases

2021 ◽  
Vol 184 (5) ◽  
pp. R193-R205
Author(s):  
David P Sonne
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acid ◽  
Gastrointestinal Tract ◽  
Glucose Metabolism ◽  
Metabolic Diseases ◽  
Farnesoid X Receptor ◽  
Optimal Size ◽  
Lipid Digestion ◽  
Alcoholic Fatty Liver

During the last decades, it has become clear that the gastrointestinal tract plays a pivotal role in the regulation of glucose homeostasis. More than 40 hormones originate from the gastrointestinal tract and several of these impact glucose metabolism and appetite regulation. An astonishing example of the gut’s integrative role in glucose metabolism originates from investigations into bile acid biology. From primary animal studies, it has become clear that bile acids should no longer be labelled as simple detergents necessary for lipid digestion and absorption but should also be recognised as metabolic regulators implicated in lipid, glucose and energy metabolism. The nuclear farnesoid X receptor (FXR) is a part of an exquisite bile acid-sensing system that among other things ensures the optimal size of the bile acid pool. In addition, intestinal and hepatic FXR also impact the regulation of several metabolic processes such as glucose and lipid metabolism. Accordingly, natural and synthetic FXR agonists and certain FXR-regulated factors (i.e. fibroblast growth factor 19 (FGF19)) are increasingly being evaluated as treatments for metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease (and its inflammatory version, non-alcoholic steatohepatitis). Interestingly, decreased FXR activation also benefits glucose metabolism. This can be obtained by reducing bile acid absorption using bile acid sequestering agents (approved for the treatment of type 2 diabetes) or inhibitors of intestinal bile acid transporters,that is the apical sodium-dependent bile acid transporter (ASBT). This article discusses recent clinical trials that provide insights about the role of FXR-FGF19-targetted therapy for the treatment of metabolic diseases.

scholarly journals Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes

2012 ◽  
Vol 167 (4) ◽  
pp. 569-578 ◽  
Author(s):  
Francisco J Ortega ◽  
Mónica Sabater ◽  
José M Moreno-Navarrete ◽  
Neus Pueyo ◽  
Patricia Botas ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Lipid Metabolism ◽  
Inflammatory Markers ◽  
Low Grade ◽  
Model Assessment ◽  
Glucose And Lipid Metabolism ◽  
Obese Subjects

ObjectiveIncreased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.DesignWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (SI, Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19).ResultsCirculating calprotectin was significantly increased in IGT–T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin withSIwas independent of BMI and age. In fact,SItogether with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR.ConclusionThese findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.

Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes

2018 ◽  
Vol 36 (4) ◽  
pp. 322-324 ◽  
Author(s):  
Alia Hadefi ◽  
Vincent Huberty ◽  
Arnaud Lemmers ◽  
Marianna Arvanitakis ◽  
David Maggs ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bypass Surgery ◽  
Metabolic Diseases ◽  
Invasive Procedure ◽  
Diabetic Patients ◽  
Intestinal Bypass ◽  
Alcoholic Fatty Liver ◽  
Glucose Homoeostasis ◽  
Alcoholic Fatty Liver Disease

Type 2 diabetes is a pandemic disease with an incidence that has risen steadily over recent decades. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has an important role in glucose homoeostasis. Furthermore, Roux-en-Y bypass performed as bariatric surgery has shown to correct hyperglycaemia from the first postoperative days in obese diabetic patients. Therefore, on the basis of these considerations, duodenal mucosal resurfacing was studied in type 2 diabetes patients as a minimally invasive procedure that could offer an alternative treatment for these patients. Further studies, and particularly large controlled trials, are needed to determine the place of this procedure in the treatment of type 2 diabetes as well as other metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

SEX DIFFERENCES OF CARBOHYDRATE AND LIPID METABOLISM IMPAIRMENT IN RATS WITH TYPE 2 DIABETES MELLITUS

2018 ◽  
Vol 64 (2) ◽  
pp. 39-45 ◽  
Author(s):  
Nataliia Gorbenko ◽  
Oleksii Borikov ◽  
Olha Ivanova ◽  
K. V. Taran ◽  
T. S. Litvinova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Lipid Metabolism ◽  
Female Rats ◽  
Glucose And Lipid Metabolism ◽  
Carbohydrate And Lipid Metabolism ◽  
Lipid Metabolism Disorders

A sex difference of carbohydrate and lipid metabolism disorders in rats with type 2 diabetes has been studied. It was established that type 2 diabetes leads to a more pronounced deterioration in carbohydrate toleranceand insulin sensitivity in males compared to female rats, but the sex doesn’t affect basal glycemia and fructosamine levels. It was found that the increase of body weight and visceral fat in rats with type 2 diabetes is moremanifested in females than in males. It has been determined that hypertriglyceridemia is higher in diabeticmales compared to diabetic females, and the level of common lipids in the liver, both intact females and femaleswith type 2 diabetes, is lower than that of the males. The obtained results indicate a more expressive impairment of glucose and lipid metabolism in males compared to females with type 2 diabetes

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