Fgf cholesterol metabolism

INTRODUCTION: Elevated fibroblast growth factor-21 (FGF-21) levels are related to carotid intima-media thickness (CIMT), a well-established marker of atherosclerosis. Acromegaly has also been linked to increased CIMT. There has been no data considering the association between FGF-21 levels and atherosclerosis in acromegaly patients. This study aimed to evaluate FGF-21 levels and CIMT in acromegalic patients in relation to atherosclerotic complications. DESIGN: Case-control study...

OBJECTIVE: Several recent studies have been undertaken into carbohydrate-restricted diets. it has not been clearly demonstrated whether diets with different proportions of energy from carbohydrate exert distinct effects on metabolism and inflammation or not. The current randomized clinical trial (RCT) has been conducted to further elucidate the effects of severe and mild carbohydrate restriction on inflammation and cardiometabolic status in adults with metabolic syndrome (MetS). METHODS: Eighty adults with metabolic syndrome were randomized to one of the four carbohydrate restricted diets: Paleolithic-based low-carbohydrate diet with calorie-counting method (PLCD-CC) (n = 20), Paleolithic-based low-carbohydrate diet with portion-control method (PLCD-PC) (n = 20), moderate-carbohydrate diet with calorie-counting method (MCD-CC) (n = 20) and moderate-carbohydrate diet with portion-control method (MCD-PC) (n = 20) for 10 weeks...

Chronic liver disease (CLD) is one of the leading causes of disability-adjusted life years in many countries. A recent understanding of nuclear bile acid receptor pathways has increased focus on the impact of crosstalk between the gut, bile acids, and liver on liver pathology. While conventionally used in cholestatic disorders and to dissolve gallstones, the discovery of bile acids' influence on the gut microbiome and human metabolism offers a unique potential for their utility in early and advanced liver diseases because of diverse etiologies...

Bile acids (BAs) are produced from cholesterol in the liver and are termed primary BAs. Primary BAs are conjugated with glycine and taurine in the liver and then released into the intestine via the gallbladder. After the deconjugation of glycine or taurine by the gut microbiome, primary BAs are converted into secondary BAs by the gut microbiome through modifications such as dehydroxylation, oxidation, and epimerization. Most BAs in the intestine are reabsorbed and transported to the liver, where both primary and secondary BAs are conjugated with glycine or taurine and rereleased into the intestine...

Hypothyroidism is often associated with elevated serum levels of total cholesterol, LDL-C and triglycerides. Thyroid hormone (TH) affects the production, clearance and transformation of cholesterol, but current research shows that thyroid-stimulating hormone (TSH) also participates in lipid metabolism independently of TH. Therefore, the mechanism of hypothyroidism-related dyslipidemia is associated with the decrease of TH and the increase of TSH levels. Some newly identified regulatory factors, such as proprotein convertase subtilisin/kexin type 9, angiogenin-like proteins and fibroblast growth factors are the underlying causes of dyslipidemia in hypothyroidism...

Fibroblast growth factor (FGF) 21 has various functions, including glucose and lipid metabolism. This cross-sectional study aimed to investigate specific conditions that might influence the functions of FGF21. 398 men who underwent a health examination were enrolled in this study. Physical and biochemical parameters and information on several lifestyle behaviors were obtained from all subjects. FGF21 levels correlated with age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and HbA1c...

BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in Abcb4-/- mice with deficiency of the hepatobiliary phospholipid transporter. METHODS: Total RNA was extracted from wild-type (WT, C57BL/6J) and Abcb4- /- (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; n = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; n = 28/group)...

Cholesterol overloading and bile acid metabolic disorders play an important role in the onset of cholesterol gallstone (CGS). Short-chain fatty acids (SCFAs) can regulate bile acid metabolism by modulating the gut microbiota. However, the role and mechanism by which sodium butyrate (NaB) targets bile acids to attenuate CGS are still unknown. In this study, continuous administration of 12 mg/day for 8 weeks was decreased the incidence of gallstones induced by lithogenic diet (LD) from 100% to 25%. NaB modulated SCFAs and improved the gut microbiota...

Common carotid intima-media thickness (IMT) represents a functional and structural marker of early, precocious, and subclinical atherosclerosis, independently from the carotid plaque. Macrophage cells, which have been detected in adipose tissue and atherosclerotic plaques, are regulated by interleukin-15 (IL-15). At the light of the conflicting results concerning the role of IL-15 in atherosclerosis, the aim of the study was to retrospectively evaluate in a population of 80 obese patients, with median age of 46 years (IQR 34-53 years), with a low rate of comorbidities but with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS), the relationship between IMT and serum concentrations of IL-15...

Background and Aims: Fibroblast growth factor 21 (FGF21), an emerging metabolic hepatokine, is associated with atherosclerosis. An interaction with sex has been described in various populations. We aimed to study whether sex modulates the relationship between FGF21 and subclinical carotid atherosclerosis in a diabetes-enriched multiethnic population of Singapore. We explore differences in intermediary mechanisms, in terms of hypertension, lipids, and inflammation, between FGF21 and atherosclerosis. Methods: We recruited 425 individuals from a single diabetes center in Singapore, and demographics, anthropometry, metabolic profile, FGF21, and carotid ultrasonography were performed...

Beneficial effects of probiotic, prebiotic and polyphenol-rich interventions on fasting lipid profiles have been reported, with changes in the gut microbiota composition believed to play an important role in lipid regulation. Primary bile acids, which are involved in the digestion of fats and cholesterol metabolism, can be converted by the gut microbiota to secondary bile acids, some species of which are less well reabsorbed and consequently may be excreted in the stool. This can lead to increased hepatic bile acid neo-synthesis, resulting in a net loss of circulating low-density lipoprotein...

BACKGROUND & AIMS: Tropifexor (TXR) is a novel nonbile acid that acts as an agonist of farnesoid X receptor (FXR). TXR is currently in Phase 2 trials for the treatment of non-alcoholic steatohepatitis (NASH). Herein, we report the impact of TXR on in a piglet model in which cholestatic liver damage and fibrosis where induced by bile duct ligation (BDL). METHODS: The piglets received BDL and TXR for 2 wk. Hepatic, portal and colonic bile acid and amino acid profiles and gut microbiome were analysed...

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) is a life-threatening complication for patients with intestinal failure who receive long-term parenteral nutrition (PN). We evaluated the effects of the farnesoid X receptor agonist tropifexor on a neonatal piglet model of IFALD fed with PN. METHODS: The piglets received PN and tropifexor for 14 days, then levels of liver enzymes, bile acid metabolism, inflammation, and intestinal barrier markers were assessed using quantitative real-time PCR...

AIMS: Fibroblast growth factor (FGF) 21, a key regulator of energy metabolism, is currently evaluated in humans for treatment of type 2 diabetes and non-alcoholic steatohepatitis. However, the effects of FGF21 on cardiovascular benefit, particularly on lipoprotein metabolism in relation to atherogenesis, remain elusive. METHODS AND RESULTS: Here, the role of FGF21 in lipoprotein metabolism in relation to atherosclerosis development was investigated by pharmacological administration of a half-life extended recombinant FGF21 protein to hypercholesterolaemic APOE*3-Leiden...

OBJECTIVES: Fibroblast growth factor 19 (FGF-19) is a metabolic regulating factor with an anti-diabetic effect. This study aimed to evaluate FGF-19 in patients with type 2 diabetes mellitus (T2DM) and its relationship with some metabolic risk factors. METHODS: In this case-control study, 80 diabetic patients and 80 non-diabetic individuals were divided into two subgroups based on body mass index (BMI): obese people (BMI≥30) and participants with normal weight (25>BMI≥18...

BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin-binding sites (FGF1△HBS ) against NAFLD. APPROACH AND RESULTS: FGF1△HBS administration was effective in 9-month-old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased...

Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism, components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. Irisin and fibroblast growth factor-21 (FGF-21), which regulate browning, and high molecular weight (HMW) adiponectin have emerged beneficial for metabolic health. The purpose of the study was to examine the effect of endurance aerobic exercise on circulating browning factor and HMW-adiponectin level in postmenopausal women...

OBJECTIVE: Cardiovascular disease is a leading cause of death worldwide. Obesity-related metabolic disorders including dyslipidemia cause impaired collateralization under ischemic conditions, thereby resulting in exacerbated cardiovascular dysfunction. Pemafibrate is a novel selective PPARα modulator, which has been reported to improve atherogenic dyslipidemia, in particular, hypertriglyceridemia and low HDL-cholesterol. Here, we investigated whether pemafibrate modulates the revascularization process in a mouse model of hindlimb ischemia...

OBJECTIVE: Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease. DESIGN: To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort). METHODS: 1506 participants that attended both the visit-1 and visit-4, separated by ≈20 years...

Compared to humans, rodents have higher synthesis of cholesterol and bile acids, and faster clearance and lower levels of serum LDL cholesterol. Paradoxically, they increase bile acid synthesis in response to bile duct ligation (BDL). Another difference is the production of hydrophilic 6-hydroxylated muricholic acids (MCAs), which may antagonize the activation of farnesoid-X-receptors, in rodents versus humans. We hypothesized that the presence of MCAs is key for many of these metabolic differences between mice and humans...