Fibroblast growth factor 21 (FGF-21), a novel metabolic factor in obesity and fasting metabolism, has been shown to be regulated by supraphysiological levels of free fatty acids (FFAs) under hyperinsulinemic conditions. Interestingly, it is still unclear whether the observed effects of FFAs on FGF-21 are relevant under physiological conditions, and the relative functions of FFAs and insulin within this context also need to be determined. Fourteen healthy men were studied in a randomized controlled crossover trial (RCT) using lipid heparin infusion (LHI) at a dose inducing physiological elevations of FFAs vs. saline heparin infusion. In a second randomized controlled trial, FGF-21 was analyzed in 14 patients with type 1 diabetes (6 men, 8 women) during continuous insulin supply vs. discontinued insulin infusion and subsequently increased lipolysis and ketosis. Circulating FGF-21 increased during physiologically elevated FFAs induced by LHI, which was accompanied by mild hyperinsulinemia. Interestingly, a mild elevation of FFAs resulting from complete insulin deficiency also increased FGF-21 levels. These results from two independent human RCTs suggest that FFAs increase circulating FGF-21, while insulin is only of minor importance under physiological conditions. This mechanism might explain the apparent paradox of increased FGF-21 levels in obesity, insulin resistance, and starvation.
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http://dx.doi.org/10.1152/ajpendo.00020.2010 | DOI Listing |
J Agric Food Chem
January 2025
College of Food Science and Engineering, Northwest A&F University, Yangling, 712100 Shaanxi, China.
Norvaline is a nonproteinogenic amino acid and an important food ingredient supplement for healthy food. In this study, dl-norvaline administration reduced body weight by more than 40% and improved glucose metabolism and energy metabolism in obese mice induced by a high-fat diet (HFD). Combination analysis of microbiome and metabolomics showed that dl-norvaline supplementation regulated gut bacteria structure, such as increasing beneficial bacteria (, , , , , , , and ) and decreasing harmful bacteria (, , , , , and ) and modulated the metabolites involved in arachidonic acid metabolism, thus further promoting short-chain fatty acid production and improving gut barrier, thereby inflammatory responses and oxidative stress were ameliorated.
View Article and Find Full Text PDFNon-alcoholic fatty liver disease (NAFLD) is a chronic condition characterized by hepatic steatosis in the absence of significant alcohol consumption and is increasingly recognized as the hepatic manifestation of metabolic syndrome (MetS). This review aims to explore the molecular mechanisms underlying the interaction between NAFLD, insulin resistance (IR), and MetS, with a focus on identifying therapeutic targets. A comprehensive review of existing literature on NAFLD, IR, and MetS was conducted.
View Article and Find Full Text PDFEndocr Metab Immune Disord Drug Targets
January 2025
Department of Medicine, Hualien Armed Forces General Hospital, Hualien City, Taiwan.
Background: Plasma AST and ALT may reflect the nonalcoholic fatty liver disease (NAFLD) severity and have been associated with the risk of MetS in middle- or old-aged individuals.
Aims: This study aimed to examine the associations of plasma hepatic aspartate and alanine transaminases (AST and ALT) levels with incident metabolic syndrome (MetS) in young adults, which have not been verified before.
Objective: The goal of this study was to identify the association between plasma hepatic transaminases and the incidence of new-onset MetS among young adults.
Endocr Metab Immune Disord Drug Targets
January 2025
Department of Medicine, Hualien Armed Forces General Hospital, Hualien City, Taiwan.
Background: Hepatic inflammation, e.g., Nonalcoholic Fatty Liver Diseases (NAFLD) and the severe form of steatohepatitis (NASH), has been associated with a higher risk of MetS in the general population.
View Article and Find Full Text PDFJ Gastroenterol Hepatol
January 2025
Department of Oncology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Background: Clonorchis sinensis infection is an important risk factor for intrahepatic cholangiocarcinoma (ICC). C. sinensis positive (C.
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