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Mariya Markova, Olga Pivovarova, Silke Hornemann, Stephanie Sucher, Turid Frahnow, Katrin Wegner, Jürgen Machann, Klaus Jürgen Petzke, Johannes Hierholzer, Ralf Lichtinghagen, Christian Herder, Maren Carstensen-Kirberg, Michael Roden, Natalia Rudovich, Susanne Klaus, Ralph Thomann, Rosemarie Schneeweiss, Sascha Rohn, Andreas F H Pfeiffer
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat but may induce insulin resistance. We investigated the effects of diets high in animal protein vs plant protein, which differ in levels of methionine and BCAA, in subjects with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue...
October 17, 2016: Gastroenterology
David Holmes
No abstract text is available yet for this article.
October 17, 2016: Nature Reviews. Endocrinology
Christian Faul
Fibroblast growth factors (FGF) are mitogenic signal mediators that induce cell proliferation and survival. Although cardiac myocytes are post-mitotic, they have been shown to be able to respond to local and circulating FGFs. While precise molecular mechanisms are not well characterized, some FGF family members have been shown to induce cardiac remodeling under physiologic conditions by mediating hypertrophic growth in cardiac myocytes and by promoting angiogenesis, both events leading to increased cardiac function and output...
October 7, 2016: Bone
Kotaro Sakamoto, Yayoi Kawata, Yasushi Masuda, Tadashi Umemoto, Takashi Ito, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki, Hiroshi Inooka
Fibroblast growth factor receptor-1c (FGFR1c)/βKlotho (KLB) complex is a receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows anti-obesity and anti-diabetic effects upon peripheral administration. Here, we report the development of an artificial peptide agonist to the FGFR1c/KLB heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered from random peptide T7 phage display and selectively bound to the FGFR1c/KLB complex, but not to FGFR1c and KLB individually...
October 4, 2016: Biochemical and Biophysical Research Communications
Junling Fu, Cong Hou, Lujiao Li, Dan Feng, Ge Li, Mingyao Li, Changhong Li, Shan Gao, Ming Li
BACKGROUND: Betatrophin has been recently reported to play a role in glucose homeostasis by inducing beta-cell proliferation in mice. However, studies in human are inconsistent. As a nutritionally-regulated liver-enriched factor, we hypothesize that betatrophin might be regulated by vitamin D, and ignorance of vitamin D status may explain the discrepancy in previous human studies. The aims of this study were to assess the association between circulating betatrophin and glucose homeostasis as well as other cardiometabolic variables in a cohort of youths at risk for metabolic syndrome and test the possible influence of vitamin D status on the association...
October 6, 2016: Cardiovascular Diabetology
Veronika Šrámková, Lenka Rossmeislová, Eva Krauzová, Jana Kračmerová, Michal Koc, Dominique Langin, Vladimír Štich, Michaela Šiklová
CONTEXT: Beneficial metabolic effects of calorie restriction found in the early stage of hypocalorie diets may be caused by the modulation of metabolic and endocrine function of adipose tissue. OBJECTIVE: To compare metabolic and inflammation-related characteristics of subcutaneous adipose tissue (SAAT) in the early (2 days) and later (28 days) phase of VLCD. Design, Setting, Intervention and Patients: 17 moderately obese premenopausal women followed 800 kcal/d VLCD for 28 days...
October 7, 2016: Journal of Clinical Endocrinology and Metabolism
Justin D Schumacher, Grace L Guo
Fibroblast growth factors (FGFs) are a family of growth factors critically involved in developmental, physiological, and pathological processes, including embryogenesis, angiogenesis, wound healing, and endocrine functions. In the liver, several FGFs are produced basally by hepatocytes and hepatic stellate cells (HSCs). Upon insult to the liver, expression of FGFs in HSCs is greatly upregulated, stimulating hepatocyte regeneration and growth. Various FGF isoforms have also been shown to directly induce HSC proliferation and activation thereby enabling autocrine and paracrine regulation of HSC function...
2016: BioMed Research International
Samantha M Solon-Biet, Victoria C Cogger, Tamara Pulpitel, Marika Heblinski, Devin Wahl, Aisling C McMahon, Alessandra Warren, Jessica Durrant-Whyte, Kirsty A Walters, James R Krycer, Fleur Ponton, Rahul Gokarn, Jibran A Wali, Kari Ruohonen, Arthur D Conigrave, David E James, David Raubenheimer, Christopher D Morrison, David G Le Couteur, Stephen J Simpson
Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content...
October 11, 2016: Cell Metabolism
Min Ye, Weiqin Lu, Xiaojie Wang, Cong Wang, James L Abbruzzese, Guang Liang, Xiaokun Li, Yongde Luo
The anti-obese and anti-diabetic FGF21 regulates lipid metabolism and energy homeostasis by targeting the betaKlotho-FGFR1 binary complex in adipose tissue adipocytes. Since lipid droplet is the organelle responsible for storing lipid energy in adipocytes, it is the plausible target of FGF21 action. However, the impact of the FGF21-betaKlotho-FGFR1 signaling pathway on the functions of the lipid droplet is not clearly understood. Using our mouse models of adipocyte-specific FGFR1 ablation and hepatic overexpression of FGF21 with diet-induced obesity established previously, we analyzed the alterations of the pathways involved in energy and substrate metabolism that is attributable to the dynamic functions of the lipid droplet...
October 3, 2016: Endocrinology
Joaquim Fernández-Solà, Ana Planavila Porta
High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis...
September 29, 2016: International Journal of Molecular Sciences
Miguel Angel Sánchez-Garrido, Kirk M Habegger, Christoffer Clemmensen, Cassie Holleman, Timo D Müller, Diego Perez-Tilve, Pengyun Li, Archita S Agrawal, Brian Finan, Daniel J Drucker, Matthias H Tschöp, Richard D DiMarchi, Alexei Kharitonenkov
OBJECTIVE: Fibroblast activation protein (FAP) is a serine protease belonging to a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported to regulate degradation of FGF21, a potent metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. METHODS: To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling...
October 2016: Molecular Metabolism
Christopher D Morrison, Zheng Hao, Michael B Mumphrey, R Leigh Townsend, Heike Münzberg, Jianping Ye, Hans-Rudolf Berthoud
OBJECTIVE: The mechanisms by which bariatric surgeries so effectively and lastingly reduce body weight and normalize metabolic dysfunction are not well understood. Fibroblast growth fator-21 (FGF21) is a key regulator of metabolism and is currently considered for treatment of obesity. Although elevated by acute food deprivation, it is downregulated after weight loss induced by chronic calorie restriction but not after Roux-en-Y gastric bypass surgery. Therefore, the goal of the present study was to assess the role of FGF21-signaling in the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB)...
October 2016: Molecular Metabolism
Annabel Y Minard, Shi-Xiong Tan, Pengyi Yang, Daniel J Fazakerley, Westa Domanova, Benjamin L Parker, Sean J Humphrey, Raja Jothi, Jacqueline Stöckli, David E James
FGF21 improves the metabolic profile of obese animals through its actions on adipocytes. To elucidate the signaling network responsible for mediating these effects, we quantified dynamic changes in the adipocyte phosphoproteome following acute exposure to FGF21. FGF21 regulated a network of 821 phosphosites on 542 proteins. A major FGF21-regulated signaling node was mTORC1/S6K. In contrast to insulin, FGF21 activated mTORC1 via MAPK rather than through the canonical PI3K/AKT pathway. Activation of mTORC1/S6K by FGF21 was surprising because this is thought to contribute to deleterious metabolic effects such as obesity and insulin resistance...
September 27, 2016: Cell Reports
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
Fibroblast growth factor 21 (FGF21) has a significant role in the regulation of energy metabolism, e.g., in the control of systemic glucose and lipid metabolism. For instance, FGF21 enhances insulin sensitivity, increases glucose uptake, and thus can decrease serum hyperglycemia, while it also increases lipid oxidation and inhibits lipogenesis. AMP-activated protein kinase (AMPK) is a tissue energy sensor involved in maintaining the energy balance and tissue integrity. It is known that AMPK signaling generates an energy metabolic profile which displays a remarkable overlap with that of FGF21...
September 27, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Satish Sen, Hélène Raingard, Stéphanie Dumont, Andries Kalsbeek, Patrick Vuillez, Etienne Challet
Restricted feeding during the resting period causes pronounced shifts in a number of peripheral clocks, but not the central clock in the suprachiasmatic nucleus (SCN). By contrast, daily caloric restriction impacts also the light-entrained SCN clock, as indicated by shifted oscillations of clock (PER1) and clock-controlled (vasopressin) proteins. To determine if these SCN changes are due to the metabolic or timing cues of the restricted feeding, mice were challenged with an ultradian 6-meals schedule (1 food access every 4 h) to abolish the daily periodicity of feeding...
September 26, 2016: Chronobiology International
Qing Li, Yuan Zhang, Ding Ding, Yunou Yang, Qian Chen, Dongfang Su, Xuechen Chen, Wenqi Yang, Jian Qiu, Wenhua Ling
OBJECTIVES: Epidemiological studies have shown that serum fibroblast growth factor 21 (FGF21) levels were elevated in obesity and its related metabolic disorders. This prospective study assessed whether there was an independent association of serum FGF21 levels with all-cause and cardiovascular disease (CVD) mortality among patients with coronary artery disease (CAD). METHODS: A prospective cohort study of 1,668 CAD patients was conducted. Their serum FGF21 levels were measured with enzyme-linked immunosorbent assay kits...
September 23, 2016: Journal of Clinical Endocrinology and Metabolism
Ruey-Hsing Chou, Po-Hsun Huang, Chien-Yi Hsu, Chun-Chin Chang, Hsin-Bang Leu, Chin-Chou Huang, Jaw-Wen Chen, Shing-Jong Lin
Fibroblast growth factor 21 (FGF21), a polypeptide ligand promoted glucose homeostasis and lipids metabolism, was recently reported to attenuate cardiac hypertrophy. The aim of this study was to investigate the impact of FGF21 in diastolic heart failure. Subjects admitted for coronary angiogram were screened for heart failure, and those with left ventricular (LV) ejection fraction < 45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria...
2016: Scientific Reports
S G Vienberg, S H Jacobsen, D Worm, L E Hvolris, L Naver, T Almdal, D L Hansen, B S Wulff, T R Clausen, S Madsbad, J J Holst, B Andersen
OBJECTIVE: The positive metabolic outcome of Roux-en-Y gastric bypass (RYGB) surgery may involve fibroblast growth factor 21 (FGF21), in both the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal. DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Eight obese, nondiabetic patients underwent RYGB...
September 21, 2016: Clinical Endocrinology
Sylvie Casteras, Aya Abdul-Wahed, Maud Soty, Fanny Vulin, Hervé Guillou, Mélanie Campana, Hervé Le Stunff, Luciano Pirola, Fabienne Rajas, Gilles Mithieux, Amandine Gautier-Stein
AIMS/HYPOTHESIS: Despite the strong correlation between non-alcoholic fatty liver disease and insulin resistance, hepatic steatosis is associated with greater whole-body insulin sensitivity in several models. We previously reported that the inhibition of hepatic glucose production (HGP) protects against the development of obesity and diabetes despite severe steatosis, thanks to the secretion of specific hepatokines such as fibroblast growth factor 21 (FGF21) and angiopoietin-related growth factor...
September 9, 2016: Diabetologia
Laura E Downing, Bradley S Ferguson, Kelvin Rodriguez, Marie-Louise Ricketts
SCOPE: Histone deacetylases (HDACs) have emerged as epigenetic regulators of risk factors associated with the metabolic syndrome (MetS), and certain botanical extracts have proven to be potent HDAC inhibitors. Understanding the role of dietary procyanidins in HDAC inhibition is important in exploring the therapeutic potential of natural products. METHODS: C57BL/6 mice were gavaged with vehicle (water) or grape seed procyanidin extract (GSPE, 250 mg/kg) and terminated 14 hours later...
September 14, 2016: Molecular Nutrition & Food Research
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