Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation and Chronic Diseases

Zhang, Fangfang; Yu, Lechu; Lin, Xiufei; Peng, Cheng; He, Luqing; Li, Xiaokun; Lu, Xuemian; Tan, Yi; Yang, Hong; Cai, Lu; Zhang, Chi

doi:10.1210/me.2015-1155

Cited by 110 publications

(124 citation statements)

References 109 publications

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“…For example, ghrelin (Tschöp et al, 2000), corticosterone (Dallman et al, 1999), and FGF21 (Zhang et al, 2015) are all significantly elevated during food deprivation. Interestingly, all of these hormones inhibit the reproductive neuroendocrine axis (Barreiro and Tena-Sempere, 2004; Kinsey-Jones et al, 2009; Owen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance

Heppner

Baquero

Lindsley

et al. 2017

eNeuro

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Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action. Using ovariectomized mice, we found that GLP-producing fibers come in close apposition with ARC Kiss1 neurons; these neurons also contain Glp1r mRNA. Electrophysiological recordings revealed that liraglutide (a long-acting GLP-1R agonist) increased action potential firing and caused a direct membrane depolarization of ARC Kiss1 cells in brain slices. We determined that brainstem preproglucagon mRNA is decreased after a 48-h fast in mice, a negative energy state in which ARC Kiss1 expression and downstream GnRH/luteinizing hormone (LH) release are potently suppressed. However, activation of GLP-1R signaling in fasted mice with liraglutide was not sufficient to prevent LH inhibition. Furthermore, chronic central infusions of the GLP-1R antagonist, exendin(9–39), in ad libitum–fed mice did not alter ARC Kiss1 mRNA or plasma LH. As a whole, these data identify a novel interaction of the GLP-1 system with ARC Kiss1 neurons but indicate that CNS GLP-1R signaling alone is not critical for the maintenance of LH during fasting or normal feeding.

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Section: Discussionmentioning

confidence: 99%

GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance

Heppner

Baquero

Lindsley

et al. 2017

eNeuro

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“…In vitro and animal studies revealed that it stimulates lipolysis in the white adipose tissue and ketogenesis in the liver, improves insulin signaling and hepatic glycogen production, and reduces gluconeogenesis. In addition, FGF-21 can ameliorate dyslipidemia [58, 65] and enhance the “browning” of the white adipose tissue. FGF-21 serum levels increase with hepatic fat content, independently of obesity development, and visceral fat as well as with hepatic or adipocyte insulin resistance.…”

Section: The Role Of Adipocytokines In the Pathogenesis Of Metabolic mentioning

confidence: 99%

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

Bussler¹,

Penke²,

Flemming³

et al. 2017

Horm Res Paediatr

112

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Metabolic syndrome (MetS) is recognized as an escalating major health risk in adults as well as in children and adolescents. Its prevalence ranges from 6 to 39% depending on the applied definition criteria. To date, there is no consensus on a MetS definition for children and adolescents. However, most authors agree on essential components such as glucose intolerance, central obesity, hypertension, and dyslipidemia; each representing a risk for cardiovascular disease. Recently, associations between MetS and non-alcoholic fatty liver disease, hyperuricemia, and sleep disturbances have emerged. Biomarkers like adipocytokines are a subject of current research as they are implicated in the pathogenesis of the MetS. Epigenetics and gestational programming, especially the role of microRNA, comprise a novel, rapidly developing and promising research focus on the topic of MetS. MicroRNAs are increasingly valued for potential roles in the diagnosis, stratification, and therapeutics of MetS. Early detection of risk factors, screening for metabolic disturbances, and the identification of new therapies are major aims to reduce morbidity and mortality related to MetS. Dietary modification and physical activity are currently the only adopted treatment approaches. Pharmacological therapies and bariatric surgery are still contradictory and, therefore, are only recommended in selected high-risk cases.

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“…ChREBP is upregulated during adipocyte differentiation and, thus, may be involved in the induction of FGF21 in these cells [37]. In adipocytes, FGF21 is induced by feeding in a PPARγ-dependent manner [38]. PPARγ agonists, such as the thiazolidinedione drugs, also induce FGF21 gene expression in white adipose tissue and isolated adipocytes [28,39,40].…”

Section: Body Of Review Regulation By Starvation and Overnutritionmentioning

confidence: 99%

The regulation of FGF21 gene expression by metabolic factors and nutrients

Erickson

Moreau

2016

Hormone Molecular Biology and Clinical Investigation

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Fibroblast growth factor 21 (FGF21) gene expression is altered by a wide array of physiological, metabolic, and environmental factors. Among dietary factors, high dextrose, low protein, methionine restriction, short-chain fatty acids (butyric acid and lipoic acid), and all-trans-retinoic acid were repeatedly shown to induce FGF21 expression and circulating levels. These effects are usually more pronounced in liver or isolated hepatocytes than in adipose tissue or isolated fat cells. Although peroxisome proliferator-activated receptor α (PPARα) is a key mediator of hepatic FGF21 expression and function, including the regulation of gluconeogenesis, ketogenesis, torpor, and growth inhibition, there is increasing evidence of PPARα-independent transactivation of the FGF21 gene by dietary molecules. FGF21 expression is believed to follow the circadian rhythm and be placed under the control of first order clock-controlled transcription factors, retinoic acid receptor-related orphan receptors (RORs) and nuclear receptors subfamily 1 group D (REV-ERBs), with FGF21 rhythm being anti-phase to REV-ERBs. Key metabolic hormones such as glucagon, insulin, and thyroid hormone have presumed or clearly demonstrated roles in regulating FGF21 transcription and secretion. The control of the FGF21 gene by glucagon and insulin appears more complex than first anticipated. Some discrepancies are noted and will need continued studies. The complexity in assessing the significance of FGF21 gene expression resides in the difficulty to ascertain (i) when transcription results in local or systemic increase of FGF21 protein; (ii) if FGF21 is among the first or second order genes upregulated by physiological, metabolic, and environmental stimuli, or merely an epiphenomenon; and (iii) whether FGF21 may have some adverse effects alongside beneficial outcomes.

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Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation and Chronic Diseases

Cited by 110 publications

References 109 publications

GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance

GLP-1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

The regulation of FGF21 gene expression by metabolic factors and nutrients

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