Hepatocyte-specific fibroblast growth factor 21 overexpression ameliorates high-fat diet-induced obesity and liver steatosis in mice

Yano, Kota; Yamaguchi, Kanji; Seko, Yuya; Okishio, Shinya; Ishiba, Hiroshi; Tochiki, Nozomi; Takahashi, Aya; Kataoka, Seita; Okuda, Keiichiroh; Liu, Yu; Fujii, Hideki; Umemura, Atsushi; Moriguchi, Michihisa; Okanoue, Takeshi; Itoh, Yoshito

doi:10.1038/s41374-021-00680-9

Cited by 35 publications

(25 citation statements)

References 61 publications

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“…For example, one in vitro study showed that dehydrovomifoliol-induced FGF21 can alleviate lipid accumulation in HepG2 cells 184 . In mouse models, the overexpression of hepatocyte-specific FGF21 can ameliorate HFD-induced liver steatosis 185 . Notably, the effect of FGF21 on liver steatosis is sex-specific in obese A(y) mice, showing more beneficial effects on males with melanocortin obesity 186 .…”

Section: Fgf21 and Metabolic Diseasesmentioning

confidence: 99%

Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine

Tan¹,

Tong²,

Chen³

et al. 2023

Int. J. Biol. Sci.

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Cardiovascular and metabolic disease (CVMD) is becoming increasingly prevalent in developed and developing countries with high morbidity and mortality. In recent years, fibroblast growth factor 21 (FGF21) has attracted intensive research interest due to its purported role as a potential biomarker and critical player in CVMDs, including atherosclerosis, coronary artery disease, myocardial infarction, hypoxia/reoxygenation injury, heart failure, type 2 diabetes, obesity, and nonalcoholic steatohepatitis. This review summarizes the recent developments in investigating the role of FGF21 in CVMDs and explores the mechanism whereby FGF21 regulates the development of CVMDs. Novel molecular targets and related pathways of FGF21 (adenosine 5'-monophosphate-activated protein kinase, silent information regulator 1, autophagy-related molecules, and gut microbiota-related molecules) are highlighted in this review. Considering the poor pharmacokinetics and biophysical properties of native FGF21, the development of new generations of FGF21-based drugs has tremendous therapeutic potential. Related preclinical and clinical studies are also summarized in this review to foster clinical translation. Thus, our review provides a timely and insightful overview of the physiology, biomarker potential, molecular targets, and therapeutic potential of FGF21 in CVMDs.

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Section: Fgf21 and Metabolic Diseasesmentioning

confidence: 99%

Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine

Tan¹,

Tong²,

Chen³

et al. 2023

Int. J. Biol. Sci.

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“…Transcription factor peroxisome proliferatoractivated receptor a (PPARa) is the main mediator of different nutritional states; in fact, PPARa binding FGF21 (ID: 26291) promotor region enhances its expression (138)(139)(140). Metabolically circulating FGF-21 stimulates insulin-dependent glucose uptake in peripheral tissues, preventing excessive hyperglycemia after food intake (141)(142)(143). Interestingly, several studies also performed using transgenic mice models have shown how FGF-21 decreased sweet and alcohol intake, acting on hypothalamic neurons and regulating food intake.…”

Section: Orchestra Of Signals: Fgf-21mentioning

confidence: 99%

Chrono-communication and cardiometabolic health: The intrinsic relationship and therapeutic nutritional promises

Senesi

Ferrulli²,

Luzi³

et al. 2022

Front. Endocrinol.

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Circadian rhythm, an innate 24-h biological clock, regulates several mammalian physiological activities anticipating daily environmental variations and optimizing available energetic resources. The circadian machinery is a complex neuronal and endocrinological network primarily organized into a central clock, suprachiasmatic nucleus (SCN), and peripheral clocks. Several small molecules generate daily circadian fluctuations ensuring inter-organ communication and coordination between external stimuli, i.e., light, food, and exercise, and body metabolism. As an orchestra, this complex network can be out of tone. Circadian disruption is often associated with obesity development and, above all, with diabetes and cardiovascular disease onset. Moreover, accumulating data highlight a bidirectional relationship between circadian misalignment and cardiometabolic disease severity. Food intake abnormalities, especially timing and composition of meal, are crucial cause of circadian disruption, but evidence from preclinical and clinical studies has shown that food could represent a unique therapeutic approach to promote circadian resynchronization. In this review, we briefly summarize the structure of circadian system and discuss the role playing by different molecules [from leptin to ghrelin, incretins, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF15)] to guarantee circadian homeostasis. Based on the recent data, we discuss the innovative nutritional interventions aimed at circadian re-synchronization and, consequently, improvement of cardiometabolic health.

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“…FGF21 is a hormone involved in the regulation of lipid and glucose metabolism and its expression is regulated by a variety of physiological conditions [ 21 , 22 , 23 ]. Due to its association with obesity and liver injury, the high levels of circulating FGF21 are often linked to different dysfunctional metabolic processes [ 24 ]. About this, higher serum FGF21 levels have been also associated with worse survival in hepatocellular carcinoma (HCC) patients [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effects of Table Grape Use on Serum Levels of Omega-3 Index and Liver Function: A Randomized Controlled Clinical Trial

et al. 2022

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This clinical trial was aimed to investigate the effects of fresh table grape intake on the serum levels of the Omega-3 index, defined as the sum of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) levels. Forty consecutive healthy subjects were randomly assigned to the control group, receiving only dietary recommendations, and the grape group receiving a daily dose of 5 g of fresh table grape per kg of body weight, for 21 days. Compared with baseline, the grape treatment produced no significant difference in the serum levels of glucose, liver transaminase, and triglycerides, with the exception of cholesterol value, which was significantly reduced in both control and grape group (180.5 ± 20.32 vs. 196.1 ± 30.0 and 181.4 ± 21.9 vs. 194.3 ± 37.5, respectively). After 4 weeks from the end of grape treatment, the analysis of single fatty acids showed a significant increase in oleic acid content (14.15 ± 1.8 vs. 12.85± 1.6, p < 0.05) and a significant induction of the Omega-3 index (8.23 ± 1.9 vs. 6.09 ± 1.2, p < 0.05), associated with increased serum levels of adiponectin (24.09 ± 1.08 vs. 8.8 ± 0.7, p < 0.001). In contrast, the expression of fibroblast growth factor 21 (FGF21), a molecule associated with metabolic syndrome and liver disease, was significantly reduced (37.9 ± 6.8 vs. 107.8 ± 10.1, p < 0.001). The data suggest that the intake of fresh grape improves the Omega-3 index in the serum and exerts beneficial effects on liver function through the overexpression of adiponectin and the reduction in FGF21 levels.

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Hepatocyte-specific fibroblast growth factor 21 overexpression ameliorates high-fat diet-induced obesity and liver steatosis in mice

Cited by 35 publications

References 61 publications

Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine

Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine

Chrono-communication and cardiometabolic health: The intrinsic relationship and therapeutic nutritional promises

Beneficial Effects of Table Grape Use on Serum Levels of Omega-3 Index and Liver Function: A Randomized Controlled Clinical Trial

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