Fibroblast growth factor 21 in dairy cows: current knowledge and potential relevance

Eder, Klaus; Geßner, Denise K.; Ringseis, Robert

doi:10.1186/s40104-021-00621-y

Cited by 12 publications

(12 citation statements)

References 135 publications

(225 reference statements)

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“…FGF21 significantly increased the expression of CPT1A, PPARD, and PPARGC1A in 3T3-L1 cells [ 30 ]. Consistent with mice and humans, the primary tissue for FGF21 synthesis and secretion in dairy cows is the liver [ 27 , 29 ]. During the perinatal period, FGF21 is strongly induced.…”

Section: Discussionmentioning

confidence: 98%

“…The metabolic importance of FGF21 was evident in transgenic mice that overexpressed FGF21 and were deficient in FGF21 [ 29 , 30 ]. Mice overexpressing hepatic FGF21 showed an increased production of liver ketone bodies and an enhanced expression of key genes involved in gluconeogenesis and fatty acid oxidation [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the induction of FGF21 is required for the normal activation of liver lipid oxidation, gluconeogenesis, and ketone production in response to nutritional challenges [ 31 ]. In rodents, the reduction in liver fat content is mainly caused by increased β -oxidation of fatty acids and reduced de novo synthesis of fatty acids after exogenous FGF21 administration [ 29 ]. FGF21 or FGF21 analogues decrease the expression of diet-induced lipogenic genes, including SCD1 FASN and/or SREBF1 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

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FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling

Kong

Zhao

Tan

et al. 2022

Animals

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During the periparturient period, dairy cows suffer drastic metabolic stress because of plasma increased non-esterified fatty acids (NEFAs) that stem from a negative energy balance. Fibroblast growth factor 21 (FGF21) is a hepatokine that activates the AMP-activated protein kinase (AMPK) signaling pathway to maintain intracellular energy balance and tissue integrity via the promotion of catabolism and the inhibition of anabolic regulation. FGF21 treatment caused a 50% reduction in triglyceride (TG) content in liver in dairy cows. However, it is not clear whether FGF21 regulates lipid metabolism in bovine liver. The purpose of this study was to evaluate the influence of FGF21 on lipid metabolism via AMPK signaling in bovine hepatocytes. The hepatocytes isolated from calves were treated with different concentrations of FGF21 or co-treated with AMPK inhibitor (BML-275). Herein, the study showed that FGF21 significantly reduced TG content in a dose–response manner and promoted very-low-density lipoprotein (VLDL) secretion via an up-regulation of the proteins (ApoB 100, ApoE and MTTP) involved in VLDL secretion. Otherwise, the genes associated with lipid transport (LDLR and CD36) and lipid oxidation (PPARGC1A, ACOX1 and CPT1A), were up-regulated following FGF21 treatment. Moreover, FGF21 treatment inhibited lipogenesis via SREBF1, ACACA, FASN and ACLY inhibition. After being co-treated with the AMPK inhibitor, FGF21-induced changes were reversed in some genes. In conclusion, these results indicate that FGF21 adaptively regulates energy metabolism for a negative impact on lipogenesis, strengthens lipid oxidation, and inhibited lipid transportation via AMPK signaling in bovine hepatocytes. The present data suggest the possibility that FGF21 has potential value in alleviating perinatal metabolic diseases in dairy cows, and specific research in vivo should be studied in more detail.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling

Kong

Zhao

Tan

et al. 2022

Animals

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“…tissue cross talk) by inducing expression of secreted signaling molecules. One example of this effect is the hepatokine fibroblast growth factor 21 (FGF21), a signaling molecule whose transcription is controlled by PPARα in the liver and after secretion into the circulation can affect adipose tissue metabolism (Eder et al 2021). Adipokines such as adiponectin represent another example of a protein under control of TF (e.g.…”

Section: Transcription-factor Network and Nutrigenomicsmentioning

confidence: 99%

Nutrigenomics in livestock: potential role in physiological regulation and practical applications

Loor

2022

Anim. Prod. Sci.

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The relationship among nutrition, health, and productivity of livestock is a continuously changing interaction between environment and physiology. As such, understanding how the physiological system is able to adapt to the type and amount of nutrients consumed is central to our ability to care for and manage livestock. Recognition that cells possess proteins with the ability to ‘sense’ and trigger a cascade of biological events in response to nutrient availability is at the core of nutritional genomics (or nutrigenomics) as a field of science. Nutrigenomics is generally defined as the study of the genome-wide influence of nutrition. Certain transcriptional regulators can interact with nutrients and cause large-scale alterations in gene expression, metabolic and signaling pathways, and ultimately tissue function. The advent of high-throughput technologies to study an animal’s microbiome, genome, transcriptome, proteome, and metabolome (i.e. ‘omics’ tools) has been instrumental in moving the field of nutrigenomics forward. Available data from studies with livestock species using targeted or untargeted molecular methods underscore the existence of networks of multiple transcriptional regulators at play in controlling nutrigenomics responses. Fatty acids, amino acids, trace nutrients, and level of feed and energy intake have the strongest reported nutrigenomics potential. An important goal for applying nutrigenomics at the animal level is to uncover key molecular players involved in the physiological adaptations to changes in nutrient supply and environmental conditions.

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“…Moreover, application of FGF21 improved the profile of plasma lipids (decline of low-density lipoprotein cholesterol and triacylglycerols, elevation of high-density lipoprotein cholesterol). While the function of FGF21 in pathologic rodent models has been extensively studied, knowledge about the function of FGF21 in dairy cows is limited, despite existing reports about the factors underlying induction of FGF21 expression in dairy cows [29].…”

Section: Introductionmentioning

confidence: 99%

Performance and Metabolic, Inflammatory, and Oxidative Stress-Related Parameters in Early Lactating Dairy Cows with High and Low Hepatic FGF21 Expression

Geßner

Sandrock

Most

et al. 2022

Animals

Self Cite

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Induction of FGF21 expression in the liver and a significant increase in plasma FGF21 concentration have been demonstrated in cows during early lactation, but knowledge about the function of FGF21 in dairy cows remains limited. In order to improve the understanding of the physiological role of FGF21 in dairy cows, the present study aimed to investigate differences in metabolic pathways between dairy cows with high and low hepatic expression of FGF21 at week 1 of lactation (n = 8/group) by liver transcriptomics, targeted plasma metabolomics, and analysis of inflammatory and oxidative stress-related parameters. Dry matter intake, energy balance, milk yield, and energy-corrected milk yield at days 8–14 postpartum did not differ between cows with high and low hepatic FGF21 expression. However, cows with high FGF21 expression showed an upregulation of genes involved in endoplasmic reticulum stress, inflammation, and nuclear factor E2-related factor 2 (Nrf2)-dependent cytoprotection compared to cows with low FGF21 expression at week 1 postpartum (p < 0.05). Concentrations of important antioxidants (tocopherols, β-carotene, and glutathione) in the liver and plasma, trolox equivalent antioxidant capacity in plasma, concentrations of oxidative stress-related compounds (thiobarbituric acid-reactive substances and protein carbonyls), and levels of most acute phase proteins at week 1 postpartum did not differ between cows with high or low FGF21 expression. Moreover, among a total of >200 metabolites assayed in the plasma, concentrations of only 7 metabolites were different between cows with high or low FGF21 expression (p < 0.05). Overall, the results showed that cows with high and low FGF21 hepatic expression had only moderate differences in metabolism, but FGF21 might be important in the adaptation of dairy cows to stress conditions during early lactation.

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Fibroblast growth factor 21 in dairy cows: current knowledge and potential relevance

Cited by 12 publications

References 135 publications

FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling

FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling

Nutrigenomics in livestock: potential role in physiological regulation and practical applications

Performance and Metabolic, Inflammatory, and Oxidative Stress-Related Parameters in Early Lactating Dairy Cows with High and Low Hepatic FGF21 Expression

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