The relationship between Fibroblast Growth Factor-21 and characteristic parameters related to energy balance in dairy cows

Negative energy balance (NEB) is a common pathological foundation of fatty liver and ketosis. Liver and fat tissue are the major organs of lipid metabolism, which is also a key metabolic pathway that regulates NEB development during the perinatal period. Fibroblast growth factor-21 (FGF-21) is a protein hormone that plays an important role in adipose lipid metabolism and liver gluconeogenesis. Our aim was to investigate the effects of exogenous FGF-21 on characteristic parameters related to energy balance in dairy cows. Ten non-pregnant, non-lactating Holstein-Friesian dairy cows were randomly allocated into two groups. The interventions were exogenous FGF-21 injection group received 1 ug/kg BW (body weight) of recombinant bovine FGF-21 by intravenous injection, and control group received physiological saline injections by intravenous injection. In comparison to saline injections, intravenous injections of FGF-21 either increased or tended to increase concentrations of FGF-21 (p < 0.05), BHBA (p < 0.05), adiponectin, leptin and HDL-C. FGF-21 injections decreased or tended to decrease concentrations of insulin, glucose, glucagon (p < 0.05), ALT/GPT (p < 0.05), AST/GOT (p < 0.05), urate, creatinine (p < 0.05), BUN, triglyceride (p < 0.05), T-CHO and LDL-C (p < 0.05). The results indicate that FGF-21 has only negative effects on the metabolites and metabolic hormones related to NEB in serum of dairy cows, but it has more beneficial effects on prominent adipokines, liver function index, renal function index, lipoprotein profiles related to the pathological changes that occurred in NEB.

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

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00621-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Klaus Eder ◽

Denise K. Gessner ◽

Robert Ringseis

Keyword(s):

Growth Factor ◽

Energy Balance ◽

Dairy Cows ◽

Fibroblast Growth Factor ◽

Negative Energy ◽

Stress Conditions ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Fgf21 Expression

AbstractFibroblast growth factor 21 (FGF21) has been identified as an important regulator of carbohydrate and lipid metabolism, which plays an important role for metabolic regulation, particularly under conditions of energy deprivation or stress conditions. Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation. It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation. This finding suggests that FGF21 might exert similar functions in dairy cows than in other species, such as mice or humans. However, the role of FGF21 in dairy cows has been less investigated so far. Following a brief summary of the previous findings about the function of FGF21 in humans and mice, the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows. The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows. In the second part, the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed. In the third part, findings of exogenous FGF21 application on metabolism in dairy cows are reported. Finally, the potential relevance of FGF21 in dairy cows is discussed. It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows. However, further studies are needed for a better understanding of the functions of FGF21 in dairy cows.

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Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. II. Pharmacokinetics, whole-animal performance, and lipid metabolism

Journal of Dairy Science ◽

10.3168/jds.2019-16696 ◽

2019 ◽

Vol 102 (12) ◽

pp. 11597-11608 ◽

Cited By ~ 2

Author(s):

L.S. Caixeta ◽

S.L. Giesy ◽

C.S. Krumm ◽

J.W. Perfield ◽

A. Butterfield ◽

...

Keyword(s):

Lipid Metabolism ◽

Growth Factor ◽

Dairy Cows ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Animal Performance ◽

Lactating Dairy Cows

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The relationship of circulating fibroblast growth factor 21 levels with incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis

Atherosclerosis ◽

10.1016/j.atherosclerosis.2017.12.026 ◽

2018 ◽

Vol 269 ◽

pp. 86-91 ◽

Cited By ~ 5

Author(s):

Tsz Him Hui ◽

Robyn L. McClelland ◽

Matthew A. Allison ◽

Carlos J. Rodriguez ◽

Richard A. Kronmal ◽

...

Keyword(s):

Atrial Fibrillation ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Ethnic Study ◽

Relationship Of ◽

The Relationship

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The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study

Diabetologia ◽

10.1007/s00125-014-3458-7 ◽

2014 ◽

Vol 58 (3) ◽

pp. 464-473 ◽

Cited By ~ 46

Author(s):

Kwok-Leung Ong ◽

Andrzej S. Januszewski ◽

Rachel O’Connell ◽

Alicia J. Jenkins ◽

Aimin Xu ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Cardiovascular Outcome ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Relationship Of ◽

The Relationship ◽

Fenofibrate Intervention

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Transient postprandial increase in intact circulating fibroblast growth factor-21 levels after Roux-en-Y gastric bypass: a randomized controlled clinical trial

PeerJ ◽

10.7717/peerj.11174 ◽

2021 ◽

Vol 9 ◽

pp. e11174

Author(s):

Mette S. Nielsen ◽

Susanna Søberg ◽

Julie B. Schmidt ◽

Anne Chenchar ◽

Anders Sjödin ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Growth Factor ◽

Energy Balance ◽

Fibroblast Growth Factor ◽

Negative Energy ◽

Negative Energy Balance ◽

Fibroblast Growth Factor 21 ◽

Control Group ◽

Fibroblast Growth

Background Despite a consistent link between obesity and increased circulating levels of fibroblast growth factor-21 (FGF21), the effect of weight-loss interventions on FGF21 is not clear. We aimed to determine the short- and long-term effects of Roux-en-Y gastric bypass (RYGB) on intact plasma FGF21 levels and to test the hypothesis that RYGB, but not diet-induced weight loss, increases fasting and postprandial responses of FGF21. Method Twenty-eight participants with obesity followed a low-calorie diet for 11 weeks. The 28 participants were randomized to undergo RYGB surgery at week 8 (RYGB group, n = 14), or to a control group scheduled for surgery at week 12 (n = 14). Fasting levels of intact, biologically active FGF21 (amino acids 1-181) and its postprandial responses to a mixed meal were assessed at week 7 and 11, and 78 weeks (18 months) after RYGB. Results At week 11 (3 weeks after RYGB), postprandial responses of intact FGF21 were enhanced in participants undergoing surgery at week 8 (change from week 7 to 11: P = 0.02), whereas no change was found in non-operated control participants in similar negative energy balance (change from week 7 to 11: P = 0.81). However, no between-group difference was found (P = 0.27 for the group-week-time interaction). Fasting, as well as postprandial responses in intact FGF21, were unchanged 18 months after RYGB when both the RYGB and control group were collapsed together (change from week 7 to 78 weeks after RYGB: P = 0.17). Conclusion Postprandial intact FGF21 levels were enhanced acutely after RYGB whereas no signs of sustained changes were found 18 months after surgery. When comparing the acute effect of RYGB with controls in similar negative energy balance, we failed to detect any significant differences between groups, probably due to the small sample size and large inter-individual variations, especially in response to surgery.

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Increased Responses to the Actions of Fibroblast Growth Factor 21 on Energy Balance and Body Weight in a Seasonal Model of Adiposity

Journal of Neuroendocrinology ◽

10.1111/j.1365-2826.2012.02383.x ◽

2013 ◽

Vol 25 (2) ◽

pp. 180-189 ◽

Cited By ~ 23

Author(s):

M. Murphy ◽

R. Samms ◽

A. Warner ◽

M. Bolborea ◽

P. Barrett ◽

...

Keyword(s):

Body Weight ◽

Growth Factor ◽

Energy Balance ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Seasonal Model

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Sex Modifies the Association of Fibroblast Growth Factor 21 With Subclinical Carotid Atherosclerosis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.627691 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yingjie Chee ◽

Grace Lx Toh ◽

Chien Joo Lim ◽

Liuh Ling Goh ◽

Rinkoo Dalan

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Carotid Atherosclerosis ◽

Subclinical Atherosclerosis ◽

Density Lipoprotein ◽

Population Based ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

The Relationship ◽

Interaction Test

Background and Aims: Fibroblast growth factor 21 (FGF21), an emerging metabolic hepatokine, is associated with atherosclerosis. An interaction with sex has been described in various populations. We aimed to study whether sex modulates the relationship between FGF21 and subclinical carotid atherosclerosis in a diabetes-enriched multiethnic population of Singapore. We explore differences in intermediary mechanisms, in terms of hypertension, lipids, and inflammation, between FGF21 and atherosclerosis.Methods: We recruited 425 individuals from a single diabetes center in Singapore, and demographics, anthropometry, metabolic profile, FGF21, and carotid ultrasonography were performed. Multivariable logistic regression models were used to study the association between subclinical atherosclerosis and FGF21 adjusting for age, ethnicity, body mass index (BMI), hemoglobin A1c (HbA1c), systolic and diastolic blood pressures, and low-density lipoprotein (LDL)-cholesterol separately for males and females as two groups after an interaction test.Results: An interaction test assessing interaction by sex on the relationship between subclinical atherosclerosis and FGF21 showed a significant interaction with sex (Pinteraction = 0.033). In the female subgroup, significant independent associations of standardized lnFGF21 with subclinical atherosclerosis were seen, with 1 SD increment in lnFGF21 being associated with 1.48-fold (95% CI: 1.03, 2.12; p = 0.036) increase in risk. In the male subgroup, the association of subclinical atherosclerosis with standardized lnFGF21 was not significant [odds ratio (OR) (95% CI): 0.90 (0.63, 1.28); p = 0.553]. We found sex interactions with pulse pressure being significantly associated in females only and triglycerides and C-reactive protein being associated with males only.Conclusion: FGF21 is positively associated with subclinical carotid atherosclerosis in women, but not in men. The sex–racial patterns in the mechanisms by which FGF21 causes subclinical atherosclerosis needs to be explored in larger population-based studies and mechanistically studied in greater detail.

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PSXIII-41 Fibroblast growth factor 21 promotes lipid oxidation and transportation while inhibits lipogenesis via AMP-activated protein kinase signaling pathway in bovine hepatocytes

Journal of Animal Science ◽

10.1093/jas/skz258.734 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 368-368

Author(s):

Jianguo Wang ◽

Xiaoyan Zhu ◽

Baoyu Zhao

Keyword(s):

Energy Metabolism ◽

Growth Factor ◽

Lipid Oxidation ◽

Dairy Cows ◽

Fibroblast Growth Factor ◽

Signaling Pathway ◽

Whole Body ◽

Optimal Time ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth

Abstract Background: Fibroblast growth factor 21 (FGF21) plays essential roles in the regulation of whole body energy metabolism. However, it is not entirely clear for dairy cows whether FGF21 activates AMPK signaling pathway and what will be affected for lipid metabolism in bovine hepatocytes. Methods: Bovine hepatocytes were isolated from caudate lobes by using three-step of perfusion and collagenase digestion method. The accumulation of TG and the secretion of VLDL were examined in hepatocytes and supernatant, respectively. The expressions of the metabolic key factors were detected by Real-time PCR and Western Blot.Results: The 4th hour is the optimal time that FGF21 activates AMPK. FGF21 has significant dose-dependent inhibition of TG in bovine hepatocytes; and high concentration (1800 pg/mL) significantly promoted VLDL secretion at 4 h. The protein expression of APOB 100, APOE and MTTP, which are components of VLDL, were stimulated by FGF21, and all the mRNA expression reached the peak point (P < 0.01) at medium concentration (900 pg/mL). Interestingly, the proteins associated with lipid transportation were promoted too, such as LDLR, CD36, L-FABP. To some extent, meanwhile, it could be observed that some genes regulating lipid oxidation were strengthened following FGF21 treatment. In detail, ACOX1 and SIRT1 were very sensitive to the concentration of FGF21, showing remarkable difference at low concentration (P < 0.01); PGC-α, PPAR-α and CPT-1 showed significant changes at 900 pg/mL (P < 0.01); CPT-2 required a higher concentration to achieve significant enhancement. However, the results had a negative impact on lipogenesis. SREBP1c, ACC, FASN and ACLY were inhibited after treatment with low or medium doses of FGF21 (P < 0.01). Conclusion: FGF21 can promote lipid oxidation and transport, while inhibit lipid synthesis via activating AMPK signalling pathway in primary hepatocytes of dairy cows, thereby participation in the adaptive regulation of energy metabolism.

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