scholarly journals Plasma FGF21 Is Elevated by the Intense Lipid Mobilization of Lactation

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4652-4661 ◽  
Author(s):  
Katie M. Schoenberg ◽  
Sarah L. Giesy ◽  
Kevin J. Harvatine ◽  
Matthew R. Waldron ◽  
Christine Cheng ◽  
...  

In many mammals, lactation success depends on substantial use of lipid reserves and requires integrated metabolic activities between white adipose tissue (WAT) and liver. Mechanisms responsible for this integration in lactation are poorly understood, but data collected in other conditions of elevated lipid use suggest a role for fibroblast growth factor-21 (FGF21). To address this possibility in the context of lactation, we studied high-yielding dairy cows during the transition from late pregnancy (LP) to early lactation (EL). Plasma FGF21 was nearly undetectable in LP, peaked on the day of parturition, and then stabilized at lower, chronically elevated concentrations during the energy deficit of EL. Plasma FGF21 was similarly increased in the absence of parturition when an energy-deficit state was induced by feed restricting late-lactating dairy cows, implicating energy insufficiency as a cause of chronically elevated FGF21 in EL. Gene expression studies showed that liver was a major source of plasma FGF21 in EL with little or no contribution by WAT, skeletal muscle, and mammary gland. Meaningful expression of the FGF21 coreceptor β-Klotho was restricted to liver and WAT in a survey of 15 tissues that included the mammary gland. Expression of β-Klotho and its subset of interacting FGF receptors was modestly affected by the transition from LP to EL in liver but not in WAT. Overall, these data suggest a model whereby liver-derived FGF21 regulates the use of lipid reserves during lactation via focal actions on liver and WAT.

2014 ◽  
Vol 307 (3) ◽  
pp. R290-R298 ◽  
Author(s):  
Yingjun Cui ◽  
Sarah L. Giesy ◽  
Mahmoud Hassan ◽  
Kristen Davis ◽  
Shuhong Zhao ◽  
...  

Female mammals call on hormonally driven metabolic adaptations to meet the energy demand of late pregnancy and lactation. These maternal adaptations preserve limiting nutrients and promote their transfer to the uterus during pregnancy or mammary gland during lactation. The novel metabolic hormone fibroblast growth factor-21 (FGF21) was recently shown to increase suddenly at the onset of lactation in dairy cows, but whether FGF21 is induced during the reproductive cycle of other mammals is unknown. To start addressing this question, we studied subsets of mice when virgin (V), on day 18 of pregnancy (P18) and on lactation day 1 (L1), L5 and L14. Plasma FGF21 increased from nearly undetectable levels to over 8 ng/ml between V and P18 and returned to V levels by L1. Gene expression studies showed that liver was the major source of plasma FGF21 at P18 with little or no contribution from other known expressing tissues or from the developing placenta and mammary epithelial cells. The increased FGF21 production at P18 was dissociated from plasma nonesterified fatty acids and liver lipids, unlike that seen in fasted V mice. Changes in FGF21 signaling components in target tissues were modest except for reduced β-Klotho and FGFR1c expression in P18 adipose tissue. The placenta expressed both β-Klotho and FGFR1c, raising the possibility that it responds to FGF21. In conclusion, maternal FGF21 is increased when products of conception account for ∼40% of maternal weight, suggesting that FGF21 orchestrates some of the adaptations needed to meet the energy demand of late pregnancy.


Author(s):  
Yue Wang ◽  
Xuemei Nan ◽  
Yiguang Zhao ◽  
Linshu Jiang ◽  
Hui Wang ◽  
...  

Milk microbiota and mediated metabolites directly affect the health of the udder in dairy cows. Inulin, a dietary prebiotic, can modulate the profile of gastrointestinal microbiota. However, whether the inulin intake affects the milk microbial population and metabolites remains unknown. In this study, forty subclinical mastitis (SCM) cows were randomly divided into 5 groups. Five inulin addition doses, 0, 100, 200, 300 and 400 g/d per cow, based on the same basal diet were supplemented, respectively. The experiments lasted for 8 weeks. The results showed lower relative abundance of mastitic-causing and pro-inflammation microbes in milk (i.e., Escherichia -Shigella , Pseudomonas , Rhodococcus and Burkholderia-Caballeronia-Paraburkholderia , etc.), and higher probiotics and commensal bacteria, such as, Lactobacillus , Bifidobacterium , etc. in the cows fed 300 g/d inulin, compared with the control group. Meanwhile, the levels of arachidonic acid pro-inflammatory mediators (leukotriene E3, 20-carboxy-leukotriene B4 and 12-Oxo-c-LTB3) and phospholipid metabolites were reduced, and the levels of compounds with antibacterial and anti-inflammatory potential (prostaglandin A1 and 8-iso-15-Keto-PGE 2 , etc.), and participating energy metabolism (citric acid and L-Carnitine, etc.) were elevated. These data suggested that inulin intake might modulate the microflora and metabolites level in extra-intestinal tissue, such as mammary gland, which provided an alternative for the regulation and mitigation for SCM. IMPORTANCE The profile of microbial community and metabolic activity in milk are main determinant of udder health status and milk quality. Recent studies have demonstrated that diet could directly modulate mammary gland microbiome. Inulin is a probiotic dietary fiber, which can improve the microbiota population in gastrointestinal tract. However, whether inulin intake can further regulate the profile of microbiota and metabolic activities in milk remains unclear. In subclinical mastitic cows, we found that inulin supplementation could reduce the abundance of Escherichia -Shigella , Pseudomonas , Rhodococcus , Burkholderia-Caballeronia-Paraburkholderia and the levels of (±)12, 13 - DiHOME, leukotriene E3 and 20-Carboxy-Leukotriene B4 etc., while, elevated the abundance of Lactobacillus , Bifidobacterium , and Muribaculaceae as well as the levels of prostaglandin A1 (PGA1), 8-iso-15-keto-PGE2 and benzoic acid etc., in milk. These data suggest that inulin intake affects the profile of microorganisms and metabolites in milk, which provides an alternative for the regulation of mastitis.


2003 ◽  
Vol 285 (5) ◽  
pp. R1107-R1115 ◽  
Author(s):  
Brian J. Leury ◽  
Lance H. Baumgard ◽  
Stephanie S. Block ◽  
Nthabisheng Segoale ◽  
Richard A. Ehrhardt ◽  
...  

After parturition, dairy cows suffer from an intense energy deficit caused by the onset of copious milk secretion and an inadequate increase in voluntary food intake. We previously showed that this energy deficit contributes to a decline in plasma leptin. This decline mirrors that of plasma insulin but is reciprocal to the profile of plasma growth hormone (GH), suggesting that both hormones may regulate plasma leptin in periparturient dairy cows. To study the role of insulin, hyperinsulinemic-euglycemic clamps were performed on six dairy cows in late pregnancy (LP, 31 days prepartum) and early lactation (EL, 7 days postpartum). Infusion of insulin (1 μg·kg body wt-1·h-1) caused a progressive rise in the plasma concentration of leptin that reached maximum levels at 24 h during both physiological states. At steady states, the absolute increase in plasma leptin was greater in LP than in EL cows (2.4 vs. 0.4 ng/ml). Insulin infusion increased leptin mRNA in adipose tissue during LP but not during EL. During lactation, mammary epithelial cells expressed leptin mRNA but insulin did not increase milk leptin output. In contrast, a 3-day period of GH administration had no effect on plasma leptin during LP or EL. Therefore, insulin increases plasma leptin in LP by stimulating adipose tissue synthesis but has only marginal effects in EL, when cows are in negative energy balance. Other factors, such as increased response of adipose tissue to β-adrenergic signals, probably contribute to the reduction of plasma leptin in early lactating dairy cows.


2017 ◽  
Vol 16 (1) ◽  
Author(s):  
I.S.B. Pinto ◽  
I. Fonseca ◽  
H.M. Brandão ◽  
J.C. Gern ◽  
A.S. Guimarães ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kim Hoa Ho ◽  
Annarita Patrizi

AbstractChoroid plexus (ChP), a vascularized secretory epithelium located in all brain ventricles, plays critical roles in development, homeostasis and brain repair. Reverse transcription quantitative real-time PCR (RT-qPCR) is a popular and useful technique for measuring gene expression changes and also widely used in ChP studies. However, the reliability of RT-qPCR data is strongly dependent on the choice of reference genes, which are supposed to be stable across all samples. In this study, we validated the expression of 12 well established housekeeping genes in ChP in 2 independent experimental paradigms by using popular stability testing algorithms: BestKeeper, DeltaCq, geNorm and NormFinder. Rer1 and Rpl13a were identified as the most stable genes throughout mouse ChP development, while Hprt1 and Rpl27 were the most stable genes across conditions in a mouse sensory deprivation experiment. In addition, Rpl13a, Rpl27 and Tbp were mutually among the top five most stable genes in both experiments. Normalisation of Ttr and Otx2 expression levels using different housekeeping gene combinations demonstrated the profound effect of reference gene choice on target gene expression. Our study emphasized the importance of validating and selecting stable housekeeping genes under specific experimental conditions.


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