The effects of leptin on plasma concentrations of prolactin, growth hormone, and melatonin vary depending on the stage of pregnancy in sheep1

Szczęsna, M.; Kirsz, Katarzyna; Misztal, Tomasz; Molik, Edyta; Zieba, D

doi:10.1093/jas/sky203

Cited by 3 publications

(4 citation statements)

References 47 publications

(57 reference statements)

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“…Our results here demonstrate that leptin inhibits melatonin synthesis in pigs, which is in agreement with the reports in rats and ewes, 10,[35][36][37] but there are few reports about the leptin signaling pathways and the related mechanisms in the pineal gland. The results of the present study detailed the signaling pathway of leptin inhibiting melatonin synthesis in porcine pineal glands and proved that miR-7 is a mediatory molecule of inhibition of melatonin synthesis by leptin in porcine pineal glands.…”

Section: Discussionsupporting

confidence: 93%

“…It is known that leptin is an important hormone which inhibits melatonin synthesis in the pineal gland, but the mechanisms by which leptin inhibits melatonin synthesis and the interaction between leptin and miR‐7 remained to be clarified. We thus assayed the effects of leptin on miR‐7 and Aanat expression in the cultured porcine pinealocytes and melatonin levels in the culture media.…”

Section: Resultsmentioning

confidence: 99%

“…Leptin is a 16‐kDa peptide hormone that is mainly produced by adipocytes. It has been demonstrated that leptin exerts dual effects on melatonin synthesis in different seasons and at different physiological stages in ewe pineal glands, although it is a master regulator of energy balance and has the function of modulating glucose homeostasis, neuroendocrine axes, autonomic nervous system, and neural plasticity . Leptin signals are transduced by binding to their corresponding membrane receptor, thus activating the intracellular JAK/STAT3, PI3K/AKT, and MAPK signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA‐7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland

Qiu

Zhang

Zhou

et al. 2019

Journal of Pineal Research

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MicroRNAs, including microRNA‐7 (miR‐7), are important modulators of numerous gene expressions and the related biological processes. Melatonin is a key hormone regulating daily and seasonal rhythms, in which a variety of positive and negative regulatory factors, such as norepinephrine (NE) and leptin, are involved. However, the interactions among these factors and the mechanisms remain to be elucidated. The aims of the present study were to identify the functions and the related mechanisms of miR‐7 in regulating melatonin synthesis and secretion through in vitro and in vivo experiments in pineal gland of pigs, which is an important animal model for agricultural and biomedical studies. Our results firstly show that miR‐7 is specifically expressed in porcine pinealocytes and negatively regulates melatonin synthesis. The further functional studies show that the dynamic expression levels of miR‐7 are contrary to the melatonin levels throughout the day, and the forced inhibition of endogenous miR‐7 in porcine pinealocytes sharply increases arylalkylamine N‐acetyltransferase (AANAT) expression by 80.0% (P = 0.0031) and melatonin levels by 81.0% (P = 0.0421), whereas miR‐7 over‐expression down‐regulates AANAT expression by 38.6% (P = 0.0004) and melatonin levels by 37.6% (P = 0.0212). In addition, the miR‐7 expression is up‐regulated by leptin through the JAK/STAT3 signaling pathway, and the in vivo intracerebroventricular injection of leptin increases miR‐7 expression by 80.0% (P = 0.0044) in porcine pineal glands and reduces melatonin levels by 57.1% (P = 0.0060) compared with the controls. This functional inhibition of melatonin synthesis by miR‐7 is accomplished by its binding to the 3′‐UTR of Raf1. Further, our results demonstrate that the RAF1/MEK/ERK signaling pathway mediates NE‐induced AANAT expression, whereas leptin attenuates NE's function through miR‐7. Taken together, the results demonstrated that leptin activates the JAK/STAT3 signaling pathway to increase the expression of miR‐7, which acts as a negative regulatory molecule inhibiting NE‐activated RAF1/MEK/ERK signaling pathway by targeting Raf1, resulting in decreased AANAT expression and melatonin synthesis. These findings suggest that miR‐7 is a novel negative regulator of melatonin synthesis and links leptin‐ and NE‐mediated signaling pathways in porcine pineal glands, which will contribute to our understanding in the establishment of the biological rhythms resulting from melatonin.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MicroRNA‐7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland

Qiu

Zhang

Zhou

et al. 2019

Journal of Pineal Research

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“…When different sources of Ca salts of FA (0.39% of the diet) were fed to pregnant ewes, the supplementation with EPA and DHA increased leptin mRNA relative abundance in the SC adipose tissue (Coleman et al, 2018c). The differences observed in results comparing previous studies (Reseland et al, 2001;Coleman et al, 2018c) and the quadratic response observed in this experiment may be due to the interaction of the amounts and types of FA in each experiment (Yang et al, 2016), and the interaction with stage of gestation (Szczesna et al, 2018). The mechanism of how different FA at different concentrations regulate leptin mRNA relative abundance remains unclear.…”

Section: Ewe Performance and Sc Adipose Tissue Mrna Relative Abundancementioning

confidence: 49%

Supplementation with eicosapentaenoic and docosahexaenoic acids in late gestation in ewes changes adipose tissue gene expression in the ewe and growth and plasma concentration of ghrelin in the offspring1

Nickles

Hamer

Coleman

et al. 2019

Journal of Animal Science

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Omega-3 long chain fatty acids have a positive impact on production. When consumed during late gestation, it might have fetal programming effects on the fetus, which will have lifelong impacts on development and production. The objectives of the present study were to evaluate the effect of increasing doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet of ewes in the last third of gestation on their body weight (BW), subcutaneous adipose tissue relative mRNA abundance of genes associated with adipose tissue metabolism, and growth performance and plasma metabolites and hormones of their offspring during the finishing phase. Ewes (n = 72) were blocked by BW and allotted to pens (8 per treatment) with 3 ewes per pen. Ewes were supplemented with an EPA and DHA source (Strata G113) at concentrations of 0, 1, or 2% of dry matter intake during the last 50 d of gestation. At lambing, all ewes were penned together and offered the same diet. After weaning at 60 d of age, lambs were blocked by BW and sex and fed for 56 d. All lambs were fed the same pellet diet (61.09% ground corn, 24.08% soy hulls, 11.09% soybean meal, 1.48% Ca salt of palm oil, and 2.26% mixed mineral vitamin), and were weighed every 14 d until the end of the trial. Blood samples were collected on the weight sampling days. Dry matter intake and refusals were weighed daily. Data were analyzed as a randomized complete block design with repeated measurements (SAS 9.4). Polynomial contrast (linear-L and quadratic-Q) was used for mean separation. There were no differences in ewe body condition score, milk production, milk fat, or milk protein, but there was a trend for increased (L, P = 0.06) lactose concentration, and also differences in DGAT1 (L, P = 0.04), Δ5-desaturase (Q, P = 0.06) and Δ6-desaturase (Q, P = 0.07), PPARα (Q, P = 0.03), ELOVL2 and 5 (Q, P < 0.07), FABP4 (Q, P = 0.04), FATP1 (Q, P = 0.06), leptin (Q, P = 0.02), and resistin (L, P = 0.05). Feeding pregnant ewes an increased amount of EPA and DHA in late gestation increased final BW (L, P = 0.01), ADG (L, P = 0.04; Q, P = 0.01), DMI (Q, P ≤ 0.01), plasma glucose concentration (L, P = 0.04), and trended to decrease ghrelin concentrations (L, P = 0.07) in offspring during the finishing period. Dam supplementation did not affect G:F, nor plasma NEFA concentration (P ≥ 0.53) of lambs. Therefore, increasing supplementation of EPA and DHA in pregnant ewes has an impact on offspring performance, increasing DMI, ADG, and BW.

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Transcript Abundances of the Prolactin Receptor, the Leptin Receptor and their Major Suppressor in the Sheep Mammary Gland During Pregnancy and Lactation

Szczęsna

Kirsz

Nowakowski

et al. 2020

Annals of Animal Science

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AbstractThis study aimed to expand the knowledge of the interactions between prolactin (PRL) and leptin in the ovine mammary gland during pregnancy and lactation; we examined the mRNA expression of prolactin receptor (PRLR), the long form of the leptin receptor (LRb) and suppressor of cytokine signaling (SOCS)-3 in mammary gland biopsies collected on days 60, 90 and 120 of pregnancy and on days 30, 60 and 90 of lactation (n = 6 for each time point), along with the plasma PRL and leptin concentrations. The PRL concentrations were stable throughout pregnancy and increased during lactation. The plasma leptin concentrations were comparable among nonpregnant, early-pregnant, late-pregnant and lactating ewes, but this metric peaked during mid-pregnancy. Expression of PRLR and SOCS-3 in the mammary gland fluctuated during the transition from pregnancy to lactation, and differences in LRb expression occurred during the late stages of lactation. The LRb transcript abundance was approximately 31 times higher in ewes on day 60 of lactation than in early-lactating ewes. Expression of SOCS-3 mRNA in biopsies gradually decreased over the course of pregnancy and reached a minimum value during late pregnancy. After lambing, the transcript level of SOCS-3 increased and peaked on day 60 of lactation. During pregnancy, the plasma PRL concentration positively correlated with the abundances of PRLR (r = 0.971, P < 0.01) and SOCS-3 (r = 0.818, P < 0.05). Positive correlations were also observed between the transcript abundances of SOCS-3 and LRb (r = 0.854, P < 0.05). The variations observed in the plasma PRL and leptin concentrations and the changes in expression of key leptin and PRL signal transduction pathway components, such as PRLR, LRb and SOCS-3, indicate that the efficacies of both hormone actions are modulated in a multilevel manner throughout pregnancy and lactation. These interactions may regulate the ability of the mammary gland to respond to current energy requirements and challenges, thus affecting milk yield and lactation duration.

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The effects of leptin on plasma concentrations of prolactin, growth hormone, and melatonin vary depending on the stage of pregnancy in sheep1

Cited by 3 publications

References 47 publications

MicroRNA‐7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland

MicroRNA‐7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland

Supplementation with eicosapentaenoic and docosahexaenoic acids in late gestation in ewes changes adipose tissue gene expression in the ewe and growth and plasma concentration of ghrelin in the offspring1

Transcript Abundances of the Prolactin Receptor, the Leptin Receptor and their Major Suppressor in the Sheep Mammary Gland During Pregnancy and Lactation

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