Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice

Stokar, Joshua; Gurt, Irina; Cohen-Kfir, Einav; Yakubovsky, O; Hallak, Noa; Benyamini, Hadar; Lishinsky, Natan; Offir, Neta; Tam, Josef; Dresner–Pollak, Rivka

doi:10.1016/j.molmet.2022.101482

Cited by 10 publications

(13 citation statements)

References 94 publications

(110 reference statements)

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“…Additionally, hepatic cells treated with cholesterol exhibited decreased Enho mRNA expression (29). Given the initial induction of Enho mRNA expression by fat-enriched diets, Kumar et al (5) Recently, hepatic Enho mRNA expression has been reported to be decreased with the loss of ovarian hormones via ovariectomy (136).…”

Section: Hepatic Enho Regulationmentioning

confidence: 99%

Section: Hepatic Enho Regulationmentioning

confidence: 99%

“…Subsequently, estrogen-treated liver cells from mice and humans exhibited an increase in Enho mRNA expression (136). There is conflicting evidence on whether Enho has an estrogen response element near its promoter of Enho (136,137). Given that Stokar et al (136) intended on assessing biomarkers to alleviate metabolic derangement in postmenopausal women, the influence of estrogen signaling on hepatic Enho mRNA expression may be indicative of differential regulation of Enho between the sexes.…”

Section: Hepatic Enho Regulationmentioning

confidence: 99%

“…There is conflicting evidence on whether Enho has an estrogen response element near its promoter of Enho (136,137). Given that Stokar et al (136) intended on assessing biomarkers to alleviate metabolic derangement in postmenopausal women, the influence of estrogen signaling on hepatic Enho mRNA expression may be indicative of differential regulation of Enho between the sexes. Interestingly, hepatocytes derived from male, but not female, mice exhibited elevated Enho mRNA expression (137).…”

Section: Hepatic Enho Regulationmentioning

confidence: 99%

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Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

Jurrissen

Ramirez‐Perez

Cabral-Amador

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

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Adropin is a peptide largely secreted by the liver and known to regulate energy homeostasis; however, it also exerts cardiovascular effects. Herein, we tested the hypothesis that low circulating levels of adropin in obesity and type 2 diabetes (T2D) contribute to arterial stiffening. In support of this hypothesis, we report that obesity and T2D is associated with reduced levels of adropin (in liver and plasma) and increased arterial stiffness in mice and humans. Establishing causation, we show that mesenteric arteries from adropin knockout mice are also stiffer, relative to arteries from wild-type counterparts, thus recapitulating the stiffening phenotype observed in T2D db/db mice. Given the above, we performed a set of follow-up experiments, in which we found that: 1) exposure of endothelial cells or isolated mesenteric arteries from db/db mice to adropin reduces filamentous actin (F-actin) stress fibers and stiffness; 2) adropin-induced reduction of F-actin and stiffness in endothelial cells and db/db mesenteric arteries is abrogated by inhibition of nitric oxide (NO) synthase; and 3) stimulation of smooth muscle cells or db/db mesenteric arteries with a NO mimetic reduces stiffness. Last, we demonstrated that in vivo treatment of db/db mice with adropin for four weeks reduces stiffness in mesenteric arteries. Collectively, these findings indicate that adropin can regulate arterial stiffness, likely via endothelial-derived NO, and thus support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.

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Section: Hepatic Enho Regulationmentioning

confidence: 99%

Section: Hepatic Enho Regulationmentioning

confidence: 99%

Section: Hepatic Enho Regulationmentioning

confidence: 99%

Section: Hepatic Enho Regulationmentioning

confidence: 99%

See 2 more Smart Citations

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

Jurrissen

Ramirez‐Perez

Cabral-Amador

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

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“…It is well known that estrogen levels decline rapidly in the menopause stage. It has been recently reported that hepatic adropin gene expression is regulated by estrogen, and its downregulation is associated with adverse metabolic phenotypes in ovariectomized mice [ 13 , 14 ]. Adropin can be linked with inflammation, so a decrease in adropin levels may be associated with an increase in inflammation [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Elastic band resistance training increases adropin and ameliorates some cardiometabolic risk factors in elderly women: A quasi-experimental study

Jazi

Sarteshnizi

Fathi

et al. 2022

BMC Sports Sci Med Rehabil

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Background The decline in adropin over the aging process is associated with cardiometabolic risks, and resistance training may affect this decline. We hypothesized that elastic band resistance training (EBRT) would be an effective exercise for increasing adropin and improving the cardiometabolic profile in elderly women. Methods We randomly assigned 28 overweight elderly women (age = 74.04 ± 4.69 years) into one of two groups, EBRT (n = 14) or control (CON; n = 14), to participate in a 12-week (3d/wk) supervised EBRT program. The serum levels of adropin and cardiometabolic risk factors were evaluated at baseline and after the intervention. The exercise training protocol consisted of three supervised training sessions (55 min) per week for 12 weeks. Data were analyzed using two-way repeated-measures ANOVA and Pearson correlation coefficient. Results EBRT significantly increased serum adropin levels (p = 0.026), number of repetitions in the 30-second chair-stand test (p = 0.016), and number of repetitions in the 30-second arm curl test (p = 0.032). Moreover, EBRT significantly decreased serum levels of insulin (p = 0.035), TNF-α (p = 0.046), hsCRP (p = 0.037), and insulin resistance (p = 0.045) as well as body fat percentage (p = 0.023). There were no significant between-group differences (p > 0.05) in glucose, TC, TG, LDL-C, HDL-C, BMI, and WHR; however, glucose, TC, TG, and BMI significantly changed in the EBRT group (within-group). Furthermore, adropin correlated with body fat percentage (p = 0.020) and BMI (p = 0.014) at pretest and with body fat percentage at posttest (p = 0.016), however, delta values were not significantly related. No correlation was observed between adropin and other biomarkers at any stage of the study. Conclusion EBRT can increase serum adropin levels, which has been associated with improved insulin sensitivity, inflammation, body fat percentage, and physical function in overweight elderly women.

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Adropin may promote insulin stimulated steroidogenesis and spermatogenesis in adult mice testes

Tripathi,

Maurya,

Singh

2023

J Exp Zool Pt A

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Adropin is a versatile peptide which was discovered as a novel metabolic hormone that is involved in the regulation of lipid and glucose homeostasis. However, its possible role in the testicular function is not yet understood. The aim of our study was to explore the distribution pattern of adropin and GPR19 in various cell types and its possible role in testicular functions of adult mice. Immunohistochemical study revealed the intense immunoreactivity of adropin in the Leydig cells, while GPR19 showed intense immunoreactivity in the pachytene spermatocytes and mild immunoreactivity in Leydig cells and primary as well as secondary spermatocytes in mouse testis. Enho mRNA was also found to be expressed in the mouse testis. These findings suggested that adropin‐GPR19 signaling may act in autocrine/paracrine manner to modulate testicular functions. Furthermore, to find out the direct role of adropin in the testicular function, in vitro study was performed in which testicular slices were cultured with adropin alone (10 and 100 ng/mL) and in combination with insulin (5 μg/mL). Adropin alone inhibited testicular testosterone synthesis by inhibiting the expression of P450‐SCC, 3β‐HSD, and 17β‐HSD while along with insulin stimulated the testicular testosterone synthesis by increasing the expression of GPR19, IR, StAR, P450‐SCC, 3β‐HSD, and 17β‐HSD. Adropin alone or in combination with insulin promoted germ cell survival and proliferation by upregulating the expression of PCNA, Bcl2, and pERK1/2. Thus, it can be concluded that adropin‐GPR19 signaling promotes insulin stimulated steroidogenesis and germ cell survival as well as proliferation in the mice testes in an autocrine/paracrine manner.

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Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice

Cited by 10 publications

References 94 publications

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

Elastic band resistance training increases adropin and ameliorates some cardiometabolic risk factors in elderly women: A quasi-experimental study

Adropin may promote insulin stimulated steroidogenesis and spermatogenesis in adult mice testes

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