Downregulation of Kcnq1ot1 attenuates β-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis

Li, Yanli; Chen, Yalan; Liu, Ziyu; Lin, BinLiang; Deng, Xiaoyi; Xiao, Qiwen; Chen, Zhishan; Ye, Huiyu; Chen, Danrui; Su, Yanna; Li, Wangen; Xu, Wen

doi:10.1007/s00592-022-01871-6

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…Linear correlation analysis indicated that most of these genes were closely correlated with Lep mRNA expression, implying that they may be involved in the inhibitory effects of paternal n-3 PUFA supplementation on leptin production. This is consistent with other reports that imprinted genes may regulate leptin expression (47)(48)(49)(50)(51)(61)(62)(63)(64)(65)(66)(67)(68). Simultaneously, the testes in juvenile F1 offspring, and adult F1 and F2 offspring had altered expression of the same genes, Plagl1, Cdkn1c, Kcnq1ot1, Peg3, and Grb10, upon paternal n-3 PUFA supplementation.…”

Section: Frontiers Insupporting

confidence: 92%

“…Similarly, Magel2-null pups endure growth retardation after birth, equalize their mean weight to wild-type levels at a young age, and subsequently gain more weight than their wild-type littermates in adulthood, with a higher plasma leptin level (59), due to decline in leptin sensitivity (60). Although their contribution to leptin expression has not been reported, Plagl1, Cdkn1c, and Kcnq1ot1 have been found to be involved in adiposity and obesity (61)(62)(63)(64)(65)(66)(67)(68), implying that they may impact leptin expression in the adipose tissue. Beyond its association with metabolic, genetic, and neoplastic illnesses through multiple pathways (61), Plagl1 has been found to be highly expressed in the white adipose tissue of adult rats, as compared to the other organs and tissues, and has a positive correlation with PPARγ and fatty acid binding protein 4 (62).…”

Section: Introductionmentioning

confidence: 99%

“…Using a transgenic mouse model, Vega-Benedetti et al found that overexpression of Cdkn1c during development protects against age-and dietinduced obesity, by promoting brown adipose tissue formation, with reduced adiposity (65,66). The expression of Kcnq1ot1 is downregulated in the mouse cartilage tissue of osteoarthritis and islets in high-fat-induced obesity, and knockdown of Kcnq1ot1 in vivo reduces glucose tolerance and insulin secretion (67,68).…”

Section: Introductionmentioning

confidence: 99%

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Paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids programs offspring leptin expression and gene imprinting in mice

et al. 2022

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BackgroundThis study determined the effects of the paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids (PUFAs) on leptin expression in the offspring and associated gene imprinting in a mouse model.MethodsThree- to four-week-old male C57BL/6J mice (F0) were fed an n-3 PUFA-deficient (n-3 D) diet, a diet with normal n-3 PUFA content (n-3 N; n-6: n-3 = 4.3:1), or a diet with a high n-3 PUFA content (n-3 H; n-6: n-3 = 1.5:1) for 8 weeks. Two subsequent generations were generated by mating F0 and F1 male mice with 10-week-old virgin female C57 BL/6J mice, to produce F1 and F2 offspring.ResultsCompared to the paternal n-3 D diet, paternal n-3 N and n-3 H diets reduced adipose mRNA expression of leptin (Lep) and its plasma concentrations in juvenile F1 male and female offspring, and adult F1 male and F2 female offspring, with upregulated Lep receptor mRNA expression in the hypothalamus. Meanwhile, paternal n-3 N and n-3 H diets altered the expression of the imprinted genes H19, Igf2, Igf2r, Plagl1, Cdkn1c, Kcnq1ot1, Peg3, and Grb10 in the adipose tissue of juvenile and adult F1 males, with almost no effects on F1 females, while more effects were observed in the adult F2 females than F2 males. Principal component analysis verified that Plagl1, Cdkn1c, and Kcnq1ot1 contributed the most to variation in adipose tissue expression in all offspring. Some of these genes (Plagl1, Cdkn1c, Kcnq1ot1, Peg3, and Grb10) were altered by the paternal n-3 N and n-3 H diets in the F1 and F2 generation testes as well. Furthermore, adipose Lep expression was positively correlated with expressions of H19, Igf2r, Plagl1, and Kcnq1ot1 in juvenile F1 males and females, negatively correlated with the Kcnq1ot1 expression in adult F1 males, and positively correlated with the Plagl1 expression in adult F2 females.ConclusionThese data imply that paternal Plagl1, Cdkn1c, and Kcnq1ot1 might be part of the pathways involved in offspring leptin programming. Therefore, a lower ratio of n-6: n-3 PUFAs, with higher intake of n-3 PUFAs in paternal pre-conception, may help maintain the offspring’s optimal leptin pattern in a sex-specific manner through multiple generations, and thereby, be beneficial for the offspring’s long-term health.

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Section: Frontiers Insupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids programs offspring leptin expression and gene imprinting in mice

et al. 2022

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“…Among the altered lncRNAs, Kcnq1ot1 was significantly increased at 24-h after ethanol treatment but decreased at 72-h after ethanol treatment. In previous studies, down-regulation of Kcnq1ot1 inhibited β-cell proliferation, resulting in impaired insulin synthesis [56], and its overexpression ameliorated osteogenic differentiation in human bone mesenchymal stem cells infected by bacteria [57]. Considering previous research, Kcnq1ot1 plays a role in helping cells proliferate and differentiate.…”

Section: Discussionmentioning

confidence: 87%

Effects of Ethanol on Expression of Coding and Noncoding RNAs in Murine Neuroblastoma Neuro2a Cells

Choi

Cho

Kim

et al. 2022

IJMS

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Excessive use of alcohol can induce neurobiological and neuropathological alterations in the brain, including the hippocampus and forebrain, through changes in neurotransmitter systems, hormonal systems, and neuroimmune processes. We aimed to investigate the effects of ethanol on the expression of coding and noncoding RNAs in a brain-derived cell line exposed to ethanol. After exposing Neuro2a cells, a neuroblastoma cell line, to ethanol for 24 and 72 h, we observed cell proliferation and analyzed up- and downregulated mRNAs and long noncoding RNAs (lncRNAs) using total RNA-Seq technology. We validated the differential expression of some mRNAs and lncRNAs by RT-qPCR and analyzed the expression of Cebpd and Rnu3a through knock-down of Cebpd. Cell proliferation was significantly reduced in cells exposed to 100 mM ethanol for 72 h, with 1773 transcripts up- or downregulated by greater than three-fold in ethanol-treated cells compared to controls. Of these, 514 were identified as lncRNAs. Differentially expressed mRNAs and lncRNAs were mainly observed in cells exposed to ethanol for 72 h, in which Atm and Cnr1 decreased, but Trib3, Cebpd, and Spdef increased. On the other hand, lncRNAs Kcnq1ot1, Tug1, and Xist were changed by ethanol, and Rnu3a in particular was greatly increased by chronic ethanol treatment through inhibition of Cebpd. Our results increase the understanding of cellular and molecular mechanisms related to coding and noncoding RNAs in an in vitro model of acute and chronic exposure to ethanol.

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“…miR-15b is known to induce the apoptosis of rat activated pancreatic stellate cells in vitro . Recently, there was a report that miR-15b-5p can target cyclin D1 and cyclin D2 to attenuate pancreatic β-cell proliferation and insulin secretion ( 112 ). Su et al ( 113 ) found that miR-15b was increased in the islets of LP offspring at 8 weeks of age, impairing glucose metabolism by targeting cyclin D1 and cyclin D2 ( Table 1 ).…”

Section: Role Of Mirnas In Glucose Metabolism In Offspringmentioning

confidence: 99%

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism

Zeng

Zhang

et al. 2022

Front. Nutr.

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Early life nutrition is associated with the development and metabolism in later life, which is known as the Developmental Origin of Health and Diseases (DOHaD). Epigenetics have been proposed as an important explanation for this link between early life malnutrition and long-term diseases. Non-coding RNAs (ncRNAs) may play a role in this epigenetic programming. The expression of ncRNAs (such as long non-coding RNA H19, microRNA-122, and circular RNA-SETD2) was significantly altered in specific tissues of offspring exposed to maternal malnutrition. Changes in these downstream targets of ncRNAs lead to abnormal development and metabolism. This review aims to summarize the existing knowledge on ncRNAs linking the maternal nutrition condition and offspring metabolic diseases, such as obesity, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD).

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Downregulation of Kcnq1ot1 attenuates β-cell proliferation and insulin secretion via the miR-15b-5p/Ccnd1 and Ccnd2 axis

Cited by 10 publications

References 40 publications

Paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids programs offspring leptin expression and gene imprinting in mice

Paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids programs offspring leptin expression and gene imprinting in mice

Effects of Ethanol on Expression of Coding and Noncoding RNAs in Murine Neuroblastoma Neuro2a Cells

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism

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