miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir

Bresciani, Elena; Saletti, Cecilia; Squillace, Nicola; Rizzi, Laura; Molteni, Laura; Meanti, Ramona; Omeljaniuk, Robert J.; Biagini, Giuseppe; Gori, Andrea; Locatelli, Vittorio; Torsello, Antonio

doi:10.3389/fphar.2019.00461

Cited by 15 publications

(18 citation statements)

References 55 publications

(75 reference statements)

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“…miR-218-2-3p expression was significantly increased at 2 h upon exposure to a lipid challenge in the duodenum and jejunum of male mice, and in the ileum of females. Recently, via loss and gain of function experiments, Bresciani et al showed that miRNA-218 targets the lipin-1 gene altering its functionality 30 . Members of the Lipin family have a critical role in the regulation of intestinal lipid homeostasis and chylomicron production 31 .…”

Section: Discussionmentioning

confidence: 99%

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Intestinal miRNAs regulated in response to dietary lipids

Gil-Zamorano

Tomé‐Carneiro

Hazas

et al. 2020

Sci Rep

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The role of miRNAs in intestinal lipid metabolism is poorly described. The small intestine is constantly exposed to high amounts of dietary lipids, and it is under conditions of stress that the functions of miRNAs become especially pronounced. Approaches consisting in either a chronic exposure to cholesterol and triglyceride rich diets (for several days or weeks) or an acute lipid challenge were employed in the search for intestinal miRNAs with a potential role in lipid metabolism regulation. According to our results, changes in miRNA expression in response to fat ingestion are dependent on factors such as time upon exposure, gender and small intestine section. Classic and recent intestinal in vitro models (i.e. differentiated Caco-2 cells and murine organoids) partially mirror miRNA modulation in response to lipid challenges in vivo. Moreover, intestinal miRNAs might play a role in triglyceride absorption and produce changes in lipid accumulation in intestinal tissues as seen in a generated intestinal Dicer1-deletion murine model. Overall, despite some variability between the different experimental cohorts and in vitro models, results show that some miRNAs analysed here are modulated in response to dietary lipids, hence likely to participate in the regulation of lipid metabolism, and call for further research.

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Section: Discussionmentioning

confidence: 99%

“…(a) Time-course(30,60, 120 and 240 min) expression of miRNAs showing significant differences in response to an oral lipid challenge in male C57BL/6 mice. Data are shown as mean ± SD; n ≥ 7.…”

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confidence: 99%

Intestinal miRNAs regulated in response to dietary lipids

Gil-Zamorano

Tomé‐Carneiro

Hazas

et al. 2020

Sci Rep

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“…Indeed, adipogenesis is a process in which there is marked change in the transcription profile. HIV-infection and HAART were reported to alter this profile [ 35 , 36 , 37 ]. Accordingly, many proteins, particularly several secreted factors, are newly synthesized during adipogenesis.…”

Section: Discussionmentioning

confidence: 99%

Cellular Mechanism Underlying Highly-Active or Antiretroviral Therapy-Induced Lipodystrophy: Atazanavir, a Protease Inhibitor, Compromises Adipogenic Conversion of Adipose-Derived Stem/Progenitor Cells through Accelerating ER Stress-Mediated Cell Death in Differentiating Adipocytes

Akita

Suzuki

Yoshimoto

et al. 2021

IJMS

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Lipodystrophy is a common complication in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART). Previous studies demonstrated that endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR) is involved in lipodystrophy; however, the detailed mechanism has not been fully described in human adipogenic cell lineage. We utilized adipose tissue-derived stem cells (ADSCs) obtained from human subcutaneous adipose tissue, and atazanavir (ATV), a protease inhibitor (PI), was administered to ADSCs and ADSCs undergoing adipogenic conversion. Marked repression of adipogenic differentiation was observed when ATV was administered during 10 days of ADSC culture in adipogenic differentiation medium. Although ATV had no effect on ADSCs, it significantly induced apoptosis in differentiating adipocytes. ATV treatment also caused the punctate appearance of CCAAT-enhancer-binding (C/EBP) protein homologous protein (CHOP), and altered expression of CHOP and GRP78/Bip, which are the representation of ER stress, only in differentiating adipocytes. Administration of UPR inhibitors restored adipogenic differentiation, indicating that ER stress-mediated UPR was induced in differentiating adipocytes in the presence of ATV. We also observed autophagy, which was potentiated in differentiating adipocytes by ATV treatment. Thus, adipogenic cell atrophy leads to ATV-induced lipodystrophy, which is mediated by ER stress-mediated UPR and accelerated autophagy, both of which would cause adipogenic apoptosis. As our study demonstrated for the first time that ADSCs are unsusceptible to ATV and its deleterious effects are limited to the differentiating adipocytes, responsible target(s) for ATV-induced lipodystrophy may be protease(s) processing adipogenesis-specific protein(s).

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“…17 HIV-infected patients with lipodystrophy or metabolic abnormalities due to ART have decreased lipin-1 mRNA expression in subcutaneous adipose tissues. 18 In differentiated 3T3-L1 cells, treatments with PIs resulted in reduction in lipin-1 mRNA expression by promoting the miRNA-218 expression. Although the role of miRNA is still ambiguous, it was reported to have a relationship with glucose transporter type 4 (GLUT-4) gene expression which is the insulin-stimulated glucose transporter.…”

Section: In Vitro Studiesmentioning

confidence: 96%

“…3T3-L1 adipocytes on exposure to lopinavir: ritonavir combination showed a significant reduction in lipid (−13.2% in concentration of 12 μM:3 μM and −14.5% in 16 μM:4 μM, P<0.05). 18 Caron et al 19 examined the long-term effects of NRTIs on lipid accumulation and mitochondrial function of differentiating 3T3-F442A and differentiated 3T3 adipocytes. Among the treated NRTIs, zidovudine (1 μM) and stavudine (10 μM) showed changes in lipid phenotype, content, and expression of metabolic markers.…”

Section: In Vitro Studiesmentioning

confidence: 99%

<p>Antiretroviral Therapy-Associated Metabolic Complications: Review of the Recent Studies</p>

Thet¹,

Siritientong²

2020

HIV

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The extensive utilization of antiretroviral therapy (ART) has successfully improved human immunodeficiency virus (HIV)-associated complications. The incidence of opportunistic infections is decreased by the viral load suppression and the CD4 count promotion. However, metabolic complications, commonly bone demineralization, lipodystrophy, and lactic acidosis, are arising following the adaptation of long-term ART. The events are not drug-specific, but the severity and incidence individually vary depending upon classes of drugs. Such concerning occurrences may lead to discontinuation of current therapy or switching to another regimen with fewer adverse effects. The purpose of this review is to demonstrate the common metabolic abnormalities associated with each class of widely used ART in people living with HIV (PLHIV). Electronic databases such as PubMed, ScienceDirect, Scopus, Google Scholar, SciFinder, and Web of Science were used for the literature search. A better understanding of ART-associated metabolic adverse effects is helpful in various clinical settings so that therapists may optimize treatments in this population.

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miRNA-218 Targets Lipin-1 and Glucose Transporter Type 4 Genes in 3T3-L1 Cells Treated With Lopinavir/Ritonavir

Cited by 15 publications

References 55 publications

Intestinal miRNAs regulated in response to dietary lipids

Intestinal miRNAs regulated in response to dietary lipids

Cellular Mechanism Underlying Highly-Active or Antiretroviral Therapy-Induced Lipodystrophy: Atazanavir, a Protease Inhibitor, Compromises Adipogenic Conversion of Adipose-Derived Stem/Progenitor Cells through Accelerating ER Stress-Mediated Cell Death in Differentiating Adipocytes

<p>Antiretroviral Therapy-Associated Metabolic Complications: Review of the Recent Studies</p>

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