Leptin decreases the expression of low-density lipoprotein receptor via PCSK9 pathway: linking dyslipidemia with obesity

Du, Ying; Li, Sha; Cui, Chuan-Jue; Zhang, Yan; Yang, Shengwen; Li, Jianjun

doi:10.1186/s12967-016-1032-4

Cited by 29 publications

(18 citation statements)

References 35 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As expected, the data showed that the inhibiting effect of liraglutide on PCSK9 was weakened after inhibition of HNF-1α by siRNA, suggesting that liraglutide reduced PCSK9 at least partly via HNF1α-dependent mechanism. Meanwhile, we found that SREBP-2 was not involved in the effect of liraglutide on PCSK9 (data not shown), which is supported by our previous studies [ 51 , 52 ]. Also, in the present study, liraglutide reduced PCSK9 expression in HepG2 and db/db mice but not in WT mice.…”

Section: Discussionsupporting

confidence: 87%

Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism

Yang

Cui

et al. 2018

Cardiovasc Diabetol

Self Cite

View full text Add to dashboard Cite

BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of cholesterol homeostasis, is associated with glucose metabolism. Liraglutide, a glucagon-like peptide-1 receptor agonist, can increase insulin secretion in a glucose-dependent manner and lower blood glucose. We aimed to investigate the relationship between liraglutide and PCSK9.MethodsAt the cellular level, the expressions of PCSK9 and hepatocyte nuclear factor 1 alpha (HNF1α) protein in HepG2 cells stimulated by liraglutide was examined using Western blot. Seven-week old db/db mice and wild type (WT) mice were administered either liraglutide (200 μg/kg) or equivoluminal saline subcutaneously, twice daily for 7 weeks. Fasting glucose level, food intake and body weight were measured every week. After the 7-week treatment, the blood was collected for lipid and PCSK9 levels detection and the liver was removed from the mice for oil red O staining, immunohistochemical analysis, immunofluorescence test and Western bolt.ResultsFirstly, liraglutide suppressed both PCSK9 and HNF1α expression in HepG2 cells in a time and concentration dependent manner. Secondly, liraglutide induced weight loss in WT and db/db mice, decreased serum PCSK9, glucose and lipid levels and improved hepatic accumulation in db/db but not WT mice. Thirdly, liraglutide reduced both hepatic PCSK9 and low-density lipoprotein receptor (LDLR) expression with a decrease in HNF1α in db/db mice but not in WT mice.ConclusionsLiraglutide suppressed PCSK9 expression through HNF1α-dependent mechanism in HepG2 cells and db/db mice, and decreased LDLR possibly via PCSK9-independent pathways in db/db mice.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0689-9) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 87%

Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism

Yang

Cui

et al. 2018

Cardiovasc Diabetol

Self Cite

View full text Add to dashboard Cite

show abstract

“…La leptine induit donc ainsi la dégradation du LDL-R. Elle s'oppose également à l'induction d'expression du LDL-R par les statines. Les études réalisées chez la souris montrent des résultats différents en fonction du sexe et de la présence ou non d'une lipodystrophie [3].…”

Section: Leptine Et Profil Lipidiqueunclassified

Effects of leptin and adiponectin on the cardiovascular system

Genoux¹,

Bastard²

2020

Annales De Biologie Clinique

View full text Add to dashboard Cite

Article reçu le 30 mars 2020, accepté le 31 mars 2020 Résumé. Une leptinémie élevée a été associée à une augmentation du risque cardiovasculaire. Cependant, des études épidémiologiques ne retrouvent pas cette association, suggérant des effets distincts de la leptine selon le contexte physiopathologique. Les études menées chez les souris déficientes en leptine ou en son récepteur sont également contradictoires. Elles montrent des effets protecteurs ou délétères selon le fond génétique de l'animal et des doses de leptine administrées, rendant l'interprétation des résultats délicate. Une adiponectinémie élevée est associée à un profil cardiovasculaire favorable. L'adiponectine a des effets athéroprotecteurs à tous les stades de développement de la plaque d'athérome. Cependant, ces mécanismes physiopathologiques ont été établis à partir de modèles cellulaires. De plus, les modèles murins utilisés ont un métabolisme des lipoprotéines différent de l'homme, ce qui complique l'extrapolation des résultats. Enfin, les études épidémiologiques montrent des résultats paradoxaux puisqu'une adiponectinémie élevée est associée à une augmentation de la mortalité cardiovasculaire et toutes causes confondues. Ceci illustre le paradoxe des adipokines et montrent la complexité de leur utilisation comme biomarqueurs dans les pathologies cardiovasculaires. Une résistance à l'action de ces adipokines pourrait expliquer ces discordances.

show abstract

“…For instance, adiponectin is involved in activities of cholesterol efflux, influencing overall reverse cholesterol transport and subsequent increasing plasma HDL-C levels [ 33 , 34 ]. Leptin particulates in cholesterol-regulating functions via proprotein convertase subtilisin/kexin type 9 pathway and down-regulates expression of LDL receptors in hepatocytes, leading to elevated plasma LDL-C levels and dyslipidemia [ 35 ]. High levels of HDL-C can lower your risk for cardiovascular diseases, while high LDL-C levels have opposite effects [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Relationships between depression and anxiety symptoms and adipocyte-derived proteins in postmenopausal women

Huang²,

Kor

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Introduction Studies on the association between adiponectin and leptin and anxiety and depression among postmenopausal women are limited. Therefore, the present study specifically evaluates the mutual relationships between adiponectin and leptin and anxiety and depression in postmenopausal women. Participants and design In this cross-sectional study, a total of 190 women aged 40–65 years were enrolled. Depression symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), and anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAM-A). Fasting specimens were collected to measure sex hormone, glucose, insulin, and adipokine levels. Multiple linear regression analysis was performed to evaluate the associations between depression and anxiety and adipocyte-derived hormones. Settings The study was performed in a hospital medical center. Results Among 190 enrolled postmenopausal women, Spearman’s rank correlation analysis revealed significant correlations between CES-D and HAM-A (r = 0.715, P < 0.0001), between CES-D and adiponectin (p = 0.009) and leptin (p = 0.015), and between HAM-A and adiponectin (p = 0.01) and leptin (p = 0.001). The subjects with CES-D ≥ 16 and with HAM-A ≥ 18 had higher adiponectin levels than those with CES-D < 16 and HAM-A < 18, respectively. After adjusting for age, body mass index, exercise, alanine amino transferase and parameters of lipid profiles, Log adiponectin levels were found to be significantly associated with both CES-D and HAM-A, and Log leptin levels were only significantly associated with HAM-A. Conclusions The data show that adiponectin and leptin levels are significantly associated with depression and anxiety symptoms. These results suggest that higher adiponectin and lower leptin levels may serve as potential markers related to anxiety and mood in postmenopausal women. More future research that is designed to deal with the important confounders (e.g., population heterogeneity) is needed to investigate comprehensively on these associations.

show abstract

Leptin decreases the expression of low-density lipoprotein receptor via PCSK9 pathway: linking dyslipidemia with obesity

Cited by 29 publications

References 35 publications

Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism

Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism

Effects of leptin and adiponectin on the cardiovascular system

Relationships between depression and anxiety symptoms and adipocyte-derived proteins in postmenopausal women

Contact Info

Product

Resources

About