Metformin and AMP Kinase Activation Increase Expression of the Sterol Transporters ABCG5/8 (ATP-Binding Cassette Transporter G5/G8) With Potential Antiatherogenic Consequences

Molusky, Matthew M.; Hsieh, Joanne; Lee, Samuel X.; Ramakrishnan, Rajasekhar; Tascau, Liana; Haeusler, Rebecca A.; Accili, Domenico; Tall, Alan R.

doi:10.1161/atvbaha.118.311212

Cited by 33 publications

(21 citation statements)

References 79 publications

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“…Molusky MM et al [ 98 ] reported that metformin might upregulate macrophage RCT. The final steps of RCT are mediated by the sterol transporters, ABCG5 and ABCG8, which facilitate hepatobiliary transport of cholesterol.…”

Section: Drug That Mediate Abc Transporters: Abc Transporter Antagonimentioning

confidence: 99%

The impact of ATP-binding cassette transporters on metabolic diseases

Lü

2020

Nutr Metab (Lond)

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Currently, many people worldwide suffer from metabolic diseases caused by heredity and external factors, such as diet. One of the symptoms of metabolic diseases is abnormal lipid metabolism. ATP binding cassette (ABC) transporters are one of the largest transport protein superfamilies that exist in nearly all living organisms and are mainly located on lipid-processing cells. ABC transporters have been confirmed to be closely related to the pathogenesis of diseases such as metabolic diseases, cancer and Alzheimer’s disease based on their transport abilities. Notably, the capability to transport lipids makes ABC transporters critical in metabolic diseases. In addition, gene polymorphism in ABC transporters has been reported to be a risk factor for metabolic diseases, and it has been reported that relevant miRNAs have significant roles in regulating ABC transporters. In this review, we integrate recent studies to examine the roles of ABC transporters in metabolic diseases and aim to build a network with ABC transporters as the core, linking their transport abilities with metabolic and other diseases.

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Section: Drug That Mediate Abc Transporters: Abc Transporter Antagonimentioning

confidence: 99%

The impact of ATP-binding cassette transporters on metabolic diseases

Lü

2020

Nutr Metab (Lond)

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“…Next, since CRY1 interacts with and modulates the activity of several NHRs [39,40], we assessed whether hepatic JMJD5 ablation impacted the expression profile of genes regulated by NHR partners of CRY1 (Fig 6D). In JMJD5-null livers, we observed increased levels of genes regulated by liver X receptor α and β (LXRα/β) and liver receptor homolog 1 (LRH1) ( Abcg5 and Abcg8) [41–43], peroxisome proliferator–activated receptor δ (PPARδ) ( Lpl ) [44], and pregnane X receptor (PXR) ( Gstm3 ) [45,46]. On the other hand, in the absence of JMJD5, we saw decreases in expression of genes regulated by hepatocyte nuclear factor 4α (HNF4α) and PPARγ ( Cyp27a1) [47,48] and by glucocorticoid receptor (GR; Angptl4 , Pck1 , Lipg ) [39,49,50].…”

Section: Resultsmentioning

confidence: 99%

JMJD5 links CRY1 function and proteasomal degradation

Saran

Kalinowska

et al. 2018

PLoS Biol

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The circadian oscillator is a molecular feedback circuit whose orchestration involves posttranslational control of the activity and protein levels of its components. Although controlled proteolysis of circadian proteins is critical for oscillator function, our understanding of the underlying mechanisms remains incomplete. Here, we report that JmjC domain–containing protein 5 (JMJD5) interacts with CRYPTOCHROME 1 (CRY1) in an F-box/leucine-rich repeat protein 3 (FBXL3)-dependent manner and facilitates targeting of CRY1 to the proteasome. Genetic deletion of JMJD5 results in greater CRY1 stability, reduced CRY1 association with the proteasome, and disruption of circadian gene expression. We also report that in the absence of JMJD5, AMP-regulated protein kinase (AMPK)-induced CRY1 degradation is impaired, establishing JMJD5 as a key player in this mechanism. JMJD5 cooperates with CRY1 to repress circadian locomotor output cycles protein kaput (CLOCK)–brain and muscle ARNT-like protein 1 (BMAL1), thus linking CRY1 destabilization to repressive function. Finally, we find that ablation of JMJD5 impacts FBXL3- and CRY1-related functions beyond the oscillator.

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“…In vivo, treatment of mice fed a Western diet resulted in upregulation of these molecules with increased initial clearance of 3 H-cholesteryl ester HDL from plasma. However, fecal levels of 3 H-cholesterol were only marginally affected by metformin treatment 52 . In parallel, metformin treatment increased expression of the LDLR in the mice, thereby increasing uptake of nonradiolabeled cholesterol 52 .…”

Section: Liver Cells and Metabolic Perturbationmentioning

confidence: 86%

Metabolism, Obesity, and Diabetes Mellitus

Ruiz

López‐Díez

Arivazahagan

et al. 2019

ATVB

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Obesity and diabetes remain leading causes of reduced health span and life span throughout the world. Hence, it is not surprising that these areas are at the center of highly active areas of research. The identification of novel mechanisms underlying these metabolic disorders sets the stage for uncovering new potential therapeutic strategies. In this issue of Highlights in Arteriosclerosis, Thrombosis and Vascular Biology, we review recently published papers in the journal that add to our understanding of causes and consequences of obesity and diabetes and how these disorders impact metabolic function. Collectively, these studies in cultured cells to in vivo animal models to human subjects add to the growing body of evidence that both cell-intrinsic and cell-cell communication mechanisms collaborate in metabolic disorders to cause obesity, insulin resistance and diabetes and its complications. Adipocyte Biology: Effects on Vascular and Inflammatory HomeostasisAdipose tissue is a complex and highly active metabolic organ and adipose dysfunction is linked to cardiovascular disease 18 . Adipose tissues are diverse and specific depots have been characterized as "good fat" versus "bad fat." What accounts for these differences? Indeed, beyond adipocytes, multiple classes of immune cells, such as macrophages, T and B lymphocytes, T regulatory cells and NK cells; nerve tissue; stromovascular cells and endothelial cells (ECs), all housed within a biologically active connective tissue matrix, populate this tissue 19 . Recent studies have identified cell-intrinsic and cell-cell communication pathways linked to obesity and diabetes in adipose and other metabolic tissues, such as liver, skeletal muscle, and brain, and how their properties may affect vascular and inflammatory health and homeostasis. For example, cell-intrinsic roles for adipocytes in metabolic dysfunction were illustrated by studies in mice with adipocytespecific deletion of Nox4 (NADPH oxidase 4), using the Adipoq (Adiponectin) cre recombinase strategy for specific deletion of genes of interest in adipocytes. Mice were fed a high fat/high sucrose diet with added cholesterol. Mice devoid of adipocyte Nox4 exhibited

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Metformin and AMP Kinase Activation Increase Expression of the Sterol Transporters ABCG5/8 (ATP-Binding Cassette Transporter G5/G8) With Potential Antiatherogenic Consequences

Abstract: Supplemental Digital Content is available in the text.

Cited by 33 publications

References 79 publications

The impact of ATP-binding cassette transporters on metabolic diseases

The impact of ATP-binding cassette transporters on metabolic diseases

JMJD5 links CRY1 function and proteasomal degradation

Metabolism, Obesity, and Diabetes Mellitus

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