<i>Anxa2</i> gene silencing attenuates obesity-induced insulin resistance by suppressing the NF-κB signaling pathway

Wang, Yong; Cheng, Yunsheng; Yin, Xianzhen; Yu, Gang; Jia, Benli

doi:10.1152/ajpcell.00242.2018

Cited by 31 publications

(15 citation statements)

References 68 publications

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“…Decreased expression of adipogenic transcripts provided mechanistic insight for decreased fat hyperplasia with MusMyD88 −/− . For example, Anxa2 was shown to interact with the nuclear factor‐κB pathway as well as increase with obesity and contribute to insulin resistance . Caveolin‐related transcripts were shown to participate in lipid storage and increase in adipocytes with high‐fat diet , and high expression of Ehd1 has a genetic basis for susceptibility to obesity .…”

Section: Discussionmentioning

confidence: 99%

Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity‐Induced Adiposity and Insulin Resistance

Mahmassani

Reidy

McKenzie

et al. 2020

Obesity

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Objective Inactivity and inflammation are linked to obesity and insulin resistance. It was hypothesized that MyD88 (mediates inflammation) knockout from muscle (MusMyD88−/−) would prevent, whereas miR146a−/− (MyD88 inhibitor) would exacerbate, inactivity‐induced metabolic disturbances. Methods Cre‐control, MusMyD88−/−, and miR146a−/− mice were given running wheels for 5 weeks to model an active phenotype. Afterward, half were placed into a small mouse cage (SMC) to restrict movement for 8 days. Body composition, muscle (3H)2‐deoxyglucose uptake, visceral fat histology, and tissue weight (hind limb muscles, visceral fat, and liver) were assessed. In skeletal muscle and visceral fat, RNA sequencing and mitochondrial function were performed on female MusMyD88−/− and Cre‐control SMC mice. Results The SMC induced adiposity, hyperinsulinemia, and muscle insulin‐stimulated glucose uptake, which was worsened in miR146a−/− mice. In females, MusMyD88−/− mice were protected. Female MusMyD88−/− mice during the SMC period (vs. Cre‐control) exhibited higher Igf1 and decreased Ip6k3 and Trim63 muscle expression. Visceral fat transcript changes corresponded to improved lipid metabolism, decreased adipose expansion (Gulp1↑, Anxa2↓, Ehd1↓) and meta‐inflammation (Hmox1↓), and increased beiging (Fgf10↑). Ralgapa2, negative regulator of GLUT4 translocation, and inflammation‐related gene 993011J21Rik2 were decreased in both muscle and fat. Conclusions Whole‐body miR146a−/− exacerbated inactivity‐induced fat gain and muscle insulin resistance, whereas MusMyD88−/− prevented insulin resistance in female mice.

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Section: Discussionmentioning

confidence: 99%

Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity‐Induced Adiposity and Insulin Resistance

Mahmassani

Reidy

McKenzie

et al. 2020

Obesity

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“…This protein complex not only improved fatty acid uptake in these two often neighbouring cell types, but also enabled the transport of fatty acids from the endothelium to adipocytes. In further support of these observations, palmitate-inducible expression of inflammatory genes like IL-6, IL-1 beta and tumor necrosis factor alpha was markedly diminished upon AnxA2 suppression, while AnxA2 overexpression amplified the proinflammatory capacity of this saturated fatty acid [59].…”

Section: Annexin Expression Patterns In Adipose Tissue and Their Pmentioning

confidence: 93%

“…Overexpression of AnxA2 did not change any of these parameters. In addition, AnxA2 depletion was associated with less adipose tissue macrophages and inflammation, which was enhanced by AnxA2 overexpression [59]. Hence, several AnxA2 functions observed in cell-based studies might be relevant in stress-induced conditions in vivo, and, as outlined above, cell and animal studies support an involvement of AnxA2 in adipose tissue function.…”

Section: Annexin Expression Patterns In Adipose Tissue and Their Pmentioning

confidence: 99%

“…Firstly, several studies implicated AnxA2 in glucose homeostasis, in particular the insulin-inducible translocation of GLUT4, the main glucose transporter in adipocytes, from intracellular compartments to the cell surface. In one study, the silencing of AnxA2 in 3T3-L1 adipocytes improved insulin sensitivity and glucose uptake [59]. In striking contrast, others reported that AnxA2 inhibition or depletion, using antibodies or knockdown approaches, strongly reduced insulin-inducible GLUT4 translocation [51].…”

Section: Annexin Expression Patterns In Adipose Tissue and Their Pmentioning

confidence: 99%

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Annexins in Adipose Tissue: Novel Players in Obesity

Grewal

Enrich

Rentero

et al. 2019

IJMS

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Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to metabolic diseases related to obesity. In particular, the excess storage of lipids in adipose tissues disturbs cellular homeostasis. Amongst others, organelle function and cell signaling, often related to the altered composition of specialized membrane microdomains (lipid rafts), are affected. Within this context, the conserved family of annexins are well known to associate with membranes in a calcium (Ca2+)- and phospholipid-dependent manner in order to regulate membrane-related events, such as trafficking in endo- and exocytosis and membrane microdomain organization. These multiple activities of annexins are facilitated through their diverse interactions with a plethora of lipids and proteins, often in different cellular locations and with consequences for the activity of receptors, transporters, metabolic enzymes, and signaling complexes. While increasing evidence points at the function of annexins in lipid homeostasis and cell metabolism in various cells and organs, their role in adipose tissue, obesity and related metabolic diseases is still not well understood. Annexin A1 (AnxA1) is a potent pro-resolving mediator affecting the regulation of body weight and metabolic health. Relevant for glucose metabolism and fatty acid uptake in adipose tissue, several studies suggest AnxA2 to contribute to coordinate glucose transporter type 4 (GLUT4) translocation and to associate with the fatty acid transporter CD36. On the other hand, AnxA6 has been linked to the control of adipocyte lipolysis and adiponectin release. In addition, several other annexins are expressed in fat tissues, yet their roles in adipocytes are less well examined. The current review article summarizes studies on the expression of annexins in adipocytes and in obesity. Research efforts investigating the potential role of annexins in fat tissue relevant to health and metabolic disease are discussed.

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“…All data presented herein were obtained from refs. [44,54,55,70,72,74,75,78,88,95,96,98,102–111,116,119–121,124–130,132,134–137,140–144,147–156,158,159,161,163–171,173–176...…”

Section: Diet Composition and Exposure Timementioning

confidence: 99%

Modeling Diet‐Induced Metabolic Syndrome in Rodents

Leonardi

Gosmann

Zimmer

2020

Molecular Nutrition Food Res

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Standardized animal models represent one of the most valuable tools available to understand the mechanism underlying the metabolic syndrome (MetS) and to seek for new therapeutic strategies. However, there is considerable variability in the studies conducted with this essential purpose. This review presents an updated discussion of the most recent studies using diverse experimental conditions to induce MetS in rodents with unbalanced diets, discusses the key findings in metabolic outcomes, and critically evaluates what we have been learned from them and how to advance in the field. The study includes scientific reports sourced from the Web of Science and PubMed databases, published between January 2013 and June 2020, which used hypercaloric diets to induce metabolic disorders, and address the impact of the diet on metabolic parameters. The collected data are used as support to discuss variables such as sex, species, and age of the animals, the most favorable type of diet, and the ideal diet length to generate metabolic changes. The experimental characteristics propose herein improve the performance of a preclinical model that resembles the human MetS and will guide researchers to investigate new therapeutic alternatives with confidence and higher translational validity.

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Anxa2 gene silencing attenuates obesity-induced insulin resistance by suppressing the NF-κB signaling pathway

Cited by 31 publications

References 68 publications

Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity‐Induced Adiposity and Insulin Resistance

Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity‐Induced Adiposity and Insulin Resistance

Annexins in Adipose Tissue: Novel Players in Obesity

Modeling Diet‐Induced Metabolic Syndrome in Rodents

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