During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization

Kim, Jong In; Park, Jeu; Ji, Yul; Jo, Kyuri; Han, Sun-Hee; Sohn, Jin Ho; Shin, Kyung Cheul; Han, Joo Seok; Jeon, Yong Geun; Nahmgoong, Hahn; Han, Kyung Hee; Kim, Jiwon; Kim, Sun; Choe, Sung Sik; Kim, Jae Bum

doi:10.1128/mcb.00210-19

Cited by 37 publications

(40 citation statements)

References 56 publications

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“…Our results are consistent with a recent study that demonstrated correlations between adipocyte size, actin cytoskeletal complexity, and insulin resistance [ 65 ]. These results differ from another study, however, in which it was reported that larger adipocytes with functional declines had reduced actin polymerization [ 66 ]. Interestingly, chemical compounds that interfere with actin cytoskeletal dynamics either by stabilizing actin polymerization or inhibiting polymerization have negative impacts on insulin-stimulated glucose uptake in adipocytes, apparently by disrupting glucose transporter type 4 (GLUT4) vesicular trafficking [ 67 , 68 ].…”

Section: Discussioncontrasting

confidence: 99%

Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFβ-SMAD signaling

Roh

Kumari

Taleb

et al. 2020

Molecular Metabolism

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Objective Obesity due to overnutrition causes adipose tissue dysfunction, which is a critical pathological step on the road to type 2 diabetes (T2D) and other metabolic disorders. In this study, we conducted an unbiased investigation into the fundamental molecular mechanisms by which adipocytes transition to an unhealthy state during obesity. Methods We used nuclear tagging and translating ribosome affinity purification (NuTRAP) reporter mice crossed with Adipoq-Cre mice to determine adipocyte-specific 1) transcriptional profiles (RNA-seq), 2) promoter and enhancer activity (H3K27ac ChIP-seq), 3) and PPAR γ cistrome (ChIP-seq) profiles in mice fed chow or a high-fat diet (HFD) for 10 weeks. We also assessed the impact of the PPAR γ agonist rosiglitazone (Rosi) on gene expression and cellular state of adipocytes from the HFD-fed mice. We integrated these data to determine the transcription factors underlying adipocyte responses to HFD and conducted functional studies using shRNA-mediated loss-of-function approaches in 3T3-L1 adipocytes. Results Adipocytes from the HFD-fed mice exhibited reduced expression of adipocyte markers and metabolic genes and enhanced expression of myofibroblast marker genes involved in cytoskeletal organization, accompanied by the formation of actin filament structures within the cell. PPAR γ binding was globally reduced in adipocytes after HFD feeding, and Rosi restored the molecular and cellular phenotypes of adipocytes associated with HFD feeding. We identified the TGFβ1 effector protein SMAD to be enriched at HFD-induced promoters and enhancers and associated with myofibroblast signature genes. TGFβ1 treatment of mature 3T3-L1 adipocytes induced gene expression and cellular changes similar to those seen after HFD in vivo , and knockdown of Smad3 blunted the effects of TGFβ1. Conclusions Our data demonstrate that adipocytes fail to maintain cellular identity after HFD feeding, acquiring characteristics of a myofibroblast-like cell type through reduced PPAR γ activity and elevated TGFβ-SMAD signaling. This cellular identity crisis may be a fundamental mechanism that drives functional decline of adipose tissues during obesity.

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Section: Discussioncontrasting

confidence: 99%

Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFβ-SMAD signaling

Roh

Kumari

Taleb

et al. 2020

Molecular Metabolism

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“…Reversed feeding correspondingly restored cell size, insulin response, expression of F-actin, and its regulatory proteins [143]. Although this study indicated the critical role of actin in adipocyte remodeling, the effect of cytoskeleton on the structure of adipocytes is quite contrary to the findings in other articles [138,144]. Considering that studies listed above used different animal models and/or analyzed different AT depots, different signaling pathways (Akt pathway, Wnt-GSK3β pathway, etc.)…”

Section: Development Of "Supersized" Lipid Dropletcontrasting

confidence: 63%

Adipose Morphology: a Critical Factor in Regulation of Human Metabolic Diseases and Adipose Tissue Dysfunction

Liu

Wang

et al. 2020

OBES SURG

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Emerging evidence highlights that dysfunction of adipose tissue contributes to impaired insulin sensitivity and systemic metabolic deterioration in obese state. Of note, adipocyte hypertrophy serves as a critical event which associates closely with adipose dysfunction. An increase in cell size exacerbates hypoxia and inflammation as well as excessive collagen deposition, finally leading to metabolic dysregulation. Specific mechanisms of adipocyte hypertrophy include dysregulated differentiation and maturation of preadipocytes, enlargement of lipid droplets, and abnormal adipocyte osmolarity sensors. Also, weight loss therapies exert profound influence on adipocyte size. Here, we summarize the critical role of adipocyte hypertrophy in the development of metabolic disturbances. Future studies are required to establish a standard criterion of size measurement to better clarify the impact of adipocyte hypertrophy on changes in metabolic homeostasis.

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“…F-Actin is a filamentous polymer composed of multiple globular actin (G-actin) subunits. The dynamics of the intracellular ratio between F-actin and G-actin are vital for actin remodeling [ 26 , 27 ]. In our experiment, rhodamine phalloidin was used to specifically labeled F-actin, instead of combining it with G-actin.…”

Section: Discussionmentioning

confidence: 99%

Motility and Mechanical Properties of Dendritic Cells Deteriorated by Extracellular Acidosis

Yue

Yang

et al. 2020

Inflammation

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Dendritic cells (DCs) are the most powerful antigen-presenting cells known to date and play an important role in initiating and amplifying both innate and adaptive immune responses. Extracellular acidosis is an important hallmark of a variety of inflammatory processes and solid tumors. However, few studies have focused on the effect of extracellular acidosis on DCs and their functions. Cellular mechanical properties reflect the relationship between cell structure and function, including cytoskeleton (especially F-actin organization), membrane negative charges, membrane fluidity, and osmotic fragility. The study investigated the effects of extracellular acidosis on the DCs functions from the perspective of cellular migration and mechanical properties. The results showed that migration ability, F-actin contents, and membrane negative charges of DCs were reduced by extracellular acidosis no matter whether LPS stimulated its maturation or not. And these functions could not return to normal after removing acidic microenvironment, which revealed that the function impairment induced by extracellular acidosis might be irreversible. In addition, the proliferation capacity of stimulated allogeneic T cells was impaired by extracellular acidosis. Our results suggest extracellular acidosis may play an immunosuppressive role in DCs-mediated immune process.

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During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization

Cited by 37 publications

References 56 publications

Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFβ-SMAD signaling

Adipocytes fail to maintain cellular identity during obesity due to reduced PPARγ activity and elevated TGFβ-SMAD signaling

Adipose Morphology: a Critical Factor in Regulation of Human Metabolic Diseases and Adipose Tissue Dysfunction

Motility and Mechanical Properties of Dendritic Cells Deteriorated by Extracellular Acidosis

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