Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue

Honecker, Julius; Ruschke, Stefan; Seeliger, Claudine; Laber, Samantha; Strobel, Sophie; Pröll, Priska; Nellåker, Christoffer; Lindgren, Cecilia M.; Kulozik, Ulrich; Ecker, Josef; Karampinos, Dimitrios C.; Claussnitzer, Melina; Hauner, Hans

doi:10.1016/j.ebiom.2022.104020

Cited by 28 publications

(17 citation statements)

References 63 publications

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“…The increased percentage of larger adipocytes in the gonadal fat was accompanied by down-regulation of Ttc36 and up-regulation of Arhgdig (Fig. 5i), genes recently identified as markers of visceral fat adipocyte hypertrophy in human 32 . However, the increased adipocyte size was not explained by an intrinsic increase in expression of lipid transporters, (Extended Data Fig.…”

Section: Resultsmentioning

confidence: 82%

The imprinted Mir483 is a growth suppressor and metabolic regulator functioning through IGF1

Sandovici

Fernandez‐Twinn

Campbell

et al. 2022

Preprint

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Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Here, we uncover the control mechanisms and physiological functions of Mir483 in vivo, by generating constitutive loss-of-function and over-expressing mice. Mir483 expression is imprinted and dependent on the Igf2 promoters and Igf2/H19 imprinting control region. Over-expression of Mir483 causes severe mid-gestation fetal, but not placental, growth restriction, and late lethality. Fetal death is prevented by restoring Mir483 to endogenous levels using an inducible transgenic system. Continuous postnatal Mir483 over-expression induces growth stunting, elevated hepatic lipid content, increased adiposity, reduced local and systemic IGF1 levels and increased GH. The growth phenotypes are rescued by IGF1 infusion. Our findings provide evidence for a novel functional antagonism between a growth-suppressor microRNA and its growth-promoter host gene, and suggest that Mir483 evolved to limit excessive tissue growth through repression of IGF ligand signalling.

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Section: Resultsmentioning

confidence: 82%

The imprinted Mir483 is a growth suppressor and metabolic regulator functioning through IGF1

Sandovici

Fernandez‐Twinn

Campbell

et al. 2022

Preprint

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“… 3 , 28 , 29 In line with this, reduced adipose tissue CDO1 mRNA was observed in genetic- and diet-induced obesity mice models 4 and in human visceral adipose tissue from morbidly obese subjects (current study). Considering that expression of adipogenic genes in adipose tissue is also decreased in morbid obesity, as consequence of obesity-associated adipose tissue dysfunction, 12 , 30 , 31 , 32 , 33 the positive correlation between mRNA expression of CDO1 and adipogenic genes would be in consonance with the anti-obesity effects of CDO1 activity. In addition, CDO1 gene knockdown in human adipocyte precursor cells impairs mitochondrial respiration, a relevant process in adipogenesis and adipocyte function.…”

Section: Discussionmentioning

confidence: 95%

Adipose tissue cysteine dioxygenase type 1 is associated with an anti-inflammatory profile, impacting on systemic metabolic traits

Latorre¹,

Mayneris‐Perxachs²,

Oliveras-Cañellas³

et al. 2022

eBioMedicine

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“…Increased fat cell number (hyperplastic expansion) generates new small-sized adipocytes and is considered to offer a healthy mechanism of adipose tissue expansion ( Vishvanath and Gupta, 2019 ). Considerable enlargement of cell size (hypertrophic expansion), however, leads to adipocyte dysfunction and has been widely recognized as the primary factor in the development of obesity-related metabolic syndrome ( Weyer et al, 2000 ; Skurk et al, 2007 ; Laforest et al, 2015 ; Suarez-Cuenca et al, 2021 ; Honecker et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The regulation of adipocyte growth in white adipose tissue

Spalding

2022

Front. Cell Dev. Biol.

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Adipocytes can increase in volume up to a thousand-fold, storing excess calories as triacylglycerol in large lipid droplets. The dramatic morphological changes required of adipocytes demands extensive cytoskeletal remodeling, including lipid droplet and plasma membrane expansion. Cell growth-related signalling pathways are activated, stimulating the production of sufficient amino acids, functional lipids and nucleotides to meet the increasing cellular needs of lipid storage, metabolic activity and adipokine secretion. Continued expansion gives rise to enlarged (hypertrophic) adipocytes. This can result in a failure to maintain growth-related homeostasis and an inability to cope with excess nutrition or respond to stimuli efficiently, ultimately leading to metabolic dysfunction. We summarize recent studies which investigate the functional and cellular structure remodeling of hypertrophic adipocytes. How adipocytes adapt to an enlarged cell size and how this relates to cellular dysfunction are discussed. Understanding the healthy and pathological processes involved in adipocyte hypertrophy may shed light on new strategies for promoting healthy adipose tissue expansion.

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Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue

Cited by 28 publications

References 63 publications

The imprinted Mir483 is a growth suppressor and metabolic regulator functioning through IGF1

The imprinted Mir483 is a growth suppressor and metabolic regulator functioning through IGF1

Adipose tissue cysteine dioxygenase type 1 is associated with an anti-inflammatory profile, impacting on systemic metabolic traits

The regulation of adipocyte growth in white adipose tissue

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