Cellular models for understanding adipogenesis, adipose dysfunction, and obesity

Armani, Andrea M.; Mammi, Caterina; Marzolla, Vincenzo; Calanchini, Matilde; Antelmi, Antonella; Rosano, Giuseppe M.C.; Fabbri, Andrea; Caprio, Massimiliano

doi:10.1002/jcb.22598

Cited by 141 publications

(110 citation statements)

References 82 publications

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“…For example, preadipocytes are known to be particularly vulnerable to age-related changes in gene expression compared with mature adipocytes (1,9,10,28,60). Our studies indicate that the microenvironment where vulnerable cells (preadipocytes) are located, within the aging adipose tissue, may have dramatic effects on the ultimate long-term function of individual cells.…”

Section: Discussionmentioning

confidence: 75%

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Zhang

Ebenezer

Dasuri

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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As a part of aging there are known to be numerous alterations which occur in multiple tissues of the body, and the focus of this study was to determine the extent to which oxidative stress and hypoxia occur during adipose tissue aging. In our studies we demonstrate for the first time that aging is associated with both hypoxia (38% reduction in oxygen levels, Po2 21.7 mmHg) and increases reactive oxygen species in visceral fat depots of aging male C57Bl/6 mice. Interestingly, aging visceral fat depots were observed to have significantly less change in the expression of genes involved in redox regulation compared with aging subcutaneous fat tissue. Exposure of 3T3-L1 adipocytes to the levels of hypoxia observed in aging adipose tissue was sufficient to alter multiple aspects of adipose biology inducing increased levels of in insulin-stimulated glucose uptake and decreased lipid content. Taken together, these data demonstrate that hypoxia and increased levels of reactive oxygen species occur in aging adipose tissue, highlighting the potential for these two stressors as potential modulators of adipose dysfunction during aging.

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Section: Discussionmentioning

confidence: 75%

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Zhang

Ebenezer

Dasuri

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…Among the adipogenic factors commonly used in the induction of adipogenesis in vitro, insulin promotes the adipose conversion process through activation of AKT protein kinase (Cho et al 2004, Armani et al 2010. Notably, ectopic expression of activated AKT is able to induce differentiation of 3T3L1 preadipocytes (Gagnon et al 1999) and, in mice, disruption of insulin signaling in adipose tissue leads to reduced fat mass (Bluher et al 2002).…”

Section: Role Of Mr In Regulating Adipogenesis-linked Signaling Pathwaysmentioning

confidence: 99%

Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

Armani¹,

Marzolla²,

Fabbri³

et al. 2015

Journal of Molecular Endocrinology

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In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity.

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“…Adipogenesis is a multistep process that is regulated by several transcription factors and hormones, whereby the precursor cells (pre-adipocytes) differentiate into mature adipocytes [7]. In this process, committed pre-adipocytes present in the stromal vascular fraction (SVF) of the AT pad express the transcriptional regulator of pre-adipocyte determination, Zfp423 [8].…”

Section: Introductionmentioning

confidence: 99%

Excess fructose intake‐induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals

et al. 2013

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We studied the effect of feeding normal adult male rats with a commercial diet supplemented with fructose added to the drinking water (10% w/v; fructose-rich diet, FRD) on the adipogenic capacity of stromal-vascular fraction (SVF) cells isolated from visceral adipose tissue (VAT) pads. Animals received either the commercial diet or FRD ad libitum for 3 weeks; thereafter, we evaluated the in vitro proliferative and adipogenic capacities of their VAT SVF cells. FRD significantly increased plasma insulin, triglyceride and leptin levels, VAT mass/cell size, and the in vitro adipogenic capacity of SVF cells. Flow cytometry studies indicated that the VAT precursor cell population number did not differ between groups; however, the accelerated adipogenic process could result from an imbalance between endogenous pro-and anti-adipogenic SVF cell signals, which are clearly shifted towards the former. The increased insulin milieu and its intracellular mediator (insulin receptor substrate-1) in VAT pads, as well as the enhanced SVF cell expression of Zpf423 and peroxisome proliferator receptor-c2 (all pro-adipogenic modulators), together with a decreased SVF cell concentration of anti-adipogenic factors (pre-adipocyte factor-1 and wingless-type MMTV-10b), strongly supports this assumption. We hypothesize that the VAT mass expansion recorded in FRD rats results from the combination of initial accelerated adipogenesis and final cell hypertrophy. It remains to be determined whether FRD administration over longer periods could perpetuate both processes, or whether cell hypertrophy itself remains responsible for a further VAT mass expansion, as observed in advanced/morbid obesity.

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Cellular models for understanding adipogenesis, adipose dysfunction, and obesity

Cited by 141 publications

References 82 publications

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

Excess fructose intake‐induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals

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