Obesity-associated improvements in metabolic profile through expansion of adipose tissue

Kim, Ja Young; Wall, Esther van de; Laplante, Mathieu; Azzara, Anthony V.; Trujillo, María E.; Hofmann, Susanna M.; Schraw, Todd; Durand, J; Li, Hua; Li, Guangyu; Jelicks, Linda A.; Mehler, Mark F.; Hui, David Y.; Deshaies, Yves; Shulman, Gerald I.; Schwartz, Gary J.; Scherer, Philipp E.

doi:10.1172/jci31021

Cited by 1,141 publications

(1,066 citation statements)

References 64 publications

Supporting

Mentioning

976

Contrasting

Unclassified

Order By: Relevance

“…Adiponectin, for example, has been shown to induce angiogenesis in hypoxic fat pads and tumors (75,91). Moreover, we have previously demonstrated that overexpression of adiponectin in an ob/ob background improves vascularization and expansion of the subcutaneous fat pad in particular (91).…”

Section: Angiogenesis a Rate-limiting Step For At Expansion And Remomentioning

confidence: 89%

Adipose tissue remodeling and obesity

Sun¹,

Kusminski²,

Scherer³

2011

J. Clin. Invest.

Self Cite

1,489

1,309

View full text Add to dashboard Cite

To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth. IntroductionAdipose tissue (AT) can respond rapidly and dynamically to alterations in nutrient deprivation and excess through adipocyte hypertrophy and hyperplasia, thereby fulfilling its major role in wholebody energy homeostasis. AT remodeling is an ongoing process that is pathologically accelerated in the obese state, and thus, features such as reduced angiogenic remodeling, ECM overproduction, a heightened state of immune cell infiltration and subsequent proinflammatory responses prevail in many obese fat-pads (1). However, not all AT expansion is necessarily associated with pathological changes. The concept of the "metabolically healthy obese" state (2) suggests that some individuals can preserve systemic insulin sensitivity on the basis of "healthy" AT expansion, bypassing all of the aforementioned pathological consequences associated with obesity (3), thereby also avoiding the obesity-associated lipotoxic side effects. Many physiologically relevant processes important for human AT remodeling can be studied in rodent models, with the added advantage that processes related to AT expansion and reduction can occur at an extremely rapid rate. A 24-hour fast in a mouse is associated with a dramatic loss of AT mass and an acute remodeling process that involves rapid infiltration of macrophages; moreover, merely 24 to 48 hours of exposure to a high-fat diet (HFD) can cause a prompt increase in adipocyte size (4). AT is therefore an ideal model system to study rapid alterations in tissue expansion and reduction, as it adapts to a differential nutrient supply. Here, we will focus on key aspects of the intricate dynamics of AT remodeling and subsequent inflammatory consequences that arise from obesity.

show abstract

Section: Angiogenesis a Rate-limiting Step For At Expansion And Remomentioning

confidence: 89%

Adipose tissue remodeling and obesity

Sun¹,

Kusminski²,

Scherer³

2011

J. Clin. Invest.

Self Cite

1,489

1,309

View full text Add to dashboard Cite

show abstract

“…Studies from our laboratory have shown that overexpression of adiponectin in a leptindeficient mouse model improves the metabolic phenotype but at the expense of a twofold increase in body weight and massive enlargement of the subcutaneous adipose mass. 33 Although it is very likely that adiponectin inhibits the profibrotic effects of leptin, the mechanisms underlying this process are not clear.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

Shafiei

Shetty

Scherer

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

In this study, we elucidated the mechanism by which adiponectin modulates hepatic stellate cell activation and fibrogenesis. Adiponectin-overexpressing transgenic mice receiving thioacetamide were resistant to fibrosis, compared with controls. In contrast, adiponectin-null animals developed severe fibrosis. Expression of collagen ␣1(I) and ␣-smooth muscle actin (␣-SMA) mRNAs were significantly lower in adiponectin-overexpressing mice, compared with controls. In wild-type stellate cells exposed to a lentivirus encoding adiponectin, expression of peroxisome proliferator-activated receptor-␥ (PPAR␥), SREBP1c, and CEBP␣ mRNAs was significantly increased (3.2-, 4.1-, and 2.2-fold, respectively; n ‫؍‬ 3; P < 0.05, adiponectin virus versus control), consistent with possible activation of an adipogenic transcriptional program. Troglitazone, a PPAR␥ agonist, strongly suppressed upregulation of collagen ␣1(I) and ␣-SMA mRNA in stellate cells isolated from wild-type mice; however, stellate cells from adiponectin-null animals failed to respond to troglitazone. Furthermore, in isolated stellate cells in which PPAR␥ was depleted using an adenovirus-Cre-recombinase system and in which adiponectin was also overexpressed, collagen ␣1(I) and ␣-SMA were significantly inhibited. We conclude that the PPAR␥ effect on stellate cell activation and the fibrogenic cascade appears to be adiponectin-dependent; however, the inhibitory effect of adiponectin on stellate cell activation was not dependent on PPAR␥, suggesting the presence of PPAR␥-dependent as well as independent pathways in stellate cells.

show abstract

“…A mouse model with chronic overexpression of adiponectin have an enormous increase in subcutaneous fat mass; however, they were protected against dietinduced insulin resistance (Kim et al 2007). The interpretation is that an increase in AT storage capacity may prevent metabolic complications.…”

Section: Adipose Tissue Expansionmentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

296

172

View full text Add to dashboard Cite

Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

show abstract

Obesity-associated improvements in metabolic profile through expansion of adipose tissue

Cited by 1,141 publications

References 64 publications

Adipose tissue remodeling and obesity

Adipose tissue remodeling and obesity

Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

Obesity and related consequences to ageing

Contact Info

Product

Resources

About