Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies

Shetty, Shoba; Kusminski, Christine M.; Scherer, Philipp E.

doi:10.1016/j.tips.2009.02.004

Cited by 190 publications

(165 citation statements)

References 75 publications

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“…17,18 Unlike other adipokines that increase with weight gain, serum adiponectin is inversely correlated with obesity. Low adiponectin has been correlated with albuminuria in both mice and humans, and obesity (and, therefore, low adiponectin) may be causative in some patients with FSGS.…”

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confidence: 99%

Adiponectin Promotes Functional Recovery after Podocyte Ablation

Rutkowski

Wang²,

Park

et al. 2013

Journal of the American Society of Nephrology

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133

115

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Low levels of the adipocyte-secreted protein adiponectin correlate with albuminuria in both mice and humans, but whether adiponectin has a causative role in modulating renal disease is unknown. Here, we first generated a mouse model that allows induction of caspase-8-mediated apoptosis specifically in podocytes upon injection of a construct-specific agent. These POD-ATTAC mice exhibited significant kidney damage, mimicking aspects of human renal disease, such as foot process effacement, mesangial expansion, and glomerulosclerosis. After the initial induction, both podocytes and filtration function recovered. Next, we crossed POD-ATTAC mice with mice lacking or overexpressing adiponectin. POD-ATTAC mice lacking adiponectin developed irreversible albuminuria and renal failure; conversely, POD-ATTAC mice overexpressing adiponectin recovered more rapidly and exhibited less interstitial fibrosis. In conclusion, these results suggest that adiponectin is a renoprotective protein after podocyte injury. Furthermore, the POD-ATTAC mouse provides a platform for further studies, allowing precise timing of podocyte injury and regeneration.

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confidence: 99%

Adiponectin Promotes Functional Recovery after Podocyte Ablation

Rutkowski

Wang²,

Park

et al. 2013

Journal of the American Society of Nephrology

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133

115

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“…4 Adiponectin has been suggested to play an important role in the pathogenesis of liver fibrosis. [7][8][9][10][11][12][13][14][15] Notably, in addition to adipose tissue, adiponectin is expressed in stellate cells. 16 Previous studies have shown that adiponectin has important effects specifically on stellate cells, and the mechanism of these effects remains an area of active investigation.…”

mentioning

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

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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.

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“…It has been discovered that humans contain both white and brown adipose tissue which possess two distinct developmental origins and functions [38][39][40][41][42] . The brown adipose tissue has yet to be studied in humans with SCI; however, its potential contribution to increase the metabolic rate is important considering the prevalence of obesity after SCI.…”

Section: White Vs Brown Adipose Tissuementioning

confidence: 99%

“…Leptin is positively associated with white adipose tissue and serves to suppress food intake and increase energy expenditure [2] . The hormone adiponectin is inversely correlated with white adipose tissue and has been considered a promising biomarker for the indication of insulin sensitivity [2,39] . In addition to these secreting hormones, white adipose tissue can also secrete proinflammatory factors including tumor necrosis factor alpha, interleukin-6, and monocyte chemotactic protein-1 [2] .…”

Section: White Adipose Tissuementioning

confidence: 99%

“…In addition to these secreting hormones, white adipose tissue can also secrete proinflammatory factors including tumor necrosis factor alpha, interleukin-6, and monocyte chemotactic protein-1 [2] . The various adipose tissue compartments, such as subcutaneous and visceral depots follow a distinct pattern of hormone and adipokine secretion [39] . The adipocytes in subcutaneous depots have a higher capacity for adipogenesis and differentiate more rapidly compared to visceral depots.…”

Section: White Adipose Tissuementioning

confidence: 99%

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Adiposity and spinal cord injury

Gorgey¹

2015

WJO

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The drastic changes in body composition following spinal cord injury (SCI) have been shown to play a significant role in cardiovascular and metabolic health. The pattern of storage and distribution of different types of adipose tissue may impact metabolic health variables similar to carbohydrate, lipid and bone metabolism. The use of magnetic resonance imaging provides insights on the interplay among different regional adipose tissue compartments and their role in developing chronic diseases. Regional adipose tissue can be either distributed centrally or peripherally into subcutaneous and ectopic sites. The primary ectopic adipose tissue sites are visceral, intramuscular and bone marrow. Dysfunction in the central nervous system following SCI impacts the pattern of distribution of adiposity especially between tetraplegia and paraplegia. The current editorial is focused primarily on introducing different types of adipose tissue and establishing scientific basis to develop appropriate dietary, rehabilitation or pharmaceutical interventions to manage the negative consequences of increasing adiposity after SCI. We have also summarized the clinical implications and future recommendations relevant to study adiposity after SCI.

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Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies

Cited by 190 publications

References 75 publications

Adiponectin Promotes Functional Recovery after Podocyte Ablation

Adiponectin Promotes Functional Recovery after Podocyte Ablation

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

Adiposity and spinal cord injury

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