Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity

Bell, Lauren N.; Ward, Jennifer L.; Degawa-Yamauchi, Mikako; Bovenkerk, Jason E.; Jones, Rose Marie; Cacucci, Brenda; Gupta, Christine E.; Sheridan, Carol; Sheridan, Kevin; Shankar, Sudha; Steinberg, Helmut O.; March, Keith L.; Considine, Robert V.

doi:10.1152/ajpendo.00174.2006

Cited by 102 publications

(82 citation statements)

References 35 publications

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“…32,33 Furthermore, high levels of HGF expression were found in white adipose tissue. 4,34 There are no data, however, concerning the contribution of a specific adipose tissue depot in the production of HGF. The current results indicate that specifically VAT, may have a contribution to HGF concentrations.…”

Section: Discussionmentioning

confidence: 99%

Adipose tissue quantity and composition contribute to adipokine concentrations in the subclavian vein and the inferior mesenteric vein

et al. 2011

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BACKGROUND: Adipose tissue dysfunction is associated with inflammation, type 2 diabetes mellitus and vascular diseases. Visceral adipose tissue (VAT)-derived adipokines, which are released in the portal circulation may influence liver metabolism. OBJECTIVES: (1) To estimate the contribution of VAT and subcutaneous adipose tissue (SAT) on adipokine levels by measuring differences in adipokine concentrations between the portal draining inferior mesenteric vein and the subclavian vein.(2) To determine the relation of both VAT and SAT quantity and composition to mesenteric and systemic concentrations of adipokines. DESIGN: Cross-sectional cohort study. SUBJECTS: A total of 32 patients undergoing abdominal aortic surgery. MEASUREMENTS: A panel of 18 adipokines was measured in perioperatively obtained blood samples from the subclavian vein and the inferior mesenteric vein. Adipocyte size, macrophage infiltration and capillary density were measured in subcutaneous and mesenteric adipose tissue biopsies; SAT and VAT areas were measured on computed tomography images. RESULTS: Serum interferon-g-inducible protein 10 (IP-10) and hepatocyte growth factor (HGF) concentrations were significantly higher in the inferior mesenteric vein vs the subclavian vein. SAT area (b --18; 95% confidence interval (CI) À35 to À2), subcutaneous adipocyte size (b --488; 95% CI À938 to À38) and SAT macrophages quantity (b --1439; 95% CI À2387 to À491) were negatively associated with adiponectin levels in the systemic circulation. SAT area was related to systemic concentrations of leptin. Mesenteric adiponectin concentrations were related to VAT area (b --20; 95% CI À35 to À5) and visceral adipocyte size (b À1076; 95% CI À1624 to À527). VAT area, adipocyte size and capillary density were related to systemic adiponectin concentrations. CONCLUSION: SAT and VAT quantities as well as morphologic characteristics of both adipose tissue depots are related to systemic and mesenteric adipokine concentrations. There were no differences in adipokine concentrations between the mesenteric and subclavian vein, except for higher IP-10 and HGF concentrations in the inferior mesenteric vein, indicating a possible contribution of VAT to IP-10 and HGF levels.

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Section: Discussionmentioning

confidence: 99%

Adipose tissue quantity and composition contribute to adipokine concentrations in the subclavian vein and the inferior mesenteric vein

et al. 2011

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“…Leptin can stimulate the critical steps required to evoke an angiogenic program (69). In addition, bFGF can promote vascular endothelial cell growth (70) and hence the process of angiogenesis. Of note, bFGF is secreted by preadipocytes, and its levels are increased during caloric excess.…”

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

confidence: 99%

Adipose tissue remodeling and obesity

Sun¹,

Kusminski²,

Scherer³

2011

J. Clin. Invest.

1,552

1,381

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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.

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“…Fibroblast growth factor-2 (FGF-2) and fibroblast growth factor-10 (FGF-10) are also potent inducers of angiogenesis secreted by adipocytes [13,14,26]. Hepatocyte growth factor (HGF) is also secreted by adipocytes and stimulates angiogenesis [3,39]. Leptin is a major adipocytokine which plays a crucial role in the regulation of appetite and energy metabolism [6,16,33].…”

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confidence: 99%

Fat Depot-Specific Differences in Angiogenic Growth Factor Gene Expression and Its Relation to Adipocyte Size in Cattle

Yamada

Kawakami

Nakanishi

2010

The Journal of Veterinary Medical Science

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ABSTRACT. Adipocytes derived from different anatomical sites vary in the expression of adipocytokines and growth factor genes. Adipogenesis is tightly associated with angiogenesis, although the regional variation of angiogenic growth factor gene expression in adipose tissues remains unclear. In this experiment, we studied the fat depot-specific differences (subcutaneous, intramuscular, intermuscular, renal, and mesenteric) in the expression of angiogenic growth factor mRNA [vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), fibroblast growth factor-10 (FGF-10), hepatocyte growth factor (HGF), and leptin], as well as the relationship between angiogenic growth factor mRNA level and adipocyte size in bovine adipose tissues. Intermuscular, renal, and mesenteric adipose tissues expressed significantly higher VEGF, FGF-2, and leptin mRNA levels than did subcutaneous and intramuscular adipose tissues. Mesenteric adipose tissue also expressed higher FGF-10 mRNA levels than did subcutaneous and intramuscular adipose tissues. There was no significant difference in the expression of HGF mRNA among adipose tissue depots. A significant correlation existed between adipocyte size and VEGF, FGF-2, FGF-10, and leptin mRNA levels. These results indicate that fat depot-specific difference in angiogenic growth factor gene expression results from the difference in adipocyte size.

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Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity

Cited by 102 publications

References 35 publications

Adipose tissue quantity and composition contribute to adipokine concentrations in the subclavian vein and the inferior mesenteric vein

Adipose tissue quantity and composition contribute to adipokine concentrations in the subclavian vein and the inferior mesenteric vein

Adipose tissue remodeling and obesity

Fat Depot-Specific Differences in Angiogenic Growth Factor Gene Expression and Its Relation to Adipocyte Size in Cattle

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