Adipose tissue is a complex, essential, and highly active metabolic and endocrine organ. Besides adipocytes, adipose tissue contains connective tissue matrix, nerve tissue, stromovascular cells, and immune cells. Together these components function as an integrated unit. Adipose tissue not only responds to afferent signals from traditional hormone systems and the central nervous system but also expresses and secretes factors with important endocrine functions. These factors include leptin, other cytokines, adiponectin, complement components, plasminogen activator inhibitor-1, proteins of the renin-angiotensin system, and resistin. Adipose tissue is also a major site for metabolism of sex steroids and glucocorticoids. The important endocrine function of adipose tissue is emphasized by the adverse metabolic consequences of both adipose tissue excess and deficiency. A better understanding of the endocrine function of adipose tissue will likely lead to more rational therapy for these increasingly prevalent disorders. This review presents an overview of the endocrine functions of adipose tissue.

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Adipose Tissue as an Endocrine Organ

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin - failure to control blood glucose levels results Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention

Mechanisms linking obesity to insulin resistance and type 2 diabetes

Over the last decade, an abundance of evidence has emerged demonstrating a close link between metabolism and immunity. It is now clear that obesity is associated with a state of chronic low-level inflammation. In this article, we discuss the molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes. We also consider mechanisms through which the inflammatory response may be initiated and discuss the reasons for the inflammatory response in obesity. We put forth for consideration some hypotheses regarding important unanswered questions in the field and suggest a model for the integration of inflammatory and metabolic pathways in metabolic disease.

/pdf/inflammation-stress-and-diabetes-121tnz8kqk.pdf

Inflammation, stress, and diabetes

The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.

/pdf/adipokines-in-inflammation-and-metabolic-disease-2i05swlyav.pdf

Adipokines in inflammation and metabolic disease

Adipose tissue as an endocrine organ.

Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes

Suppressors of Cytokine Signaling-1 and -6 Associate with and Inhibit the Insulin Receptor A POTENTIAL MECHANISM FOR CYTOKINE-MEDIATED INSULIN RESISTANCE

Somatomedin-C (SM-C) is a growth hormone-dependent polypeptide with potent mitogenic activity in vivo and in vitro . In the present study, we show that four human breast cell lines maintained in long-term tissue culture (MCF-7, T47-D, MDA-MB-231, and HBL-100) have type I somatomedin receptors and that SM-C stimulates DNA synthesis in these cells. The concentration of SM-C required for half-maximal stimulation of DNA synthesis varied from 0.03 nm in the MCF-7 cell line to 0.6 nm in the T47-D cells. Porcine insulin also stimulated DNA synthesis in all cell lines but, compared to SM-C, 10- to 1000-fold-higher concentrations were required. SM-C receptors on the four breast cell lines were characterized by competitive binding and chemical cross-linking techniques. The four cell lines varied widely in their SM-C binding. In three of the cell lines (MCF-7, MDA-MB-231, and HBL-100), the SM-C receptor had a K d for SM-C of 0.5 to 1 nm, and insulin competed for binding but with a potency 1/10 to 1/100 that of SM-C. In the T47-D cell line, the K d for SM-C binding was 4 nm, and insulin competed poorly for binding. Chemical cross-linking studies showed that all four cell lines have type I somatomedin receptors. Variations in the sensitivity to SM-C and insulin stimulated DNA synthesis in the MCF-7 and T47-D cell lines correlated with type I somatomedin receptor binding by these cells. The data indicate that SM-C is mitogenic for cultured human breast cells and are consistent with the hypothesis that the mitogenic effect of insulin for these cells is mediated through the type I somatomedin receptor.

https://cancerres.aacrjournals.org/content/canres/44/5/2122.full.pdf

Somatomedin-C Receptors and Growth Effects in Human Breast Cells Maintained in Long-Term Tissue Culture

The binding of somatomedin C to serum proteins was investigated using Sephadex G-200 chromatography at pH 7.40. Under these conditions, immunoreactive somatomedin C in whole serum has a Stokes' radius of 43 A (Kd = 0.25). After ammonium sulfate precipitation and DEAE Sephadex chromatography, three protein peaks were obtained. The second peak contained the majority of the immunoreactive somatomedin C, but the somatomedin in this fraction has Stokes' radii of 36 and 14 A (Kd = 0.35 and 0.75, respectively). Recombining this fraction with the DEAE Sephadex peak 3 fraction resulted in the reappearance of the 43 A (Kd = 0.25) species. Chromatography of the 43 A somatomedin C species on Sephadex G-50 in 0.1 M acetic acid-0.15 M NaCl dissociated somatomedin C from its binding protein. The binding protein was recovered in the void volume fractions of the G-50 column. This acid-treated binding protein had a Stokes' radius of 36 A (Kd = 0.35), as determined by the binding of [l25I]somatomedin C at pH 7.40. When the ...

Richard W. Furlanetto

Papers

Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes

Suppressors of Cytokine Signaling-1 and -6 Associate with and Inhibit the Insulin Receptor A POTENTIAL MECHANISM FOR CYTOKINE-MEDIATED INSULIN RESISTANCE

Somatomedin-C Receptors and Growth Effects in Human Breast Cells Maintained in Long-Term Tissue Culture

The Somatomedin C Binding Protein: Evidence for a Heterologous Subunit Structure*

Interaction of Human Suppressor of Cytokine Signaling (SOCS)-2 with the Insulin-like Growth Factor-I Receptor